Search

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor's professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Chronic obstructive pulmonary disease (COPD) is a complex heterogeneous chronic respiratory disease and third leading cause of death worldwide. In addition to damage to the respiratory system, COPD has significant extra-pulmonary effects, of which skeletal muscle dysfunction is one of the most prominent. Skeletal muscle dysfunction in COPD can manifest as impaired muscle strength, loss of muscle mass, or decreased endurance, etc . Possible pathogenic mechanisms include abnormal neuro-muscular stimulation, dysregulated protein synthesis, hypoxia, inflammation, oxidative stress, mitochondrial dysfunction, impaired regenerative capacity, etc . Pulmonary rehabilitation (PR) can improve limb muscle function, exercise tolerance and quality of life of COPD patients. Exercise training is usually the main component of any PR program. Currently, PR is the main intervention for skeletal muscle dysfunction in COPD and could be executed in PR center, at home, or in the community using state-of-the-art technology. In this review, we summarized recent advances in pathogenic mechanisms and pulmonary rehabilitation strategies for skeletal muscle dysfunction in COPD, in particular exercise training protocols, respiratory support and feedback in PR, and so on.

In the context of delayed marriage and parenthood, decreased willingness in having children, and population aging in China, maternal and child health has become an important and urgent issue. Being essential platforms for research in maternal and child health, the importance of birth cohorts has been widely recognized. In the past 20 years, tens of birth cohorts have been established in major cities and regions of China, with cohorts ranging from thousands to hundreds of thousands. These cohorts, particularly those large ones launched in recent years, have collected a wide spectrum of data and biological samples from mothers and children. Although they have made considerable preliminary achievements, there remain difficulties and challenges. The significant challenges include small and medium-sized cohorts' lacking of clear research themes; insufficient recognition of and emphasis on behavioral and social determinants of health while emphasizing biological determinants of health; variations in types of variables and quality of data collected, which make it difficult for cohorts to be merged and shared; lack of and difficulties in long-term follow-up; significant uncertainties in resources for long-term sustention of the cohorts, and so on. So, we argue that birth cohorts should focus on essential and urgent issues in maternal and child health in the country and seek recognition and support from the government and the entire society. Last but not least, the overall success of birth cohorts in the country requires scientists to be not only academically capable, but also realistic, persistent, altruistic, and collaborative.

Objective: To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway., Methods: NIH-3T3 cells were treated with quercetin or MCC950 (a specific inhibitor of NLRP3) before stimulation with lipopolysaccharide (LPS) and ATP to induce cell pyroptosis. The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times. Morphological changes of the treated cells was observed, and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA; the protein expressions of NLRP3, cleaved caspase-1, and GSDMD-N and the mRNA levels of NLRP3, caspase-1 and GSDMD were detected using Western blotting and qRT-PCR. The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay., Results: The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results. LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling, cell membrane rupture and leakage of cell contents, significantly increased IL-18 and IL-1β levels, and enhanced protein expressions of NLRP3, cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3, caspase-1 and GSDMD. LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells. Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP, lowered the concentrations of IL-18 and IL-1β, decreased the expression levels of NLRP3, caspase-1/cleaved caspase-1, GSDMD/GSDMD-N, and reduced the number of TUNEL-positive cells and LDH release., Conclusion: Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Objective: To investigate the improvement effects and mechanisms of composite chitosan (CS) hydrogel on traditional polypropylene (PP) mesh for repairing abdominal wall defects., Methods: CS hydrogel was prepared via physical cross-linking and then combined with PP mesh to create a CS hydrogel/PP mesh composite. The internal structure and hydrophilicity of the composite were characterized using macroscopic observation, upright metallographic microscope, scanning electron microscopy, and water contact angle measurements. The performance of the composite (experimental group) in resisting cell adhesion and supporting cell infiltration was assessed through fibroblast (NIH-3T3) infiltration experiments and human umbilical vein endothelial cells (HUVECs) tube formation assays, and simple cells were used as control group. Finally, a bilateral abdominal wall defect model (1.5 cm×1.0 cm) was established in 18 Sprague Dawley rats aged 8-10 weeks, with the composite used on one side (experimental group) and PP mesh on the other side (control group). The effects on promoting wound healing, preventing adhesion, angiogenesis, and anti-inflammation were investigated through macroscopic observation, histological staining (HE and Masson staining), and immunohistochemical staining (CD31, CD68)., Results: The composite appeared as a pale yellow, transparent solid with a thickness of 2-3 mm, with the PP mesh securely encapsulated within the hydrogel. Scanning electron microscopy revealed that the hydrogel contained interconnected pores measuring 100-300 μm, forming a porous structure. Contact angle measurements indicated that CS hydrogel exhibited good hydrophilicity, while PP mesh was highly hydrophobic. In vitro cell culture experiments showed that DAPI staining indicated fewer positive cells in the experimental group after 1 day of culture, while the cells in control group covered the entire well plate. After 3 days of culture, the cells in experimental group were spherical and displayed uneven fluorescence, suggesting that the material could reduce cell adhesion while supporting cell infiltration. HUVECs tube formation experiments demonstrated an increase in cell numbers in experimental group with a trend towards tube formation, while cells in control group were sparsely distributed and showed no migration. In the rat abdominal wall defect repair experiment, results showed that after 1 week post-surgery, the experimental group had tissue and blood vessels infiltrating, and by 4 weeks, the integrity was well restored with significant regeneration of muscle and blood vessels, while the control group exhibited adhesions and incomplete healing. HE staining results indicated weaker cell infiltration in the experimental group, with cell density significantly higher than that of the control group at 2 and 4 weeks post-surgery ( P <0.05). Masson staining revealed that collagen fibers in the experimental group were arranged neatly, with significantly increased collagen content at 2 weeks post-surgery ( P <0.05), while collagen content was similar in both groups at 4 weeks ( P> 0.05). Immunohistochemical staining showed that CD31-positive cells were evenly distributed between muscle layers in the experimental group, whereas the control group exhibited notable defects. At 2 weeks after operation, the CD31-positive cell ratio was significantly higher than that in the control group ( P <0.05); at 2 and 4 weeks after operation, the CD68-positive cell ratio in the experimental group was significantly lower than that in the control group ( P <0.05)., Conclusion: CS hydrogel has a positive effect on preventing adhesions and promoting wound healing, exhibiting anti-inflammatory and pro-angiogenic properties during the healing process. This provides a promising strategy to address challenges related to abdominal adhesions and reconstruction.

Objective: To clarify the key outcomes of acupuncture-moxibustion treatment of ulcerative colitis., Methods: The clinical randomized controlled trials (RCTs) for ulcerative colitis treated with acupuncture and moxibustion were searched from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, from the inception of each database to March 20th, 2023. The basic information of literature, intervention measures and outcome indexes were collected. The selection of primary and secondary outcomes, the use frequency of each index and the combination of them in utility were analyzed; and index domains of acupuncture and moxibustion for ulcerative colitis were summarized., Results: A total of 215 RCTs were included and 54 outcomes were involved, classified into 6 categories, i.e. TCM syndromes, symptoms/physical signs, physical and chemical tests, quality of life, long-term prognosis and safety events. The top 3 outcomes with high use frequency were clinical effect evaluation, adverse reactions of acupuncture and moxibustion and the score of main symptoms. Only 3 articles clearly reported the primary outcome and the secondary ones, 180 articles used two types of outcomes simultaneously, 3 articles clearly described the time points of the observation indexes, and 126 articles determined the sources of the evaluation criteria of therapeutic effect, with 57 criteria involved., Conclusion: At present, the outcomes have not been standardized in RCTs of acupuncture and moxibustion for ulcerative colitis. It needs to clarify the primary one and the secondary ones. The criteria have not been unified for the evaluation of therapeutic effects and there is less consideration on the quality of life in patients, the follow-up visit and safety events. The attention should be paid to develop the outcome set, in which, the endoscopic score is taken as the objective, and the improvements in the symptoms/physical signs and the biochemical examination as the supplementary.

A large number of studies have confirmed the anti-inflammatory effects of acupuncture, and some of the mechanisms and pathways regulating inflammatory response have been revealed. However, most of these researches focused on the effect of acupuncture on systemic anti-inflammation, and there is no consensus about the effect characteristics of different acupoints on regulating inflammatory response. It is noteworthy that increasing attention and exploration have been paid to the neuro-immune interactions and regulation of immune-inflammatory homeostasis. Importantly, the understanding of local neuroimmune regulation of non-immune organs has been deepening, which was known as the regional immunity. This new concept lays a scientific foundation for elucidating the characteristics of acupoints on the inflammation, especially the modulation of target visceral organs by the relevant acupoint stimulation. In this paper, the local effects (e.g. activating regional nerve components to induce local neuroimmuno-inflammatory regulation, etc), target visceral organ effects (e.g. regulating activities of visceral resident immune cells to initiate regional immunity regulation mediated by locally resident lymphocytes to promote inflammatory response degradation and to restore the homeostasis of regional immunity in the internal organs, via somato-visceral neuro-segmental connection, etc.) and systemic anti-inflammatory effects (e.g. regulating cholinergic anti-inflammatory pathway, including activating the vagus nerve to exert systemic anti-inflammatory effects through neuroimmune regulatory network, etc.) of acupoint stimulation were analyzed from different levels of neuroimmunological regulation, so as to provide new insights for clarifying the role of acupoints in improving inflammatory diseases.

Objective: To investigate the clinical features and genetic variant of a child with West syndrome due to a variant of NEXMIF gene., Methods: A child who was admitted to the First Medical Center of Chinese PLA General Hospital in March 2021 was selected as the study subject. Clinical data of the patient was collected. The child and his parents were subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and pathogenicity analysis., Results: The child, a 4-month-old boy, had presented with spastic seizures with no obvious cause. Abnormal EEG, severe hypsarrhythmia, and multiple spastic seizures were discovered. Cranial MRI revealed widening of the extracerebral space at the top of the frontal lobe. Physical examination revealed that the child could not hold his head up, and could not respond to sounds or follow objects with his eyes. He also has microcephaly, with height < 1 s. The child was diagnosed with West syndrome at a local hospital, and was given prednisone orally for 3 months, with seizures under control. Topiramate tablets were taken orally for maintenance treatment, and he has been seizure-free for 7 months. DNA sequencing revealed that he has harbored a de novo nonsense variant of c.982&#95;c.983delTT (p.L328Dfs*23) in the NEXMIF gene., Conclusion: For children with West syndrome with severe developmental delay or even regression as the first symptoms, uncontrollable seizures and abnormal facial appearance, mutations of the NEXMIF gene should be suspected, and genetic testing can facilitate early diagnosis and treatment.

Objectives: The drug-resistant genes carried by carbapenem-resistant Klebsiella pneumoniae (CRKP) limit clinical treatment options, and its virulence genes severely affect patient prognosis. This study aims to investigate the distribution of virulence genes, capsular serotypes, and molecular epidemiological characteristics of CRKP in ICU, to understand the characteristics of CRKP infections in ICU, and to provide a scientific basis for effective monitoring and control of CRKP infections in ICU., Methods: A total of 40 non-duplicate strains of CRKP isolated from the ICU of Guangdong Provincial People's Hospital between January 2021 and December 2022 were collected and analyzed. Whole-genome sequencing was used to analyze the distribution of resistance genes, virulence genes, and capsular serotypes of the strains. The sequences of 7 housekeeping genes of CRKP genome were uploaded to the Klebsiella pneumoniae (KPN)multilocus sequence typing (MLST) database to determine the sequence types (STs) of the strains., Results: The age of the 40 ICU CRKP-infected patients was (69.03±17.82) years old, with various underlying diseases, and there were 20 patients with improved clinical outcome and 20 patients with death. The isolated strains primarily originated from mid-stream urine and bronchoalveolar lavage fluid. Whole-genome sequencing results revealed that the strains predominantly carried bla KPC-1 (29 strains, 72.5%) and bla NDM-1 (6 strains, 15.0%), with 5 strains carrying both bla KPC-1 and bla NDM-1 . Various virulence genes were detected, among which the carriage rates of genes such as entA , entB , entE , entS , fepA , fepC , fepG , yag / ecp , and ompA reached 100%, while the carriage rates of genes such as entD , fimB , iroB , iroD , fes ,and pla were low. The CRKP strains isolated from ICU were predominantly ST11 (27 cases, 67.5%), with KL64 being the main capsular serotype (29 cases, 72.5%). A total of 23 ST11-KL64 CRKP strains were detected, accounting for 57.5%., Conclusions: The main type of ICU CRKP is ST11-KL64, carrying various virulence genes, primarily those related to iron absorption. Furthermore, bla KPC has shifted from bla KPC-2 to bla KPC-1 . Therefore, close monitoring of the molecular epidemiological changes of CRKP is necessary, and strict control measures should be implemented to effectively curb the occurrence of CRKP infections.

Objective: To investigate the effects of intrauterine perfusion with granulocyte colony-stimulating factor (G-CSF) on the endometrial thickness, volume, and blood flow parameters of patients with thin endometrium and their clinical outcomes., Methods: We designed a prospective non-randomized synchronous controlled trial and recruited patients with thin endometrium who underwent frozen-thawed embryo transfer (FET) at Mianyang Central Hospital between September 1, 2021 and September 1, 2023. They were divided into two groups, an experimental group of patients who received the experimental treatment of intrauterine perfusion with G-CSF and a control group of patients who did not receive the experimental treatment. The general data and the clinical outcomes of the two groups were analyzed and compared. The endometrial thickness, volume and blood flow parameters of patients in the experimental group before and after intrauterine perfusion with G-CSF were analyzed., Results: The clinical data of 83 patients were included in the study. The experimental group included 51 cases, while the control group included 31 cases. There were no significant differences in the baseline data between the two groups. The clinical pregnancy rate of the experimental group (56.86%) was higher than that of the control group (50.00%) and the rate of spontaneous abortion in the experimental group (27.59%) was lower than that in the control group (37.50%), but the differences were not statistically significant ( P >0.05). In the experimental group, the postperfusion endometrial thickness ([0.67±0.1] cm) was greater than the preperfusion endometrial thickness ([0.59±0.09] cm), the postperfusion ([1.84±0.81] cm 3 ) was greater than the preperfusion endometrial volume ([1.54±0.69] cm 3 ), and the postperfusion vascularization flow index (VFI) (1.97±2.82) was greater than the preperfusion VFI (0.99±1.04), with all the differences being statistically significant ( P <0.05)., Conclusion: Intrauterine perfusion with G-CSF can enhance the endometrial thickness, volume, and some blood flow parameters in patients with thin endometrium., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

The evolution of critical care medicine is inextricably linked to the development of critical care procedures. These procedures not only facilitate diagnosis and treatment of critically ill patients, but also provide valuable insights into disease pathophysiology. While critical care interventions offer undeniable benefits, the potential for iatrogenic complications necessitates careful consideration. The recent surge in critical care ultrasound (US) utilization is a testament to its unique advantages: non-invasiveness, real-time bedside availability, direct visualization of internal structures, elimination of ionizing radiation exposure, repeatability, and relative ease of learning. Recognizing the need to optimize procedures and minimize complications, critical care utrasound study group of Beijing critical care ultrasound research assocition convened a panel of critical care experts to generate this consensus statement. This document serves as a guide for healthcare providers, aiming to ensure patient safety and best practices in critical care.

Distant cutaneous metastasis of primary lung squamous cell carcinoma is an exceedingly rare event, with scalp metastasis as the initial clinical presentation even rarer. Scalp skin metastases are prone to be misdiagnosed as other scalp disorders, yet their appearance signifies the deterioration and poor prognosis of lung cancer. This case report documents a female patient presenting initially with scalp folliculitis in dermatology, who was subsequently diagnosed with malignant lung tumor through radiological imaging and referred to Department of Thoracic Surgery. Pathological examination of the excised lesion from the scalp revealed distant metastasis of lung cancer. A review of similar cases reported in literature was conducted. This article aims to enhance understanding and awareness of skin metastasis in lung cancer, to emphasize the importance of this condition, and to improve early recognition and precise diagnosis. It is crucial to prevent clinical misdiagnosis and ensure appropriate treatment, finally leading to improve the prognosis of the patients.
.

Objective: To study the effect of arctigenin(ARG) on adriamycin(ADM) resistance of leukemia cell line K562/A02 and the underlying mechanism., Methods: Human leukemia cell line K562 and ADM-resistant cell line K562/A02 were cultured and treated with 2.5-50 µmol/L ADM. Cell proliferation was measured using CCK-8 method, and half maximal inhibitory concentration (IC 50 ) was calculated. K562/A02 cells were treated with different concentrations of ARG (1, 2, 4, 8, 16 mmol/L) to detect the effect of ARG on K562/A02 cells, and a suitable concentration (2 mmol/L) was selected for subsequent experiments. K562/A02 cells were treated with 2 mmol/L ARG and 5 µmol/L ADM, and cell apoptosis was detected by flow cytometry, the expression of P-gp, MRP, cleaved caspase-3, Bax, Bcl-2 proteins and the TLR4/NF-κB signaling pathway-related proteins were measured by Western blot. TLR4 overexpression plasmid was transfected into K562/A02 cells which were co-treated with ARG and ADM, then drug sensitivity and cell apoptosis were measured., Results: The IC 50 value of ADM on K562/A02 cells was 36.57 µmol/L, which was significantly higher than that on K562 cells (1.30 µmol/L). ARG with a concentration of ≤2 mmol/L did not have a significant effect on K562/A02 cells. 2 mmol/L ARG significantly reduced the IC 50 of ADM on K562/A02 cells. In 5 µmol/L ADM-treated K562/A02 cells, compared with the control group, the apoptosis rate of K562/A02 cells in the ARG group was significantly increased, the expressions of cleaved caspase-3, Bax proteins were significantly upregulated, the expressions of P-gp, MRP, Bcl-2, TLR4, MyD88, and p-NF-κB proteins were significantly downregulated, and the differences were statistically significant ( P < 0.05). After transfection with TLR4 overexpression plasmid, the sensitivity of ARG-treated K562/A02 cells to ADM was reduced ( P < 0.05), the cell apoptosis was decreased, and the expressions of P-gp, MRP, Bcl-2 and TLR4/NF-κB signaling pathway-related proteins were significantly elevated, while the expressions of cleaved caspase-3 and Bax proteins were significantly decreased (all P < 0.05)., Conclusion: ARG may reverse the resistance of human leukemia cell line K562/A02 to ADM by inhibiting TLR4/NF-κB signaling pathway.

Ion chromatography (IC) is a novel high performance liquid chromatographic technique that is suitable for the separation and analysis of ionic substances in different matrix samples. Since 1975, it has been widely used in many fields, such as the environment, energy, food, and medicine. IC compensates for the separation limitations of traditional gas chromatography and high performance liquid chromatography and can realize the qualitative analysis and quantitative detection of strongly polar components. This chromatographic technique features not only simple operations but also rapid analysis. The sensors used in IC are characterized by high sensitivity and selectivity, and the technique can simultaneously separate and determine multiple components. Several advances in IC instrumentation and chromatographic theories have been developed in recent years. IC can analyze various types of samples, including ions, sugars, amino acids, and organic acids (bases). Chinese herbal medicines are typically characterized by highly complex chemical compositions and may contain carbohydrates, proteins, alkaloids, and other active components. They also contain toxic residues such as sulfur dioxide, which may be produced during the processing of medicinal materials. Therefore, the analysis and elucidation of the precise chemical constituents of Chinese herbal medicines present key problems that must be resolved in modern Chinese herbal medicine research. In this context, IC has become an important method for analyzing and identifying the complex components of Chinese herbal medicines because this method is suitable for detecting a single active ingredients among complex components. This paper introduces the different types and principles of IC as well as research progress in this technique. As the applications of IC-based methods in pharmaceutical science, cell biology, and microbiology increase, further development is necessary to expand the applications of this technique. The development of innovative techniques has enabled IC technologies to achieve higher analytical sensitivity, better selectivity, and wider application. The components of Chinese herbal medicines can be divided into endogenous and exogenous components according to their source: endogenous components include glycosides, amino acids, and organic acids, while exogenous components include toxic residues such as sulfur dioxide. Next, the applications of IC to the complex components of Chinese herbal medicines in recent decades are summarized. The most commonly used IC technologies and methods include ion exchange chromatography and conductivity detection. The advantages of IC for the analysis of alkaloids have been demonstrated. This method exhibits better characteristics than traditional analytical methods. However, the applications of IC for the speciation analysis of inorganic anions are limited. Moreover, few reports on the direct application of the technique for the determination of the main active substances in Chinese herbal medicines, including flavonoids, phenylpropanoids, and steroids, have been reported. Finally, this paper reviews new IC technologies and their application progress in Chinese herbal medicine, focusing on their prospects for the effective separation and analysis of complex components. In particular, we discuss the available sample (on-line) pretreatment technologies and explore possible technologies for the selective and efficient enrichment and separation of different components. Next, we assess innovative research on solid-phase materials that can improve the separation effect and analytical sensitivity of IC. We also describe the features of multidimensional chromatography, which combines the advantages of various chromatographic techniques. This review provides a theoretical reference for the further development of IC technology for the analysis of the complex chemical components of Chinese herbal medicines.

Objective: To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+0., Methods: A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple., Results: The female partner was identified as a carrier of the rare SMN1[2+0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion., Conclusion: PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

Objective: To investigate the risk factors for delayed union of extra-articular fractures of the middle and lower third of the tibia treated by locking plate., Methods: Total of 135 patients of extra-articular fractures of the middle and lower third of the tibia from January 2013 to December 2018 were retrospectively analyzed, including 85 males and 50 females, ranged from 19 to 80 years old. All cases were treated with locking plates. The patients were divided into union group and delayed union group according to the condition of fracture union. The risk factors of delayed healing were determined by univariate analysis of 14 factors that might affect fracture healing first, then the factors with significance were analyzed by binary Logistic regression., Results: There were 13 patients of delayed union, and the rate of delayed union was 9.63%. Univariate analysis showed that delayed union was associated with age, smoking, reduction method, anemia and time of preoperative preparation. Regression analysis showed that age[ OR =0.849, 95% CI （0.755, 0.954）, P =0.006], smoking[ OR =0.020, 95% CI （0.002, 0.193）, P =0.001], reduction method[ OR =23.924, 95% CI （2.210, 258.943）, P =0.009], anemia[ OR =0.016, 95% CI （0.001, 0.289）, P =0.005] were the contributory factors for delayed union., Conclusion: Young age, smoking, closed reduction and anemia are the risk factors for delayed union of extra-articular fractures of the middle and lower third of the tibia treated by locking plate.

Objective: To evaluate the effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source in Sichuan Province from 2010 to 2022, so as to provide insights into formulation of future control interventions., Methods: Data pertaining to comprehensive echinococcosis control measures with emphasis on management of infectious source and echinococcosis surveillance in Sichuan Province from 2010 to 2022 were collected. The effectiveness of comprehensive echinococcosis control measures with emphasis on management of infectious source was evaluated with prevalence of human echinococcosis, detection of newly diagnosed echinococcosis patients, prevalence of Echinococcus infection in domestic dogs, prevalence of cystic echinococcosis in livestock, prevalence of alveolar echinococcosis in small mammals and awareness of echinococcosis control knowledge, and Spearman's rank correlation analysis., Results: The prevalence of human echinococcosis reduced from 1.08% in 2010 to 0.40% in 2022 in Sichuan Province (χ 2 = 1 482.97, P < 0.05), with a reduction from 0.30% to 0.02% in the detection of newly diagnosed echinococcosis cases (χ 2 = 2 776.41, P < 0.05), a reduction from 15.87% to 0.46% in the prevalence of Echinococcus infection in domestic dogs (χ 2 = 20 823.96, P < 0.05), a reduction from 8.05% to 1.07% in the prevalence of cystic echinococcosis in livestock (χ 2 = 1 296.02, P < 0.05), and the awareness of echinococcosis control knowledge increased from 50.65% to 95.24% (χ 2 = 34 938.63, P < 0.05); in addition, there was a year-specific prevalence rate of alveolar echinococcosis in small mammals (χ 2 = 164.07, P < 0.05). Spearman's rank correlation analysis revealed that the detection of newly diagnosed echinococcosis cases correlated positively with the prevalence of Echinococcus infections in domestic dogs ( r s = 0.823, P < 0.05) and the prevalence of cystic echinococcosis in livestock ( r s = 0.795, P < 0.05), and correlated negatively with the awareness of echinococcosis control knowledge ( r s = - 0.918, P < 0.05), and the prevalence of Echinococcus infection in domestic dogs correlated positively with the prevalence of cystic echinococcosis in livestock ( r s = 0.753, P < 0.05) and negatively with the awareness of echinococcosis control knowledge ( r s = -0.747, P < 0.05); however, there was no correlation between the prevalence of Echinococcus infections in domestic dogs and the prevalence of alveolar echinococcosis in small mammals ( r s = -0.750, P > 0.05)., Conclusions: The comprehensive echinococcosis control measures with emphasis on management of infectious source had achieved remarkable effectiveness in Sichuan Province; however, the transmission chain of echinococcosis has not been interrupted. Reinforced comprehensive echinococcosis control measures with emphasis on management of infectious source and sustained tracking evaluation of the effectiveness are recommended in Sichuan Province.

Objective: To investigate the prevalence and epidemiological characteristics of taeniasis and cysticercosis among residents in Tibetan agricultural areas of Sichuan Province, so as to provide insights for the prevention and control of taeniasis and cysticercosis., Methods: From 2016 to 2022, Kangding City, Daocheng County, Derong County, Ruoergai County and Muli Tibetan Autonomous County were sampled from Tibetan agricultural areas of Ganzi Tibetan Autonomous Prefecture, Aba Tibetan and Qiang Autonomous Prefecture and Liangshan Yi Autonomous Prefecture in Sichuan Province, and 1 to 6 townships were sampled from each county (district), followed by 4 to 7 villages sampled from each township. Primary school children were sampled using a cluster sampling method, and permanent residents at ages of over 16 years were randomly sampled from each village. Participants' demographics, history of tapeworm excretion during the past year and clinical symptoms and signs of cysticercosis were collected through questionnaire surveys, and participants' stool and venous blood samples were collected. Taenia eggs were detected in stool samples using the direct smear method, and deworming was performed among taeniasis patients with areca nut-squash seeds. The tapeworm species were identified using a multiplex PCR assay, and serum specific IgG antibody against cysticercus was detected using enzyme-linked immunosorbent assay (ELISA)., Results: A total of 5 249 respondents participated in the questionnaire survey, including 603 respondents (11.5%) with a self-reported history of proglottids secretion during the past year. A total of 3 976 residents were subjected to stool examinations, and the detection of Taenia eggs was 6.5%. Of 258 participants undergoing deworming, there were 403 cases (94.2%) with excretions of Taenia worms or proglottids. The mean prevalence of taeniasis was 10.9% (439/4 043), and there were gender-, age- and region-specific prevalence rates of taeniasis (χ 2 = 36.73, 126.31 and 163.41, all P values < 0.05). Multiplex PCR assays detected 41 cases with T. solium infections (12.5%), 197 cases with T. saginata infections (59.9%) and 91 cases with T. asiatica infections (27.6%) among 329 patients undergoing deworming, and there were region-specific prevalence rates of T. solium , T. saginata and T. asiatica infections (χ 2 = 45.39, P < 0.05). In addition, the sero-prevalence of anti-cysticercus IgG antibody was 7.0% (345/4 933), and there were age- and region-specific sero-prevalence rates of anti-cysticercus IgG antibody (χ 2 = 13.49 and 51.76, both P values < 0.05)., Conclusions: Multiple Taenia species are prevalent in Tibetan agricultural areas of Sichuan Province and the sero-prevalence of anti-cysticercus antibody is high among residents. Monitoring and control of taeniasis and cysticercosis should be strengthened.

Objective: To establish a machine learning radiomics model that can accurately predict MRI enhancement patterns of glioma based on T2 fluid attenuated inversion recovery (T2-FLAIR) images for optimizing the workflow of magnetic resonance imaging (MRI) examinations of glioma patients., Methods: We retrospectively collected preoperative MR T2-FLAIR images from 385 patients with pathologically confirmed glioma, who were divided into enhancing and non-enhancing groups according to the enhancement pattern. Predictive radiomics models were established using Gaussian Process, Linear Regression, Linear Regression-Least absolute shrinkage and selection operator, Support Vector Machine, Linear Discriminant Analysis or Naive Bayes as the classifiers in the training cohort ( n =201)and tested both in the internal ( n =85) and external validation cohorts ( n =99). The receiver-operating characteristic curve was used to assess the predictive performance of the models., Results: The predictive model constructed based on 15 radiomics features using Gaussian Process as the classifier had the best predictive performance in both the training cohort and the internal validation cohort, with areas under the curve (AUC) of 0.88 (95% CI : 0.81-0.94) and 0.80 (95% CI : 0.71-0.88), respectively. In the external validation cohort, the model showed an AUC of 0.81 (95% CI : 0.71-0.90) with sensitivity, specificity, positive predictive value and negative predictive value of 0.98, 0.61, 0.76 and 0.96, respectively., Conclusion: The T2-FLAIR-based machine learning radiomics model can accurately predict the enhancement pattern of gliomas on MRI.

Background: Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1)., Methods: The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group., Results: Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05)., Conclusions: FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.

Objective: To review the research progress of rapid surgery for hip fracture in elderly patients., Methods: The published studies, expert consensus, and guidelines at home and abroad were systematically summarized from the aspects of the characteristics of aging population, the benefits of rapid surgery, the disadvantages of delayed surgery, and the recommendations of current guidelines, so as to further guide clinical practice., Results: Hip fracture is a common fracture type in the elderly population. As elderly patients generally have poor physique and often have a variety of underlying diseases, such as hypostatic pneumonia, bedsore, lower limb vein thrombosis, and other complications in conservative treatment, its disability rate and mortality are high, so surgical treatment is the first choice. At present, most relevant studies and expert consensus and guidelines at home and abroad support rapid surgery, that is, preoperative examination should be started immediately after admission, and adverse factors such as taking anticoagulant drugs, serious cardiovascular diseases, and severe anemia should be clearly and actively corrected, and surgery should be completed within 48 hours after admission as far as possible. Rapid surgery can not only significantly reduce the mortality of patients, but also reduce the length of hospital stay and the incidence of perioperative cognitive impairment, which is conducive to the recovery of patients with pain during hospitalization and postoperative function, and improve the prognosis of patients., Conclusion: In order to avoid many problems caused by delayed surgery, the elderly patients with hip fracture should be operated as soon as possible under the condition of actively correcting the adverse factors. Comprehensive evaluation and preparation, the development of an individualized surgical plan, and the formation of a multidisciplinary medical team can reduce surgical risks and improve effectiveness.

Objective: To investigate the effect of the trace element zinc (Zn) on apoptosis and cell proliferation in palate shelvesduring the fusion phase, and to screen candidate genes of the Zn-finger special protein (Sp) family that were differentially expressed between the cleft palate and the normal palate to explore the mechanism of Zn in the development of cleft palate. Methods: Zn-rich, normal-Zn, low-Zn, and Zn-deficient diets were fed to female mice and, for the resultant fetuses, paraffin slices of their heads were made at embryonicdays 14.5 and 16.5. Using terminaldeoxynucleotidyltransferase-mediated dUTP nick-end labeling, the number of apoptotic cells in the palatal shelves was counted, and cell proliferation activity was detected using proliferating cell nuclear antigen staining. Total RNA from the palatal shelves of fetal mice was extracted from the Zn-rich diet, normal Zn-diet, and Zn-deficient-diet groups. We used microarray analysis to examine the expression of genes to identify intergroup differential gene expression and polymerase chain reaction tests to validate the results. Results: At ED14.5, the incidence of cleft palate in the regular zinc group, zinc rich group, low zinc group, and zinc deficient group was 8% (3/36), 2% (1/39), 29% (12/41), and 39% (15/38), respectively. The HE staining results at ED14.5 showed that both the left and right palatal processes in the zinc group had been lifted up and were in contact and connected with each other. In the zinc deficiency group, the left and right palatine processes remained vertically downwards on both sides of the tongue, ultimately forming cleft palate; In the low zinc group, the left and right palatine processes were raised but not in contact, ultimately resulting in cleft palate. There is no significant difference between the zinc rich group and the regular zinc group. At ED14.5, the positive rates of proliferative cells in the palatal process of fetal mice in the regular zinc group (80.29% ± 7.39%) and the zinc rich group (87.69% ± 6.62%) were significantly higher than those in the zinc deficient group (56.05% ± 16.13%) and the low zinc group (56.22% ± 9.61%) ( t =4.32, P <0.05). The apoptosis index of fetal rat palatal process cells in the zinc deficient group (38.80% ± 3.10%) and the low zinc group (28.80% ± 6.19%) were significantly higher than those in the regular zinc group (16.80% ± 1.82%) ( t =19.35, P <0.001; t =5.81, P <0.001). There were 663 differentially expressed genes in the zinc rich group and the zinc deficient group, with 513 up-regulated genes and 150 down-regulated genes, among which Sp5 was found to be located. The real time PCR results showed that compared with the regular zinc group (2.22 ± 0.36), the expression level of Sp5mRNA in the palatal process tissue of the zinc deficient group (1.23 ± 0.38) significantly increased ( P <0.05), while the zinc rich group (3.68 ± 0.90) significantly decreased ( P <0.05). Conclusions: Trace element Zn content was found to be closely related to the occurrence of cleft palate in mice offspring, with a lack of Zn leading to cleft palate.

Acute respiratory and circulatory disorders are the most common critical syndromes, the essence of which is damage to the organs/systems of the heart and lungs. These comprise the essential manifestation of disease and injury progression to the severe stage. Its development involves the following components: individual specificity, primary disease strike, dysregulation of the host's response, and systemic disorders. Admission for acute respiratory and circulatory disorders is a clinical challenge. Based on a previously proposed flow, a critical care ultrasound-based stepwise approach (PIEPEAR) as a standard procedure to manage patients with acute cardiorespiratory compromise and practical experience in recent years, a modified seven-step analysis and treatment process has been developed to help guide clinicians with rational thinking and standardized treatment when faced with acute respiratory and circulatory disorders. The process consists of seven steps: problem-based clinical analysis, intentional information acquisition, evaluation of core disorder based on critical care ultrasound, pathophysiology and host response phenotype identification, etiology diagnosis, act treatment through pathophysiology-host response and etiology, and re-check. The modified seven-step approach is guided by a "modular analysis" style of thinking and visual monitoring. This approach can strengthen the identification of clinical problems and facilitate a three-in-one analysis. It focuses on pathophysiological disorders, body reactions, and primary causes to more accurately understand the condition's key points, and make treatment more straight forward, to finally achieve the aim of "comprehensive cognition and refined treatment".

The portable light-weight magnetic resonance imaging system can be deployed in special occasions such as Intensive Care Unit (ICU) and ambulances, making it possible to implement bedside monitoring imaging systems, mobile stroke units and magnetic resonance platforms in remote areas. Compared with medium and high field imaging systems, ultra-low-field magnetic resonance imaging equipment utilizes light-weight permanent magnets, which are compact and easy to move. However, the image quality is highly susceptible to external electromagnetic interference without a shielded room and there are still many key technical problems in hardware design to be solved. In this paper, the system hardware design and environmental electromagnetic interference elimination algorithm were studied. Consequently, some research results were obtained and a prototype of portable shielding-free 50 mT magnetic resonance imaging system was built. The light-weight magnet and its uniformity, coil system and noise elimination algorithm and human brain imaging were verified. Finally, high-quality images of the healthy human brain were obtained. The results of this study would provide reference for the development and application of ultra-low-field magnetic resonance imaging technology.

Chronic cough is a common complaint in respiratory specialist clinics, with a significant impact on cough-specific quality of life and psychophysiological health. The diagnosis, treatment and management of chronic cough remains a major challenge. We summarized a series of recent advances from clinical studies in the epidemiology, diagnosis and management of chronic cough over the past year.

Objective: To evaluate the therapeutic efficacy of lifetide biofeedback intervention in patients with type 2 diabetes mellitus (T2DM)., Methods: We analyzed the changes in average blood glucose, estimated glycosylated hemoglobin (HbA1c), fasting blood glucose and HbA1c levels in 5 patients with T2DM undergoing lifetide biofeedback intervention without the use of hypoglycemic drugs. A transient blood glucose monitoring system was used for drug withdrawal management during the intervention., Results: Compared with those before the intervention, the average blood glucose and fasting blood glucose and HbA1c levels showed no significant changes after the intervention without using hypoglycemic drugs ( P >0.05), but the estimated HbA1c was significantly decreased after the intervention ( P <0.05). Two patients achieved complete remission, two showed partial remission, and one had substantially improved blood glucose levels. One patient showed a marked increase in extremity temperature after the intervention ( P <0.05). Another patient had a significantly increased heart rate variability index ( P <0.05) without obvious changes in heart rate after the intervention ( P >0.05)., Conclusion: By reestablishing the balance in autonomic nervous system regulation and enhancing peripheral microcirculation, lifetide biofeedback intervention helps to maintain stable blood glucose levels, achieve disease remission, and reduce the occurrence of complications in T2DM patients after discontinuation of hypoglycemic drugs without changing their lifestyles.

Objective: To determine the changes in the expression of circular RNA Circ-PALLD in heart failure and explore the biogenesis of Circ-PALLD., Methods: We analyzed second-generation sequencing results of human and murine heart failure samples to identify the candidate CircRNAs. Sanger generation sequencing was performed after PCR amplification, and the sequencing results were compared to determine the reverse splicing pattern of the corresponding CircRNAs. We further examined the expressions of CircRNAs and linear RNAs in 8 patients with heart failure admitted in our hospital, and RT-qPCR was performed to detect the expression levels of Circ-PALLD and PALLD in the failing myocardium. Bioinformatic analysis was performed to predict the transcription factors that may regulate PALLD. Small interfering RNAs (siRNAs) against GATA4 were used to determine the regulatory effect of the transcription factor GATA4 on PALLD., Results: Sanger sequencing and sequence alignment verified the reverse splicing of Circ-VWA8, Circ-VMP1, Circ-PRDM5, Circ-PLCL2, Circ-PALLD, Circ-NFATC3, Circ-MLIP, Circ-FAM208A, Circ-ANKIB1, and Circ-AGTPBP1, demonstrated their loop-forming nature and determined the exon arrangement of reverse splicing. Semi-quantitative PCR results showed that the expression levels of CircPALLD, Circ-NFATC3 and Circ-AGTPBP1 were significantly increased while the expression level of linear PALLD was significantly decreased in the myocardial tissues of heart failure patients. Bioinformatic analysis suggested that the transcription of PALLD was regulated possibly by the transcription factor GATA4. RT-qPCR showed that the expression level of Circ-PALLD was significantly increased, while PALLD expression was significantly decreased in the failing myocardium, which was consistent with the results of semi-quantitative PCR. In primary mammary rat cardiomyocytes, GATA4 knockdown resulted in lowered expressions of both Circ-PALLD and PALLD., Conclusion: Circ-PALLD is highly expressed in heart failure and can be used as a novel molecular marker for chronic heart failure, and GATA4 may play important role in regulating its transcription. Circ-PALLD points a new direction for investigating the molecular mechanism of heart failure and may also serve as a potential therapeutic target for heart failure.

Objective: To establish the finite element model of varus-type ankle arthritis and to implement the finite element mechanical analysis of different correction models for tibial anterior surface angle (TAS) in supramalleolar osteotomy., Methods: A female patient with left varus-type ankle arthritis (Takakura stage Ⅱ, TAS 78°) was taken as the study object. Based on the CT data, the three-dimensional model of varus-type ankle arthritis (TAS 78°) and different TAS correction models [normal (TAS 89°), 5° valgus (TAS 94°), and 10° valgus (TAS 99°)] were created by software Mimics 21.0, Geomagic Wrap 2021, Solidworks 2017, and Workbench 17.0. The 290 N vertical downward force was applied to the upper surface of the tibia and 60 N vertical downward force to the upper surface of the fibula. Von Mises stress distribution and stress peak were calculated., Results: The finite element model of normal TAS was basically consistent with biomechanics of the foot. According to biomechanical analysis, the maximum stress of the varus model appeared in the medial tibiotalar joint surface and the medial part of the top tibiotalar joint surface. The stress distribution of talofibular joint surface and the lateral part of the top tibiotalar joint surface were uniform. In the normal model, the stress distributions of the talofibular joint surface and the tibiotalar joint surface were uniform, and no obvious stress concentration was observed. The maximum stress in the 5° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress distribution of medial tibiotalar joint surface was uniform. The maximum stress of the 10° valgus model appeared at the posterior part of the talofibular joint surface and the lateral part of the top tibiotalar joint surface. The stress on the medial tibiotalar joint surface increased., Conclusion: With the increase of valgus, the stress of ankle joint gradually shift outwards, and the stress concentration tends to appear. There was no obvious obstruction of fibula with 10° TAS correction. However, when TAS correction exceeds 10° and continues to increase, the obstruction effect of fibula becomes increasingly significant.

Objective: To investigate the risk factors for pulmonary atelectasis in adults with tracheobronchial tuberculosis(TBTB). Methods: Clinical data of adult patients (≥18 years old) with TBTB from February 2018 to December 2021 in Public Health Clinical Center of Chengdu were retrospectively analyzed. A total of 258 patients were included, with a male to female ratio of 1∶1.43. The median age was 31(24, 48) years. Clinical data including clinical characteristics, previous misdiagnoses/missed diagnoses before admission, pulmonary atelectasis, the time from symptom onset to atelectasis and bronchoscopy, bronchoscopy and interventional treatment were collected according to the inclusion and exclusion criteria. Patients were divided into two groups according to whether they had pulmonary atelectasis. Differences between the two groups were compared. Binary logistic regression was used to analyze the risk factors for pulmonary atelectasis. Results: The prevalence of pulmonary atelectasis was 14.7%, which was most common in the left upper lobe (26.3%). The median time from symptom onset to atelectasis was 130.50(29.75,358.50)d, and the median time from atelectasis to bronchoscopy was 5(3,7)d. The median age, the proportion of misdiagnosis of TBTB before admission, and the time from symptom onset to bronchoscopy in the atelectasis group were higher than those without atelectasis, and the proportion of receiving bronchoscopy examination and interventional therapy previously, and the proportion of pulmonary cavities were lower than those without atelectasis (all P <0.05). The proportions of cicatrices stricture type and lumen occlusion type in the atelectasis group were higher than those without atelectasis, while the proportions of inflammatory infiltration type and ulceration necrosis type were lower than those without atelectasis (all P <0.05). Older age ( OR =1.036, 95% CI : 1.012-1.061), previous misdiagnosis( OR =2.759, 95% CI : 1.100-6.922), longer time from symptom onset to bronchoscopy examination ( OR =1.002, 95% CI : 1.000-1.005) and cicatrices stricture type ( OR =2.989, 95% CI : 1.279-6.985) were independent risk factors for pulmonary atelectasis in adults with TBTB (all P <0.05). Of the patients with atelectasis who underwent bronchoscopy interventional therapy, 86.7% had lung reexpansion or partial reexpansion. Conclusions: The prevalence of pulmonary atelectasis is 14.7% in adult patients with TBTB. The most common site of atelectasis is left upper lobe. The TBTB type of lumen occlusion is complicated by pulmonary atelectasis in 100% of cases. Being older, misdiagnosed as other diseases, longer time from onset of symptoms to bronchoscopy examination, and being the cicatrices stricture type are factors for developing pulmonary atelectasis. Early diagnosis and treatment are needed to reduce the incidence of pulmonary atelectasis and increase the rate of pulmonary reexpansion.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.

Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 μg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.

Objective: To analyze the femoral head collapse and the operation of osteonecrosis of the femoral head (ONFH) in different Japanese Investigation Commitee (JIC) types, in order to summarize the prognostic rules of each type of ONFH, and explore the clinical significance of CT lateral subtypes based on reconstruction of necrotic area of C1 type and verify their clinical effect., Methods: A total of 119 patients (155 hips) with ONFH between May 2004 and December 2016 were enrolled in the study. The total hips consisted of 34 hips in type A, 33 in type B, 57 in type C1, and 31 in type C2, respectively. There was no significant difference in age, gender, affected side, or type of ONFH of the patients with differenct JIC types ( P >0.05). The 1-, 2-, and 5-year femoral head collapse and operation of different JIC types were analyzed, as well as the survival rate (with femoral head collapse as the end point) of hip joint between different JIC types, hormonal/non-hormonal ONFH, asymptomatic and symptomatic (pain duration >6 months or ≤6 months), and combined preserved angle (CPA) ≥118.725° and CPA<118.725°. JIC types with significant differences in subgroup surgery and collapse and with research value were selected. According to the location of the necrotic area on the surface of the femoral head, the JIC classification was divided into 5 subtypes in the lateral CT reconstruction, and the contour line of the necrotic area was extracted and matched to the standard femoral head model, and the necrosis of the five subtypes was presented by thermography. The 1-, 2-, and 5-year outcomes of femoral head collapse and operation in different lateral subtypes were analyzed, and the survival rates (with collapse of the femoral head as the end point) between CPA≥118.725° and CPA<118.725° hip in patients with this subtype were compared, as well as the survival rates of different lateral subtypes (with collapse and surgery as the end points, respectively)., Results: The femoral head collapse rate and operation rate in the 1-, 2-, and 5-year were significantly higher in patients with JIC C2 type than in patients with other hip types ( P <0.05), while in patients with JIC C1 type than in patients with JIC types A and B ( P <0.05). The survival rate of patients with different JIC types was significantly different ( P <0.05), and the survival rate of patients with JIC types A, B, C1, and C2 decreased gradually. The survival rate of asymptomatic hip was significantly higher than that of symptomatic hip, and the survival rate of CPA≥118.725° was significantly higher than that of CPA<118.725° ( P <0.05). The lateral CT reconstruction of type C1 hip necrosis area was selected for further classification, including type 1 in 12 hips, type 2 in 20 hips, type 3 in 9 hips, type 4 in 9 hips, and type 5 in 7 hips. There were significant differences in the femoral head collapse rate and the operation rate among the subtypes after 5 years of follow-up ( P <0.05). The collapse rate and operation rate of types 4 and 5 were 0; the collapse rate and operation rate of type 3 were the highest; the collapse rate of type 2 was high, but the operation rate was lower than that of type 3; the collapse rate of type 1 was high, but the operation rate was 0. In JIC type C1 patients, the survival rate of the hip joint with CPA≥118.725° was significantly higher than that with CPA<118.725° ( P <0.05). In the follow-up with femoral head collapse as the end point, the survival rates of types 4 and 5 were all 100%, while the survival rates of types 1, 2, and 3 were all 0, and the difference was significant ( P <0.05). The survival rate of types 1, 4, and 5 was 100%, of type 3 was 0, and of type 2 was 60%, showing significant difference ( P <0.05)., Conclusion: JIC types A and B can be treated by non-surgical treatment, while type C2 can be treated by surgical treatment with hip preservation. Type C1 was classified into 5 subtypes by CT lateral classification, type 3 has the highest risk of femoral head collapse, types 4 and 5 have low risk of femoral head collapse and operation, type 1 has high femoral head collapse rate but low risk of operation; type 2 has high collapse rate, but the operation rate is close to the average of JIC type C1, which still needs to be further studied.

Objective: To determine whether the adenine base editor (ABE7.10) can be used to fix harmful mutations in the human G6PC3 gene. Methods: To investigate the safety of base-edited embryos, off-target analysis by deep sequencing was used to examine the feasibility and editing efficiency of various sgRNA expression vectors. The human HEK293T mutation models and human embryos were also used to test the feasibility and editing efficiency of correction. Results: ①The G6PC3(C295T) mutant cell model was successfully created. ②In the G6PC3(C295T) mutant cell model, three distinct Re-sgRNAs were created and corrected, with base correction efficiency ranging from 8.79% to 19.56% . ③ ABE7.10 could successfully fix mutant bases in the human pathogenic embryo test; however, base editing events had also happened in other locations. ④ With the exception of one noncoding site, which had a high safety rate, deep sequencing analysis revealed that the detection of 32 probable off-target sites was <0.5% . Conclusion: This study proposes a new base correction strategy based on human pathogenic embryos; however, it also produces a certain nontarget site editing, which needs to be further analyzed on the PAM site or editor window.

Objective: To explore the genetic basis for 7 families with gonadal mosaicism for Duchenne muscular dystrophy (DMD)., Methods: For the 7 families presented at the CITIC Xiangya Reproductive and Genetic Hospital from September 2014 to March 2022, clinical data were collected. Preimplantation genetic testing for monogenic disorders (PGT-M) was carried out for the mother of the proband from family 6. Peripheral venous blood samples of the probands, their mothers and other patients from the families, amniotic fluid samples from families 1 ~ 4 and biopsied cells of embryos cultured in vitro from family 6 were collected for the extraction of genomic DNA. Multiplex ligation-dependent probe amplification (MLPA) was carried out for the DMD gene, and short tandem repeat (STR)/single nucleotide polymorphism (SNP)-based haplotypes were constructed for the probands, other patients, fetuses and embryos., Results: The results of MLPA showed that the probands and the fetuses/probands' brothers in families 1 ~ 4, 5, 7 had carried the same DMD gene variants, whilst the probands' mothers were all normal. The proband in family 6 carried the same DMD gene variant with only 1 embryo (9 in total) cultured in vitro, and the DMD gene of the proband's mother and the fetus obtained through the PGT-M were normal. STR-based haplotype analysis showed that the probands and the fetuses/probands' brothers in families 1 ~ 3 and 5 have inherited the same maternal X chromosome. SNP-based haplotype analysis showed that the proband from family 6 has inherited the same maternal X chromosome with only 1 embryo (9 in total) cultured in vitro. The fetuses in families 1 and 6 (via PGT-M) were both confirmed to be healthy by follow up, whilst the mothers from families 2 and 3 had chosen induced labor., Conclusion: Haplotype analysis based on STR/SNP is an effective method for judging gonad mosaicism. Gonad mosaicisms should be suspected for women who have given births to children with DMD gene variants but with a normal peripheral blood genotype. Prenatal diagnosis and reproductive intervention may be adapted to reduce the births of further affected children in such families.

Global warming and regional extreme climates will lead to unbalanced rainfall, melting glaciers, and permafrost degradation in alpine and arid mountain plains, thereby changing the regional hydrological cycle. The relationship between surface water and groundwater conversion is one of the important scientific issues of hydrological cycle climate response in alpine arid areas. Taking the Datong River Basin at the southern foot of the Qilian Mountains as the study area, based on 119 sets of basic hydrochemical parameters and deuterium-oxygen isotope data, using multivariate statistical analysis and isotopic techniques, the hydrochemical characteristics of surface water and groundwater in the basin and their mutual transformation process were studied. The results showed that the surface water was HCO 3 -Mg·Ca type, which was mainly controlled by rock weathering, whereas the groundwater was HCO 3 -Mg·Ca type and Cl·SO 4 -Na type, which was controlled by rock weathering and evaporation concentration. There was a small amount of calcium and magnesium feldspar dissolved in the upstream groundwater, and the chemical components of the midstream groundwater were mainly the weathering and dissolution of carbonate rocks. The contribution rates of weathering filtration, anthropogenic activities, native sedimentary environment, alternating adsorption of cations, and other factors to the chemical components of surface water and groundwater in the study area were 39.1%, 15.0%, 12.6%, 13.8%, and 19.5%, respectively. The deuterium and oxygen isotope contents of Datong River water showed a trend of enrichment to depletion along the groundwater flow direction. The δ D and δ 18 O isotope test results showed that the deuterium and oxygen isotope content in the Datong River along the groundwater flow showed a trend of enrichment to depletion. The upper and middle reaches of the Datong River were mainly recharged by atmospheric precipitation, whereas the lower reaches were affected by geological structure and influenced by hydrogeological conditions, which was mainly due to diving and spring water overflow to supply river water, as the discharge area of groundwater.

Objective: To investigate the prevalence of Echinococcus infection in small mammals in Shiqu County, Sichuan Province from 2015 to 2020, so as to provide insights into echinococcosis control in Shiqu County., Methods: One setting with frequent activity of small mammals was sampled as the survey site from each of 9 townships where human alveolar echinococcosis was hyperendemic, in Shiqu County, Sichuan Province from 2015 to 2020. Two quadrats measuring 50 m × 50 m were assigned in each survey site during the period between July and August from 2015 to 2020 to capture all small mammals in quadrats, and the species of small mammals were identified by morphological characteristics. All captured small mammals were dissected in the field and Echinococcus infection was identified by visual examinations. The affected organs of Echinococcus - infected small mammals were collected, and Echinococcus infection was detected using PCR assay, with Echinococcus species characterized. The prevalence of Echinococcus infection was calculated in small mammals, and the trends in the prevalence of Echinococcus infection were analyzed during the period from 2015 to 2020. In addition, the prevalence of Echinococcus infection was compared in small mammals using visual examinations and PCR assay., Results: A total of 2 692 small mammals were captured in the survey sites of Shiqu County from 2015 to 2020, and morphology characterized 1 360 Microtus fuscus (50.52%) and 1 332 Plateau pika (49.48%). The prevalence rates of Echinococcus infection were 35.63%, 19.16%, 21.41%, 8.40%, 7.68% and 4.44% by visual examinations and 18.96%, 5.36%, 5.61%, 4.58%, 3.30% and 0.37% by PCR assay in small mammals in Shiqu County from 2015 to 2020, both showing a tendency towards a decline year by year (χ 2 = 215.024 and 117.045, both P values < 0.001). The prevalence of Echinococcus infection was significantly higher in small mammals by visual examinations than by PCR assay during the period from 2015 to 2020 except in 2018 (χ 2 = 33.597, 21.815, 51.373, 17.268 and 9.537, all P values < 0.01). PCR assay detected a reduction in the prevalence of E. multilocularis infection from 10.21% to 0.37% and a reduction in the prevalence of E. shiquicus infection from 8.75% to 0 in small mammals in Shiqu County from 2015 to 2020, both appearing a tendency towards a decline year by year (χ 2 = 117.045 and 43.436, both P values < 0.001). In addition, the prevalence of E. multilocularis and E. shiquicus infections reduced from 15.19% to 0.45% and from 8.23% to 0 in M. fuscus , and the prevalence of E. multilocularis and E. shiquicus infections reduced from 7.76% to 0 and from 9.01% to 0 in P. pika in Shiqu County from 2015 to 2020., Conclusions: M. fuscus and P. pika were dominant species of small mammals in Shiqu County, Sichuan Province from 2015 to 2020, and E. multilocularis infection was mainly found in M. fuscus and E. shiquicus infection mainly found in P. pika . The prevalence of Echinococcus infection appeared a tendency towards a decline in both M. fuscus and P. pika year by year during the period from 2015 to 2020.

Objective: To observe the effect of electroacupuncture (EA) on pain behavior, synovial inflammatory response and demyelination of saphenous nerve in the rats modeled with knee osteoarthritis (KOA) and explore the effect mechanism of EA for reliving allodynia., Methods: Eighty-four male SD rats were randomly divided into a control group, a model group and an EA group, 28 rats in each one. Intra-articular injection of sodium monoiodoacetate (MIA) was administered in right knee joint of each rat in the model group and the EA group to establish the KOA model. In the EA group, separately, on day 5, 7 and 9 after modeling, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) on the right side, with disperse-dense wave (2 Hz/15 Hz), 1 mA in current intensity, for 30 min in one intervention, once a day, and 3 interventions were required. On the 9th day after modeling, the weight-bearing rate was calculated for the affected limbs of the rats in each group, the synovial morphological changes were observed using HE and Masson staining, flow cytometry was adopted to detect the synovial immunocyte counts, and MSD multi-spot assay was used to detected the synovial inflammatory cytokine content. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was observed in each group and the ultrastructure of the saphenous nerve was observed under transmission electron microscopy., Results: On the 9th day after modeling, compared with the control group, the weight-bearing rate of the affected limb was reduced ( P <0.01), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis occurred in the affected limb; the counts of synovial CD11b + cells and M1 macrophages (CD11b + CD86 + ) were increased ( P <0.01), the contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, IL-10 and IL-13 in the synovial tissue were elevated ( P <0.01, P <0.05) for the rats of the model group. Compared with the model group, the weight-bearing rate of the affected limb was increased ( P <0.05), the synovial hyperplasia, inflammatory cell infiltration and synovial fibrosis were mitigated, the counts of CD11b + cells and M1 macrophages (CD11b + CD86 + ) in the synovial tissue, and the contents of TNF-α and IL-6 were reduced ( P <0.01, P <0.05) in the EA group. On the 14th day after modeling, the hind-paw mechanical withdrawal threshold was reduced in the model group when compared with the control group ( P <0.01), and it was increased in the EA group when compared with the model group ( P <0.05). Besides, in the model group, obviously, the myelin sheath structure was destroyed, the myelin layer was disintegrated and loosened, the axon was extruded or the layer thicken and cracked. Compared with the model group, the injury of saphenous nerve was alleviated remarkably in the EA group., Conclusion: The intervention with EA may attenuate the synovial inflammatory response and the injury of saphenous nerve in the affected limb of the rat with KOA, so that the spontaneous pain during the synovial inflammatory response stage and allodynia at the later stage are relieved.

Objective To investigate the effect of connexin 43 (Cx43) on M1 polarization of mouse RAW264.7 macrophages induced by lipopolysaccharide (LPS). Methods RAW264.7 macrophages were cultured in vitro and randomly divided into four groups: control group, LPS group, LPS combined with Gap19 group, LPS combined with Gap26 group. The protein levels of Cx43 and M1 polarization marker CD86 and inducible nitric oxide synthase (iNOS) in mouse RAW264.7 macrophages were detected by Western blot analysis. The expression and localization of CD86 in RAW264.7 macrophages were observed by immunofluorescence cytochemistry, and the expression frequency of M1 polarization marker CD86 in mouse RAW264.7 macrophages was detected by flow cytometry. Results Compared with the control group, the protein expression of CD86, iNOS and Cx43, as well as the expression frequency of CD86 in LPS group showed a significant increase. However, compared with LPS group, the protein expression of CD86 and iNOS, and the expression frequency of CD86 decreased significantly in LPS combined with Gap19 group and LPS combined with Gap26 group. As such, LPS could induce M1 polarization of macrophage, while Gap19 and Gap26 can reduce the expression of M1 polarization markers. Conclusion M1 polarization of macrophages can be inhibited by blocking Cx43.

Objective: To investigate the mechanism of electroacupuncture (EA) "Zusanli" (ST36) in delaying colon "inflammation-cancer transformation" in mice by anti-inflammatory., Methods: C57BL/6J mice were randomly divided into normal, model and EA groups, with 12 mice in each group. The mouse model of colorectal cancer (CRC) was established by intrape-ritoneal injection of azomethane (AOM) and feeding dextran sodium sulfate (DSS). At the beginning of the 2 nd cycle, EA was applied to bilateral ST36 for 30 min once every other day for 12 times. The number of colon tumors in each group was observed, and the weight and length of colon were recorded. The contents of interleukin (IL)-1β, IL-6, IL-17A, IL-23, tumor necrosis factor (TNF)-α and CXC chemokine ligand 1 (CXCL1) of serum and colon tissue were detected by MSD multifactorial assay.The apoptosis of local cells in colon tumor was observed by TUNEL staining. Cell proliferation in colon tumor was observed by immunohistochemistry., Results: Compared with the normal group, the colon length was significantly shortened ( P <0.05) and the colon mass was significantly increased ( P <0.001) in the model group, the contents of IL-1β, IL-6, TNF-α, IL-17A and CXCL1 of serum and colon tissue were significantly increased ( P <0.05, P <0.01, P <0.001), and the content of IL-23 was increased in colon tissue ( P <0.05) in the model group. Compared with the model group, the colon mass was decreased ( P <0.05) and the contents of IL-1β, IL-6, TNF-α and IL-17A in serum were decreased ( P <0.05), while the contents of IL-17A, CXCL1 and IL-23 in colon tissue were decreased ( P <0.05) in the EA group, the percentage of local apoptotic cells in the EA group was increased ( P <0.001), the percentage of PCNA positive cells was decreased ( P <0.001), the number of tumors and the tumor volume were significantly decreased ( P <0.01, P <0.05). The contents of IL-6, TNF-α, IL-17A and IL-23 in serum of CRC mice were positively correlated with tumor burden ( P <0.05).The contents of IL-1β, TNF-α, CXCL1 and IL-23 in colon tissue of CRC mice were positively correlated with tumor burden ( P <0.05)., Conclusion: Electroacupuncture at ST36 can inhibit the inflammatory response of AOM/DSS inflammatory associated CRC mice and delay the "inflammation-cancer transformation" of colon.

Objective: To explore the effect of thoracic paravertebral anesthesia (TPVB) on prognosis of patients undergoing resection of lung cancer., Methods: This study was conducted among the patients undergoing surgical resection of primary lung cancer under general anesthesia or TPVB combined with general anesthesia (TPVB+GA) between January, 2017 and May, 2018.The patients were enrolled in TPVB+GA group and GA group (control group) using a propensity score matching (PSM) method at the ratio of 1:2 based on their baseline characteristics.The clinical parameters, 5-year overall survival (OS), progression-free survival (PFS) and intraoperative dosage of opioids were compared between the two groups to assess the impact of TPVB on prognosis of the patients., Results: Forty-seven patients were enrolled in TPVB+GA group and 94 in the control group.Kaplan-Meier survival analysis showed a significantly prolonged PFS in the patients with TPVB+GA (log-rank P =0.034), with an odds ratio (OR) of 0.45(95% CI : 0.33-0.89).Consistently, univariate and multivariate Cox regression analyses identified TPVB as an independent protective prognostic factor for patients with lung cancer resection ( P =0.002, OR=0.33, 95% CI : 0.16-0.66).Cox regression analyses indicated that a lower intraoperative dose of remifentanil was significantly correlated with a longer PFS of the patients following lung cancer resection ( P =0.017, OR=0.47, 95% CI : 0.25-0.87).Chi-square test confirmed that TPVB, but not general anesthesia, significantly reduced intraoperative dose of remifentanil, indicating a possible synergistic effect of TPVB with opioids to affect the survival of the patients., Conclusion: TPVB can prolong the survival time and improve the prognosis of the patients undergoing surgical resection of lung cancer.

Objective: To summarize the genetic characteristics of 671 Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD)., Methods: Clinical data of the pedigrees were collected. Multiplex PCR, multiple ligation dependent probe amplification (MLPA), next generation sequencing (NGS), Sanger sequencing and long read sequencing were used to detect the variant of DMD gene in the probands and their mothers, and prenatal diagnosis was provided for high risk pregnant women., Results: Among 178 pedigrees analyzed by multiplex PCR, 44 variants of the DMD gene were detected, with the genetic diagnosis attained in 110 pedigrees. Among 493 pedigrees analyzed by MLPA in combination with NGS or Sanger sequencing, 294 pathogenic/possible pathogenic variants were identified, among which 45 were unreported previously, and the genetic diagnosis attained in 484 pedigrees. Structural variants of the DMD gene were identified in two pedigrees by long-read sequencing. Among 444 probands, 341 have inherited the DMD gene variant from their mothers (76.8%). Among 390 women with a high-risk, 339 have opted to have natural pregnancy and 51 chose preimplantation genetic testing for monogenetic disease (PGT-M). The detection rate of neonatal patients and carriers following natural pregnancy was significantly higher than that for PGT-M., Conclusion: Combined application of MLPA, NGS, Sanger sequencing and long-read sequencing is an effective strategy to detect DMD/BMD. PGT-M can effectively reduce the risk of fetuses. Above finding has expanded the spectrum of DMD gene variants and provided a basis for reproductive intervention for pregnancies with a high risk for DMD/BMD.

Objective: To explore the combined pro-apoptosis effect of HSP90 inhibitor BIIB021 and chloroquine (CQ) in chronic myeloid leukemia (CML) cells bearing T315I mutation and its mechanism., Methods: The p210-T315I cells were divided into 4 groups by different treatment: control, BIIB021, CQ, and BIIB021 + CQ. After treated with BIIB021 or/and CQ for 24 hours, Annexin V/PI binding assay was used to detect apoptosis rates of CML cells. DAPI staining was used to observe nuclear fragmentation, and Western blot was used to detect the expression of caspase 3, PARP (apoptosis related proteins) and p62, LC3-I/II (autophagy related proteins). P210-T315I cells were inoculated subcutaneously into mice and CML mouse models were established. The mice in treatment groups were injected with BIIB021 and/or CQ while mice in control group were treated with PBS and normal saline. The tumor volume of mice was measured every 4 days, and protein level of cleaved-caspase 3 and LC3-II in tumor tissue were detected by immunohistochemistry., Results: The results showed that BIIB021 induced apoptosis of CML cells in a dose-dependent manner ( r=0.91). CQ could enhance the apoptosis-inducing effect of BIIB021. Flow cytometry analysis results showed that the apoptosis rate of p210-T315I cells in combination group was higher than that in BIIB021 or CQ only group (P<0.05). DAPI staining showed nuclear fragmentation in combination group could be observed more obviously. Western blot analysis showed that BIIB021 could induce LC3-I to convert to LC3-II and decrease p62 protein levels (P<0.05). Moreover, the combination group had higher expression of LC3-II, p62 (P<0.05), activated PARP and activated caspase 3 than BIIB021 only group (P<0.05). Besides, experiment in vivo showed the mean tumor volume in co-treatment group was lower than that in single drug group (P<0.01). Immunohistochemistry of tumor tissue also showed the protein level of cleaved-caspase 3 and LC3-II in combined group was higher than that in BIIB021 only group., Conclusion: HSP90 inhibitor BIIB021 induced significant apoptosis of CML cells bearing T315I both in vivo and in vitro. CQ can enhance this effect probably by autophagy inhibition.

Objective: To investigate the changes of skin temperature, blood infusion and inflammatory cytokines of cutaneous tissue in the sensitized area of colitis model rats, as well as the relationship between sensory and sympathetic nerves and the formation of sensitized area, and to initially reveal the partial physical - chemical characteristics of the sensitized area in the colitis model rats., Methods: Thirty-five male SD rats were randomly divided into a control group ( n =10), a model group ( n =18) and a guanethidine group ( n =7). 5% dextran sulfate sodium (DSS) was adopted for 6-day free drinking to establish colitis model in the model group and the guanethidine group. On day 6 and 7, in the guanethidine group, guanethidine solution (30 mg/kg) was injected intraperitoneally for sympathetic block. On day 7, after injection of evans blue (EB) solution, the EB extravasation areas on the body surface were observed to investigate the distribution and physical-chemical characteristics of the sensitized area. The control area was set up, 0.5 cm away from the sensitized area, and with the same nerve segment innervation. Disease activity index (DAI) score of rats was compared between the normal group and the model group, and the morphological changes in the colon tissue were investigated with HE method. Using infrared thermal imaging technology and laser speckle flow imaging technology, skin temperature and blood infusion were determined in the sensitized area and the control area of the rats in the model group. Immunofluorescence technique was adopted to observe the expression levels of the positive nerve fibers of substance P (SP), calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH), and the correlation with blood vessels; as well as the expression levels of SP positive nerve fibers/tryptase + mast cells, and tryptase + mast cells/5-hydroxytryptamine (5-HT) in skin tissue in the sensitized area and the control area of the rats in the model group. MSD multi-level factorial method and ELISA were applied to determine the contents of pro-inflammatory and anti-inflammatory cytokines (e.g. TNF-α, IL-1β, IL-6, IL-4 and IL-10) and anti-inflammatory substance corticosterone (CORT)., Results: Sensitization occurred at the T 12 -S 1 segments of the colitis model rats, especially at L 2 -L 5 segments. Compared with the normal group, DAI score was increased in the rats of the model group ( P <0.05), and the colonic mucosal damage was obvious, with the epithelial cells disordered, even disappeared, crypt destructed, submucosal edema and a large number of inflammatory cells infiltrated. In comparison with the control area, the skin temperature and blood infusion were increased in the sensitized area of the model group ( P <0.05, P <0.01); as well as the expression levels of the positive nerve fibers of SP, CGRP and TH of skin tissue ( P <0.05), which was specially distributed in peripheral vessels, the expression levels of SP positive nerve fibers/tryptase + mast cells, and tryptase + mast cells/5-HT of the skin tissue were all expanded ( P <0.05) in the sensitized area of the model group. Compared with the model group, the number of sensitized areas was reduced in the guanethidine group ( P <0.05). In comparison with the control area of the model group, in the sensitized area, the contents of pro-inflammatory cytokines, e.g. TNF-α, IL-1β and IL-6, and the anti-inflammatory substance CORT of skin tissue were all increased ( P <0.05); and the contents of IL-6 and TNF-α were negatively correlated with CORT ( P <0.05)., Conclusion: The sensitized areas on the body surface of colitis rats are mainly distributed in the L 2 -L 5 segments. Sensory and sympathetic nerves are involved in the acupoint sensitization, and the sensitized areas may have the dynamic changes in pro-inflammatory and anti-inflammatory substances.

Objective To investigate the role of connexin 43 (Cx43) in the autophagy of rat thoracic aortic vascular smooth muscle cells (VSMCs) induced by oxidized low-density lipoprotein (ox-LDL). Methods The primary VSMCs were identified by immunofluorescence cytochemical staining of α-smooth muscle actin (α-SMA). After ox-LDL treatment, the foam cells were identified by oil red O staining; the expression of microtubule associated protein 1 light chain 3 (LC3) protein in VSMCs treated with 0, 40, 80, 160 μg/mL ox-LDL for 0, 6, 12, 24 hours and the expression of Cx43 protein treated with 80 μg/mL ox-LDL for 24 hours were detected by Western blotting. VSMCs were randomly divided into control group, ox-LDL group, and ox-LDL combined with Cx43 specific antagonist Gap26 group to detect the expressions of LC3 and beclin 1 by Western blotting. Results The positive rate of α-SMA in the isolated cells was more than 95%. The oil red O positive cells in ox-LDL treated cells significantly increased, ox-LDL decreased the ratio of LC3II/LC3I and the expression of beclin 1 protein in a concentration- and time-dependent manner, and the expression of Cx43 protein was significantly increased. After administration of Gap26, the ratio of LC3II/LC3I and the expression of beclin 1 protein were up-regulated. Conclusion Cx43 inhibits autophagy of VSMCs induced by ox-LDL. Cx43 inhibits ox-LDL induced autophagy.

Critical ultrasonography is widely used in ICU and has become an indispensable tool for clinicians. However, besides operator-dependency of critical ultrasonography, lack of standardized training mainly result in the physicians' heterogenous ultrasonic skill. Therefore, standardized training as well as strict quality control plays the key role in the development of critical ultrasonography. We present this quality control standards to promote better development of critical ultrasonography.

Objective: To investigate the effect of 275 nm and 310 nm ultraviolet irradiation on ovariectomized rats' bone metabolism., Methods: Twenty four 3-month-old female Sprague-Dawley (SD) rat were randomly divided into control group, sham operated group, 275 nm ultraviolet (UV) irradiation group and 310 nm UV irradiation group. Each group contained 6 rats. The rats in the two irradiation groups were treated with bilateral ovariectomy. The rats in sham operated group received sham operation (They were given the same back incision and a bit of par-ovarian fat were removed). Control group received no disposition. About 24 weeks after operation, all the rats received detailed bone mineral density (BMD) detection again. Detection regions include cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur. Next, osteopenia rats in 275 nm irradiation group were UV irradiated 275 nm with fixed illumination intensity (15 μW/cm 2 ) everyday for 16 weeks. The osteopenia rats in 310 nm irradiation group were UV irradiated 310 nm with fixed illumination intensity (15 μW/cm 2 ) everyday for 16 weeks. The backs of the rats were shaved regularly as irradiation area (6 cm×8 cm). After 16-week irradiation, all the rats' BMD of cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur were measured. At the end of the trial, all the rats' blood specimens were obtained and serum 25(OH)D, procollagen type Ⅰ N-peptide (PINP) and osteocalcin (OC) were measured., Results: Compared with control group [(238.78±26.74) mg/cm 3 ], the BMD of the whole body were significantly lower in 275 nm [(193.34±13.28) mg/cm 3 ] and 310 nm [(191.19±18.48) mg/cm 3 ] irradiation groups ( P =0.002, P =0.001). There were no significant difference between sham operated group [(227.20±14.32) mg/cm 3 ] and control group. After 16-week ultraviolet irradiation, the BMD of the whole body were significantly increased in 275 nm [(193.34±13.28) mg/cm 3 vs . (221.68±25.52) mg/cm 3 , P =0.005] and 310 nm groups [(191.19±18.48) mg/cm 3 vs . (267.48±20.54) mg/cm 3 , P < 0.001] after corresponding irradiation. The BMD of the four body regions (lumbar vertebra, proximal femur, mid femur and distal femur) had significantly increased after irradiation in 275 nm irradiation group. For 310 nm irradiation group, the BMD in cervical vertebra, lumbar vertebra, proximal femur, mid femur and distal femur also had increased significantly after 310 nm ultraviolet irradiation. The concentration of serum 25(OH)D and OC was higher in 275 nm irradiation group than in control group [(46.78±5.59) μg/L vs . (21.32±6.65) μg/L, P =0.002;(2.05±0.53) U/L vs . (1.32±0.07) U/L, P =0.022]. Compared with the control, the concentration of serum 25(OH)D [(58.05±12.74) μg/L], OC [(2.04±0.53) U/L] and PINP [(176.16±24.18) U/L] was significantly higher ( P < 0.001, P =0.015, P =0.005) in 310 nm irradiation group. However, there were no significantly difference between sham operated group and the control., Conclusion: Both 275 nm and 310 nm ultraviolet could improve rats' vitamin D synthesis. Both 275 nm and 310 nm ultraviolet could improve osteopenia rats' bone condition. The irradiation of 310 nm might be more effective on bone condition improvement.

To provide references for the diagnosis and treatment of congenital granular cell tumor (CGCT), by comprehensive analysis of the clinical data, histopathological and immunohistochemical results. Patients with CGCT were involede, from March 2015 to November 2020, at the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Zhengzhou University. A total of 6 children, aged 3-16 days, 1 male and 5 female, 5 maxillary and 1 mandibular, with maximum tumor diameter of 6-70 mm, were included. The lesions of CGCT were single and connected to the alveolar ridge by a pedicle. The surface of the tumor was covered with a vascular network, and two cases had ulcers on the surface of the tumor. All 6 cases had the tumor removed surgically and there was no recurrence or metastasis in the follow-up visit. Although CGCT is rare, it is a benign tumor and generally does not recur or metastasize after surgery, and has a good prognosis. The prenatal imaging, clinical manifestations after delivery, pathological characteristics and immunohistochemical analyses may provide reference for early diagnosis and treatment of CGCT.

Objective: To determine the carrier rate for 21 inherited metabolic diseases among a Chinese population of childbearing age., Methods: A total of 897 unrelated healthy individuals (including 143 couples) were recruited, and DNA was extracted from their peripheral blood samples. Whole exome sequencing (WES) was carried out to screen potential variants among 54 genes associated with 21 inherited metabolic diseases. Pathogenic and likely pathogenic variants and unreported loss-of-function variants were analyzed., Results: One hundred fourty types of pathogenic/likely pathogenic variants (with an overall number of 183) and unreported loss-of-function variants were detected, which yield a frequency of 0.20 per capita. A husband and wife were both found to carry pathogenic variants of the SLC25A13 gene and have given birth to a healthy baby with the aid of preimplantation genetic diagnosis. The detected variants have involved 40 genes, with the most common ones including ATP7B, SLC25A13, PAH, CBS and MMACHC. Based on the Hardy-Weinberg equilibrium, the incidence of the 21 inherited metabolic diseases in the population was approximately 1/1100, with the five diseases with higher incidence including citrullinemia, methylmalonic acidemia, Wilson disease, glycogen storage disease, and phenylketonuria., Conclusion: This study has preliminarily determined the carrier rate and incidence of 21 inherited metabolic diseases among a Chinese population of childbearing age, which has provided valuable information for the design of neonatal screening program for inherited metabolic diseases. Pre-conception carrier screening can provide an important measure for the prevention of transmission of Mendelian disorders in the population.