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Objective To evaluate the proprioceptive and clinical function of the knee joint after anterior cruciate ligament reconstruction (ACLR) with various amounts of remnant preserved with as few confounding factors as possible. Methods This retrospective study included 46 patients who underwent ACLR with remnant preservation between March 2013 and February 2019. These patients had less than 6 months injury‐to‐surgery interval and no concomitant injuries. The researchers divided these subjects into two groups based on the length of the remnant preserved after ACLR, with group A defined as having more than 1/3 of the original length preserved and group B defined as less than 1/3 of the original length preserved. Clinical scores were obtained using the Lysholm knee scoring scale and the Tegner activity scale. The Lysholm score was calculated preoperatively, at 3, 6, and 12 months postoperatively, and at the last follow up. The Tegner score was calculated preoperatively, at 12 months postoperatively and at the last follow up. Anterior laxity was measured using the KT2000 arthrometer preoperatively and at 12 months postoperatively. Proprioceptive function was evaluated through reproduction of passive positioning (RPP) and threshold to detection of passive motion (TDPM). Both RPP and TDPM were measured at the angle of 15° at 3, 6, and 12 months postoperatively. Unpaired t‐tests were performed to investigate the difference in each parameters between the two groups. Results In the present study, 20 patients were classified into group A and 26 into group B. All patients were followed up for an average of 34.70 ± 12.79 months. All 46 patients were satisfied with the outcome of the surgery and no complications were reported at the end of the study. No significant differences were found between the two groups in terms of the Lysholm score and anterior laxity by KT2000 at all time points. The Tegner score was significantly higher in group A at 12 months postoperatively and at the final follow‐up. In addition, group A's RPP was significantly better than that of group B's when tested at the angles of 15° and 30° at 3 months postoperatively, and at the angle of 15° at 6 months postoperatively. Group A's TDPM was also significantly better than that of group B's at all three tested angles at 3 months postoperatively, and at the angle of 15° at 6 months postoperatively. Conclusion Patients with ACLR with more than 1/3 of the original length preserved demonstrated a higher activity level 12 months postoperatively and better proprioceptive function at 15° of extension at 3 and 6 months postoperatively.

Locally recurrent rectal cancer (LRRC) leads to a poor prognosis and appears as a clinically predominant pattern of failure. In this research, whole-exome sequencing (WES) was performed on 21 samples from 8 patients to search for the molecular mechanisms of LRRC. The data was analyzed by bioinformatics. Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) were performed to validate the candidate genes. Immunohistochemistry was used to detect the protein expression of LEF1 and CyclinD1 in LRRC, primary rectal cancer (PRC), and non-recurrent rectal cancer (NRRC) specimens. The results showed that LRRC, PRC, and NRRC had 668, 794, and 190 specific genes, respectively. FGFR1 and MYC have copy number variants (CNVs) in PRC and LRRC, respectively. LRRC specific genes were mainly enriched in positive regulation of transcription from RNA polymerase II promoter, plasma membrane, and ATP binding. The specific signaling pathways of LRRC were Wnt signaling pathway, gap junction, and glucagon signaling pathway, etc. The transcriptional and translational expression levels of genes including NFATC1, PRICKLE1, SOX17, and WNT6 related to Wnt signaling pathway were higher in rectal cancer (READ) tissues than normal rectal tissues. The PRICKLE1 mutation (c.C875T) and WNT6 mutation (c.G629A) were predicted as “D (deleterious)”. Expression levels of LEF1 and cytokinin D1 proteins: LRRC > PRC > NRRC > normal rectal tissue. Gene variants in the Wnt signaling pathway may be critical for the development of LRRC. The present study may provide a basis for the prediction of LRRC and the development of new therapeutic drugs.

Both ligament-advanced reinforcement system (LARS) and hamstring tendon autograft can serve as grafts for posterior cruciate ligament (PCL) reconstruction. However, few studies have compared the effectiveness of these two approaches. This study therefore aimed to compare the clinical efficacy of arthroscopic reconstruction of the PCL using either the LARS or hamstring tendon autograft.A total of 36 patients who underwent PCL reconstruction were retrospectively analyzed. Within this cohort, 15 patients received a reconstruction using the LARS (LARS group) and 21 using the hamstring tendon autograft (HT group).The pre- and post-operative subjective scores and knee stability were evaluated and the patients were followed up for a period of 2 to 10.5 years (4.11±2.0 years on average). The last follow-up showed that functional scores and knee stability were significantly improved in both groups (P0.05). Six months after operation, Lysholm scores and IKDC subjective scores were higher in the LARS group than in the HT group (P0.05). Nonetheless, the last follow-up showed no significant differences in the functional scores or the posterior drawer test between the two groups (P0.05). In the LARS and HT groups, 12 and 9 patients, respectively exhibited KT1000 values3 mm, with the difference being statistically significant (P0.05). In the HT group, the diameter of the four-strand hamstring tendon was positively correlated with height (P0.05), which was 7.37±0.52 mm in males and 6.50±0.77 mm in females (P0.05).Both LARS and hamstring tendon approaches achieved good efficacy for PCL reconstruction, but patients in the LARS group exhibited faster functional recovery and better knee stability in the long term. LARS is especially suitable for those who hope to resume activities as early as possible.

Objectives This study aims to explore the prevalence of sexual satisfaction among Chinese cancer survivors, and explore the association of sexual satisfaction with comorbidity and lifestyle factors. Methods A cross‐sectional study was performed among 3996 Chinese cancer survivors recruited at Shanghai Cancer Rehabilitation Club from March to April 2017. Data were collected through self‐reported questionnaires. The questionnaire includes information about demographic, cancer characteristics, comorbidities, lifestyle factors, and sexual satisfaction. Sexual satisfaction was measured by a single‐item scale. The distribution of sexual satisfaction among different demographic and cancer characteristics was compared using the chi‐squared test. Logistic regression models were conducted to assess the effects of lifestyle factors, comorbidities on sexual satisfaction after adjustment for demographic and cancer characteristics. Results More than 40% of male and female cancer survivors reported no sexual satisfaction. Sexual satisfaction of cancer survivors is significantly associated with both the number and the type of comorbidities. Heart disease, musculoskeletal system disease, diabetes, and hyperlipidemia are the comorbidities significantly associated with sexual satisfaction of cancer survivors. Lifestyle factors other than smoking, including exercise or fitness, drinking alcohol, and eating fruits and vegetables are significantly correlated with sexual satisfaction. Besides, all of the above associations show gender differences. In addition, demographic characteristics include sex, age, marital status, living status, and average monthly income are also significantly associated with sexual satisfaction of cancer survivors. Conclusion Comorbidity and lifestyle factors are associated with sexual satisfaction of cancer survivors, and the associations show gender differences. Improving the lifestyles of cancer survivors, and controlling and reducing their comorbidities are important for improving their sexual satisfaction., This study aims to investigate the prevalence of sexual satisfaction among Chinese cancer survivors, and explore the association of sexual satisfaction with comorbidity and lifestyle factors. Comorbidity and lifestyle factors are associated with sexual satisfaction of cancer survivors, and the associations show gender differences. Improving the lifestyles of cancer survivors, and controlling and reducing their comorbidities are important for improving their sexual satisfaction.

To evaluate clinical efficacy of single-tunnel double-line technique with tendoscopy in treating tibial intercondylar eminence fractures.From January 2016 to April 2020, 22 patients with tibial intercondylar eminence fractures were admitted, including 14 males and 8 females with a mean age of (34.8±5.9) years old ranging from 26 to 45 years old. The mean duration from injury to surgery was(11.2±4.1) days(ranged, 5 to15 d). All patients were treated with arthroscopic single-tunnel double-line technique. The fracture healing was evaluated according to X-ray. The Lysholm score, IKDC 2000 score and the anterior drawer test were used to evaluate efficacy before operation and at the latest follow-up.All patients were followed up, and the duration ranged from 12 to 75 months, with an average of(34.6±13.0) months. Lysholm score was (89.60±2.89) points at the latest follow-up, showing significant difference when compared with preoperative score which was (30.80±9.55)points(Single-channel double-line technique could effectively fix bone block of intercondylar eminence with advantage of easy operation and minimally invasive, which could be applied to various types of tibial intercondylar eminence fractures.

Background To introduce a treatment option: dacryoendoscopy-assisted incision of Hasner’s valve under nasoendoscopy and assess its efficacy in treating membranous congenital nasolacrimal duct obstruction (CNLDO) in children older than 1 year with history of initial probing failure. Methods 52 eyes of 43 children with membranous CNLDO who underwent dacryoendoscopy-assisted incision of Hasner’s valve under nasoendoscopy between May 2012 and October 2020 were enrolled in this retrospective study. All participants were older than 1 year and all the eyes had gone through probing at least once but still had symptoms of epiphora and discharge. Surgical success was defined as a normal fluorescein dye disappearance test (FDDT) and the absence of pre-operation complaints, including epiphora, muco-purulent discharge, increased tear lake or the symptoms of acute infection such as acute dacryocystitis. Patients’ demographics, clinical features and follow-up outcomes were evaluated. Results Of all these operated cases, surgical success was achieved in 52/52 eyes without any early or late complications. The overall success rate was 100%. Conclusions Dacryoendoscopy-assisted incision of Hasner’s valve under nasoendoscopy is an effective and minimally invasive surgical treatment in membranous CNLDO patients with initial probing failure.

Intracerebral hemorrhage (ICH) is the second largest type of stroke, with high mortality and morbidity, and most patients have severe sequelae. Brain injury induced by ICH includes primary damage and secondary damage, and the secondary brain injury is the main reason of neurological impairment. The hallmark of secondary brain injury is cell death. Necroptosis is a type of the cell death and plays vital roles in various neurological diseases, but the roles of necroptosis in ICH are still not fully known. Microglia cell is the type of immune cell, plays protective roles in nerve damage and modulates the activity of neurons through secreting exosomes. Exosome-contained miRNAs are also involved in the regulating neuronal activity. However, the roles and the mechanisms of microglia-secreted exosomes miRNAs in ICH neurons necroptosis need to further explore. In this study, ICH model was construct in rats and cells. Injury of cells in brain was detected by PI staining. Necroptosis in rats and cells was detected by western blot and flow cytometry. The expression of miR-383-3p was detected by RT-qPCR. The roles of activated microglia-secreted exosomes and exosome-contained miR-383-3p were detected through co-culturing medium or exosomes with neurons. The target gene of miR-383-3p was determined by luciferase assay and the expression of target gene was detected by western blot. Rescue experiments were used to confirm the mechanism of miR-383-3p in neurons necroptosis. The miR-383-3p role was verified in vivo through injecting miR-383-3p mimic into ICH rats. Here, we found that the necroptosis of neurons was increased in ICH rats through detecting the expression of RIP1 and RIP3 and PI staining. Microglia that activated by ICH promote neurons necroptosis through secreting exosomes and transferring miR-383-3p into neurons. In mechanism, miR-383-3p negatively regulated the expression of ATF4 and then promoted the necroptosis of neurons. Overall, our results provide a novel molecular basis to neurons necroptosis in ICH and may provide a new strategy to retard the secondary brain injury of ICH.

Aim To assess the prevalence, related factors, and strategies for the prevention and treatment of pressure ulcers (PUs) in nursing homes in eastern China. Materials and methods In this cross-sectional multicenter survey, assessments of 1158 residents in nine nursing homes in eastern China were conducted on a single day in August of 2019. Results Of the 1158 residents, 56 (4.8%) had at least one PU. Most of the identified PUs were classified as stage 3 (39.3%) and developed at home (55.4%). By multiple regression analysis, eating mode, bed-bound, and Braden score were significant association with the development of PUs in nursing homes. Conclusions The prevalence of PUs in this study was similar to that reported by previous international studies. The implementation of measures for the prevention and treatment of PUs is insufficient in nursing homes in eastern China. Further, this study raised the issue of the lack of measures to prevent the development of PUs at home.

The immunosuppressive microenvironment that is shaped by hepatic metastatic pancreatic ductal adenocarcinoma (PDAC) is essential for tumor cell evasion of immune destruction. Neutrophils are important components of the metastatic tumor microenvironment and exhibit heterogeneity. However, the specific phenotypes, functions and regulatory mechanisms of neutrophils in PDAC liver metastases remain unknown. Here, we show that a subset of P2RX1-negative neutrophils accumulate in clinical and murine PDAC liver metastases. RNA sequencing of murine PDAC liver metastasis-infiltrated neutrophils show that P2RX1-deficient neutrophils express increased levels of immunosuppressive molecules, including PD-L1, and have enhanced mitochondrial metabolism. Mechanistically, the transcription factor Nrf2 is upregulated in P2RX1-deficient neutrophils and associated with PD-L1 expression and metabolic reprogramming. An anti-PD-1 neutralizing antibody is sufficient to compromise the immunosuppressive effects of P2RX1-deficient neutrophils on OVA-activated OT1 CD8+ T cells. Therefore, our study uncovers a mechanism by which metastatic PDAC tumors evade antitumor immunity by accumulating a subset of immunosuppressive P2RX1-negative neutrophils., Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive metastatic disease characterized by an immunosuppressive microenvironment. Here the authors show that a subset of P2RX1-negative neutrophils with immunosuppressive properties accumulate in PDAC metastatic liver tissues and promote tumor growth.

Currently, homosexual transmission has become one of the main routes of HIV-1 spread in China. Furthermore, about 80% Chinese men, who have sex with men (MSM), feel forced to enter eventually into heterosexual marriages due to the Chinese traditional marriage culture, which may cause HIV-1 infection in families. In this study, we identified HIV-1 transmission in a family and the direction of HIV-1 transmission from a MSM to his wife and infant, which indicated Chinese MSM may have become a potential bridge of HIV-1 transmission to their wives and children. Therefore, we need to develop more effective defence measures to prevent the spread of HIV-1 in MSM families in China.

Bone has a remarkable potential for self-healing and repair, yet several injury types are non-healing even after surgical or non-surgical treatment. Regenerative therapies that induce bone repair or improve the rate of recovery are being intensely investigated. Here, we probed the potential of bone marrow stem cells (BMSCs) engineered with chemically modified mRNAs (modRNA) encoding the hBMP-2 and VEGF-A gene to therapeutically heal bone. Induction of osteogenesis from modRNA-treated BMSCs was confirmed by expression profiles of osteogenic related markers and the presence of mineralization deposits. To test for therapeutic efficacy, a collagen scaffold inoculated with modRNA-treated BMSCs was explored in an in vivo skull defect model. We show that hBMP-2 and VEGF-A modRNAs synergistically drive osteogenic and angiogenic programs resulting in superior healing properties. This study exploits chemically modified mRNAs, together with biomaterials, as a potential approach for the clinical treatment of bone injury and defects., Geng et al. evaluate bone marrow stem cell (BMSC)-based system to deliver modified RNAs of BMP-2 and VEGF to enhance bone regeneration. They test its therapeutic efficacy in vivo on a rat skull defect model by inoculating these BMSCs in a collagen scaffold. This construct synergistically drives osteogenic and angiogenic pathways and can be a new approach for clinical treatment of bone injuries and defects.

We sought to compare the clinical and radiologic outcomes after anterior cervical surgery between zero-profile (Zero-P) cage and plate-cage construct (PCC).One-hundred and sixteen patients with single-level cervical disk herniation who underwent anterior cervical diskectomy and fusion between May 2015 and March 2017 were enrolled. They were divided into a Zero-P group (61 cases) and a PCC group (55 cases). At 1, 6, 12, and 24 months after the operation, routine follow-up evaluation was recommended including visual analog scale score and Japanese Orthopaedic Association score. The lateral x-ray film was performed at 1 and 24 months postoperatively.All 116 patients successfully completed the operation and achieved bone fusion. While there was no significant difference in the amount of bleeding between the 2 groups, the operation time of the Zero-P group was significantly shorter than that of the PCC group with statistically difference. The visual analog scale score and Japanese Orthopaedic Association score of the 2 groups at each follow-up interval postoperatively were significantly improved compared with that before operation; the difference was statistically significant (P0.05, respectively). While all the C2-7 cervical curvature, segmental Cobb angle, and height of adjacent vertebral body were lost at the 24-month follow-up, the significant difference was observed in the Zero-P group (P0.05, respectively).Compared with the Zero-P system, the PCC system provides a comparable clinical outcome. Although it showed the disadvantages in controlling the operation time and surgical bleeding, the radiologic outcome was better at the 2-year follow-up.

Objective Ventriculostomy-related infection (VRI) is associated with potential serious morbidity, extended hospitalization duration, increased health care costs, and mortality. We assessed the effectiveness of a pragmatic risk-stratification pathway for external ventricular drain (EVD) management, allowing for surgical decision making, in reducing the rate of VRIs. Methods Two studies were performed concurrently. A retrospective audit of EVD infection rates and outcomes in our unit across 3 hospitals was conducted from January to December 2014. The second prospective study compared the same variables during the implementation of the EVD pathway across the 3 sites from January 2015 to December 2016. Results The number of patients requiring EVDs increased from 2014 to 2016 (165 vs. 189 vs. 197 patients, respectively), with a significant increase in patients with intraventricular hemorrhage (P = 0.009). Despite increasing risk, overall EVD infections decreased during the implementation period, from 4.8% (8/165) in 2014 to 3.7% in 2015 (7/189) and 2.0% in 2016 (4/197, P = 0.33). In 2 sites (site 1, 2.0% vs. 2.1% vs. 1.9%, and site 2, 4.7% vs. 5.0% vs. 5.3%), transition to the EVD risk-stratification pathway maintained already low infection rates; in site 3, EVD infections decreased from 6.8% (5/73) to 3.9% (4/102) and 0% (0/86, P = 0.06). Conclusions The introduction of a pragmatic evidence-based risk-stratification pathway, in which different options for EVD management are incorporated, results in low EVD infection rates across a multisite institutional practice. Our results are comparable to published protocols involving the implementation of standard care bundles and/or antibacterial EVDs alone, in reducing VRIs.

Rationale: Endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) is an endoplasmic reticulum (ER) luminal glycoprotein that has a role in the formation of disulfide bonds of secreted proteins and membrane proteins. Emerging data identify ERO1L as a tumor promoter in a wide spectrum of human malignancies. However, its molecular basis of oncogenic activities remains largely unknown. Methods: Pan-cancer analysis was performed to determine the expression profile and prognostic value of ERO1L in human cancers. The mechanism by which ERO1L promotes tumor growth and glycolysis in pancreatic ductal adenocarcinoma (PDAC) was investigated by cell biological, molecular, and biochemical approaches. Results: ERO1L was highly expressed in PDAC and its precursor pancreatic intraepithelial neoplasia and acts as an independent prognostic factor for patient survival. Hypoxia and ER stress contributed to the overexpression pattern of ERO1L in PDAC. ERO1L knockdown or pharmacological inhibition with EN460 suppressed PDAC cell proliferation in vitro and slowed tumor growth in vivo. Ectopic expression of wild type ERO1L but not its inactive mutant form EROL-C394A promoted tumor growth. Bioinformatics analyses and functional analyses confirmed a regulatory role of ERO1L on the Warburg effect. Notably, inhibition of tumor glycolysis partially abrogated the growth-promoting activity of ERO1L. Mechanistically, ERO1L-mediated ROS generation was essential for its oncogenic activities. In clinical samples, ERO1L expression was correlated with the maximum standard uptake value (SUVmax) in PDAC patients who received 18F-FDG PET/CT imaging preoperatively. Analysis of TCGA cohort revealed a specific glycolysis gene expression signature that is highly correlated with unfolded protein response-related gene signature. Conclusion: Our findings uncover a key function for ERO1L in Warburg metabolism and indicate that targeting this pathway may offer alternative therapeutic strategies for PDAC.

Exercise training is believed to have a positive effect on cardiac hypertrophy after hypertension. However, its mechanism is still not fully understood. Herein, our findings suggest that heat shock transcription factor 1 (HSF1) improves exercise‐initiated myocardial angiogenesis after pressure overload. A sustained narrowing of the diagonal aorta (TAC) and moderately‐ intense exercise training protocol were imposed on HSF1 heterozygote (KO) and their littermate wild‐type (WT) male mice. After two months, the cardiac function was assessed using the adaptive responses to exercise training, or TAC, or both of them such as catheterization and echocardiography. The HE stains assessed the area of myocyte cross‐sectional. The Western blot and real‐time PCR measured the levels of expression for heat shock factor 1 (HSF1), vascular endothelial growth factor (VEGF) and hypoxia inducible factor‐1 alpha (HIF‐1α) in cardiac tissues. The anti‐CD31 antibody immunohistochemical staining was done to examine how exercise training influenced cardiac ontogeny. The outcome illustrated that exercise training significantly improved the cardiac ontogeny in TAC mice, which was convoyed by elevated levels of expression for VEGF and HIF‐1α and preserved the heart microvascular density. More importantly, HSF1 deficiency impaired these effects induced by exercise training in TAC mice. In conclusion, exercise training encourages cardiac ontogeny by means of HSF1 activation and successive HIF‐1α/VEGF up‐regulation in endothelial cells during continued pressure overload.

OBJECTIVE To summarize and analyze the postoperative complications of box-shift osteotomy performed at our center for Chinese orbital hypertelorism patients from 2008 to 2017. METHOD This retrospective study reviews the records of 78 patients with complete medical records and at least 2 years of postoperative follow-up data. Both radiologic and anthropometric assessments were conducted before, 1 month after and 2 years after surgery to evaluate the bony and soft-tissue alterations. Postoperative complications were recorded during hospitalization and at each follow-up visit and divided into 3 groups: acute complications that occurred within 1 month after surgery; early complications that occurred within 6 months after surgery; and long-term complications that occurred within 2 years after surgery. RESULTS Both bony and soft-tissue alterations were significant at 1 month after surgery. The acute complications that occurred in our center included infection (12.8%), cerebrospinal fluid leakage (29.5%), epilepsy (2.6%), and nasal tip skin necrosis (1.3%). The early complications included strabismus (11.5%) and nasolacrimal duct obstruction (3.8%). The long-term complications included insufficient correction (55.1%), palpable metal implants (92.3%) and a drooping nasal tip (33.9%). Due to the insufficient correction and the continued growth of rib graft, the difference in the hypertelorism index and nasal length, between one month and 2 years postoperatively were statistically significant (P

Synchronous resection of primary pancreatic ductal adenocarcinoma (PDAC) and liver metastases in highly selective patients is being accepted based on oncology research progress showing safe surgical outcomes with low morbidity and mortality. We also tried to determine patients who would benefit from the operation.From January 2012 to October 2017, 48 patients who underwent synchronous resection of primary PDAC and liver metastases were retrospectively evaluated. Twenty-three of them underwent oligometastatic synchronous resection.The majority of synchronous resection PDAC patients underwent hepatic wedge resection, and no oligometastatic patient was treated with hemihepatectomy. The median overall survival (OS) of the synchronous resection patients was 7.8 months. Hepatic oligometastatic PDAC patients had a longer OS than that of non-oligometastatic synchronous resection patients, systemic chemotherapy patients and palliative patients (16.1 vs 6.4 months, P = 0.02; 16.1 vs 7.6 months, P = 0.02; 16.1 vs 4.3 months, P 0.0001; respectively). Further analysis showed that localized pancreatic body/tail PDAC had a better OS in oligometastatic patients than in non-oligometastatic synchronous resection patients (16.8 months vs 7.05 months, P = 0.0004) and systemic chemotherapy patients (16.8 months vs 8 months, P = 0.003).Patients with pancreatic body/tail PDAC with liver oligometastases can benefit from synchronous resection.

Tuberculous empyema (TE) is associated with high mortality and morbidity. In the retrospective cohort study, we aimed to find risk factors for TE among pleural tuberculosis (TB) patients. Between July 2011 and September 2015, all culture-confirmed pleural TB patients (474 cases) were enrolled in our study. Empyema was defined as grossly purulent pleural fluid. Demographic and epidemiological data were collected for further analysis. Multivariate logistic regression analysis was used to evaluate risk factors of TE in pleural TB, age–adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated to show the risk. The mean age was 35.7 ± 18.1 years old, males comprised 79.1% of the participants (375 cases). Forty-seven patients (9.9%) were multidrug-resistant TB (MDR-TB), 29 (6.1%) had retreatment TB, 26 (5.5%) had diabetes mellitus. The percentage of empyema patients was 8.9% (42 cases). Multivariate analysis revealed that male (adjusted OR = 4.431, 95% CI: 1.411, 13.919), pleural adenosine deaminase (ADA, >88 U/L) (adjusted OR = 3.367, 95% CI: 1.533, 7.395) and white blood cell (WBC, >9.52 109/L) (adjusted OR = 5.763, 95% CI: 2.473, 13.431) were significant risk factors for empyema in pleural TB, while pulmonary TB (adjusted OR = 0.155, 95% CI: 0.072, 0.336) was the protective factor for the patients. TE remains a serious threat to public health in China. Male sex is a significant risk factor for TE while the presence of pulmonary TB is protective, and high levels of pleural ADA and WBC count could aid in early diagnosis of TE. This finding would help towards reducing the mortality and morbidity associated with TE.

This scoping review mapped out the relevant literature, identified gaps and made suggestions on the influence of cisgender on the health literacy (HL) of the elderly people. This scoping review was guided by the PRISMA-ScR checklist. The databases Wiley Online Library™ and Elsevier™ were searched for academic articles published in the English language between February 2011 and February 2021 that met a pre-set criteria of content. The process of selection of sources of evidence based on screening and eligibility of evidence reduced the initially identified 153 sources of evidence in the searched databases to 14 sources of evidence. The content of these 14 sources of evidence was mapped out on a charting table where data was summarised and synthesised individually and collectively by the authors. Repetitive and irrelevant data were deleted. Identified gaps include the lack of extensive exploration of male and female genders alone as a determinant of HL, how gender may be utilised to encourage elderly men and women to apply HL, how different sociocultural and sociodemographic backgrounds of elderly men and women would require separate academic research, the scarcity of social sciences based research and qualitative research methodologies on the subject as well as the use of mixed-methodologies and longitudinal studies. Future research directions were suggested and limitations of this scoping review are addressed in the discussion.

Ongoing neurovascular dysfunction contributes to type 2 diabetes mellitus (T2DM)-induced cognitive deficits. However, it is not known whether early post onset of T2DM interventions may reduce evolving neurovascular dysfunction and thereby lead to diminution of T2DM-induced cognitive deficits. Using multiple MRI metrics, we evaluated neurovascular changes in T2DM rats treated with exosomes derived from cerebral endothelial cells (CEC-Exos). Two months after induction of T2DM in middle-aged male rats by administration of streptozotocin nicotinamide, rats were randomly treated with CEC-Exos twice weekly or saline for 4 consecutive weeks (n = 10/group). MRI measurements were performed at the end of the treatment, which included cerebral blood flow (CBF), contrast-enhanced T1-weighted imaging, and relaxation time constants T1 and T2. MRI analysis showed that compared with controls, the CEC-Exo–treated T2DM rats exhibited significant elevation of T2 and CBF in white matter and significant augmentation of T1 and reduction of blood-brain barrier permeability in gray matter. In the hippocampus, CEC-Exo treatment significantly increased T1 and CBF. Furthermore, CEC-Exo treatment significantly reduced T2DM-induced cognitive deficits measured by the Morris water maze and odor recognition tests. Collectively, our corresponding MRI data demonstrate that treatment of T2DM rats with CEC-Exos robustly reduced neurovascular dysfunction in gray and white matter and the hippocampus.

Glycogen storage diseases (GSDs) are a group of rare inherited metabolic disorders caused by enzyme deficiencies in glycogen catabolism. The more common type, GSD type Ia, is caused by glucose-6-phosphatase deficiency and often complicated by gout from hyperuricemia. Here, the authors report a rare case of a tophi wound caused by GSD type Ia in a Chinese patient. Difficulties in this case included the control of abnormal blood markers, especially uric acid; removal of tophi deposited in the tissues; restoration of hand function after wound healing; and patient adherence to treatment and follow-up. A multidisciplinary team was set up consisting of experts from the authors' wound care center and the departments of endocrinology, orthopedics, and rehabilitation. The wound healed in 53 days and was followed up for about 7 months. During follow-up, the patient's hand function returned to normal, and no new tophi formed. Because GSDs are a congenital lifelong condition, regular follow-ups are especially important.

Surprisingly, more new unique recombinant forms (URFs) of CRF01_AE/CRF07_BC recombinant viruses were found in Tianjin, China, recently. Here we identified another novel HIV-1 recombinant virus (TJ20170315) isolated from an HIV-1 positive man who has sex with men in Tianjin, China. Phylogenetic analysis of the near full-length genome of TJ20170315 showed that it formed a monophyletic branch within the cluster of CRF01_AE reference sequences. Recombinant analysis showed that the virus kept the CRF01_AE parental backbone, and one CRF07_BC segment was inserted into

Piperine, the major alkaloid constituent of black pepper, has been reported to possess a wide range of pharmacological effects on the central nervous system, including antidepressant, anticonvulsant and anti-ischemic activities. In the present study, we aimed to investigate the therapeutic potential and neuroprotective mechanisms of piperine in an experimental mouse model of sporadic Alzheimer's disease (sAD) induced by intracerebroventricular (ICV) infusion of streptozotocin (STZ). STZ was infused bilaterally at a dose of 1.5 mg/kg/day on day 1 and day 3. From day 8, piperine (2.5-10 mg/kg body weight) was administered intraperitoneally once daily for 15 consecutive days. The locomotor activity and cognitive performance of mice were evaluated using open field test and Morris water maze test, respectively. On day 23, all animals were sacrificed, and the hippocampus was used for biochemical, neurochemical and neuroinflammatory determinations. Our data revealed that the ICV-STZ-infused sAD mouse showed an increased oxidative-nitrosative stress, an altered neurotransmission and an elevated neuroinflammation in hippocampus, as well as significant cognitive deficits. All these alterations can be ameliorated by piperine in a dose-dependent manner. In summary, our findings predict a therapeutic potential of piperine against cognitive deficits in sAD mouse. This effect might be due to its abilities to ameliorate oxidative-nitrosative stress, restore neurotransmission and reduce neuroinflammation.

We conducted a 24-week, randomized, double-blind parallel-controlled trial to test whether buspirone is beneficial to improve cognitive deficits of schizophrenia because it remains unclear. Two hundred patients received in random order either co-treatment buspirone with AAPDs or monotherapy with AAPDs. All patients had been treated with a stable dosage of AAPDs for at least three months. The positive and negative syndrome scale (PANSS), Hamilton Depression Scale-24 (HAMD-24), and 14-item Hamilton Rating Scale for Anxiety (HAMA-14) were used to evaluate clinical symptoms. The short version of Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC) was used to assess neurocognitive function. Social function and family burden were evaluated by Social Disability Screening Schedule (SDSS) and Family Burden Interview Schedule (FBIS). All patients were enrolled at baseline and followed up after 12 and 24 weeks. A total of 196 patients completed the trial, with 99 in the combined treatment group and 97 in the control group. During the intervention, the score of PANSS, HAMD-24, and HAMA-14 decreased slightly without group differences. Repeated measures ANOVA showed significant differences between the two groups in the score of arithmetic, similarities, picture completion, block design, SDSS, and FBIS (P 0.05), but no difference was found with regard to the score of information, digital span test, or digital symbols (P 0.05). In conclusion, co-treatment with buspirone and APPDs outperformed APPDs alone in improving cognitive deficit and reducing family burden of schizophrenia. Buspirone may be a promising candidate for co-treatment of schizophrenia-associated cognitive deficits.

Background: In past magnetic resonance imaging studies, normal participants and schizophrenia patients have usually been compared using imaging processing modes with only one parameter. A more extensive evaluation of significant differences between gray and white matter in Schizophrenic patents was necessary. Methods: Voxel based morphometry was used to separate brain images into gray matter and white matter. Then, the images were mapped to Montreal Neurological Institute space, and DARTEL analytic template was applied for image calibration with statistical parametric mapping. Finally, joint independent component analysis was employed to analyze the gray and white matter of brain images from Schizophrenic patients and normal controls. In this study, joint independent component analysis was used to discriminate clinical differences in magnetic resonance imaging signals between Schizophrenic patients and normal controls. Results: Region of interest analyses has repeatedly shown gray matter reduction in the superior temporal gyrus of Schizophrenic patients. Conclusion: These results strongly support previous studies regarding brain volume in schizophrenic patients. The connection networks in frontal and temporal lobes evidently did not differ between normal participants and schizophrenia patients.

Objective To examine effects of percutaneous endoscopic debridement and allograft via the transforaminal approach combined with percutaneous pedicle screw fixation as treatment for single-level thoracic tuberculosis. Methods This multicenter retrospective analysis included 75 patients with single-level thoracic tuberculosis who underwent percutaneous endoscopic debridement and allograft via the transforaminal approach combined with percutaneous pedicle screw fixation and were followed for >36 months between January 2012 and December 2014. Results Follow-up was 36–48 months (average 41.1 ± 2.2 months). Intraoperative blood loss was low (average 30.5 ± 7.9 mL), and bed rest time was short (average 1.5 ± 0.3 days). No recurrence was observed in all 75 patients. Except for 3 patients, almost all patients (96%) achieved grade I or II fusion in interbody bone grafting. Segmental Cobb angle was 13.5° ± 4.1° before surgery, 10.5° ± 3.7° immediately after surgery, and 11.7° ± 3.9° at 36 months of follow-up. All patients achieved complete recovery of neurologic function (American Spinal Injury Association grade E), including 15 patients with spinal cord injury (American Spinal Injury Association grade D) before surgery. The visual analog scale and 36-Item Short-Form Health Survey scores significantly improved at 1, 3, 12, and 36 months of follow-up. No complications related to internal fixation occurred within the follow-up period; complication rate was 9.0%. Conclusions Median follow-up clinical experience with percutaneous endoscopic debridement and allograft via the transforaminal approach combined with percutaneous pedicle screw fixation indicates that the technique is safe, effective, feasible, and minimally invasive.

Major depressive disorder (MDD) is a complex mental disorder. The lack of well-established biomarkers hinders its diagnosis, treatment, and new-drug development. N-methyl-D-aspartate receptor (NMDAR) dysfunction has been implicated in the pathogenesis of MDD. This study examined whether expressions of the NMDAR-related genes are characteristic of MDD.Expressions of NMDAR-related genes including SRR, SHMT2, PSAT1, GCAT, GAD1, SLC1A4, NRG1 and COMT in peripheral WBCs of 110 patients with MDD (25 drug-naïve, 21 drug-free, and 64 medicated patients) and 125 healthy individuals were measured using quantitative PCR.The mRNA expression levels of SRR, PSAT1, GCAT, GAD1, NRG1 and COMT were significantly different among the four groups (all p 0.05). For drug-naïve patients, the ΔΔCT values of SRR, PSAT1, GCAT, GAD1, and NRG1 mRNA expressions were significantly different from those in healthy individuals (all p 0.05). The ROC analysis of the ΔΔCT values of the target genes for differentiating drug-naïve patients from healthy controls showed an excellent sensitivity (0.960) and modest specificity (0.640) (AUC = 0.889). Drug-free and medicated patients obtained less favorable AUC values while compared to healthy controls. The results for the age- and sex-matched cohort were similar to those of the unmatched cohort.This is the first study demonstrating that the peripheral mRNA expression levels of NMDAR-related genes may be altered in patients with MDD, especially drug-naïve individuals. The finding supports the NMDAR hypothesis of depression. Whether mRNA expresssion of NMDAR-related genes could serve as a potential biomarker of MDD deserves further investigations.

Objective To evaluate efficacy, safety and feasibility of targeted intracoronary injection using pro-urokinase combined with anisodamine (TCA) versus thrombus aspiration (TA) in ST-elevation myocardial infarction (STEMI) patients with high thrombus loads. Background The best method of avoiding thrombus detachment and stroke in PCI patients with high thrombus loads has not yet been established. Methods STEMI patients receiving coronary artery angiography or percutaneous coronary intervention (CAG/PCI) with thrombus grade ≥ 3 from January 1, 2017 to June 30, 2018 were randomly assigned to targeted intracoronary thrombolysis (pro-urokinase and anisodamine via catheter (TCA) group), or the TA group which followed the standard thrombus aspiration procedure. Parameters compared included thrombus grade, index of microcirculatory resistance (IMR), postoperative myocardial SPECT, thrombosis in myocardial infarction (TIMI) scores including flow grade, corrected TIMI frame counts (CTFCs), and TIMI myocardial perfusion grade (TMPG). Adverse events were followed up within 3 months. Results Thirty-nine patients were finally enrolled. In primary CAG/PCI, the TCA group had higher percentages of TIMI 3 flow and lower IMR values compared with the TA group. The ratio of TMPG 3 grade in the TCA group was higher in repeat CAG, and the perfusion descending area (PDA) presented by SPECT was lower than in the TA group. No significant difference was seen in major adverse coronary events (MACEs) or bleeding events at follow-up. Conclusions TCA appears to be effective, safe, and feasible for repatency and reduction of high thrombus burden in primary PCI and may protect myocardial microcirculation with improved outcomes.

Ginkgolic acids (GAs) and Ginkgotoxin (4'-O-methylpyridoxine, MPN) are main toxic compounds in Ginkgo biloba seeds which are widely used in the treatment of coughing in China. To evaluate the pharmacokinetics of GAs, MPN and their metabolites in rat plasma, a highly sensitive method followed by ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS) has been developed and validated. The proposed method is selective, precise and accurate enough of MPN and its metabolites (4-pyridoxic Acid, pyridoxal, and pyridoxine) for the pharmacokinetic study. After oral administration of MPN, the plasma concentrations of MPN and its metabolites were increased rapidly. Meanwhile, an investigation was carried out to compare the interactions of the pharmacokinetic profiles of MPN and GAs. Five GAs and main metabolites of GA (15:1) and GA (17:1) were also analyzed by using our previous method. After coadministration GAs with MPN, Tmax of MPN delayed and Cmax decreased. Meanwhile, Tmax of 4-pyridoxic Acid, pyridoxal, and pyridoxine were also showed a certain degree of delay. The concentrations of hydroxylation products of GA (15:1) and GA (17:1) increased at a slower rate and the area under the curves was significantly reduced. However, glucuronidation metabolites of GA (15:1) and GA (17:1) were increased faster than administered of GAs alone. The interactions of the pharmacokinetic profiles of GAs and MPN in rat plasma after oral administration were obviously observed.

To evaluate clinical efficacy of modified kidner procedure with tendoscopy in treating painful accessory navicular.From February 2014 to April 2019, 19 patients with painful accessory navicular were admitted, including 13 males and 6 females with a mean age of 26 years old (ranged from 14 to 58 years old), all of which were unilateral symptoms. The courses of disease ranged from 6 to 60 months. All patients received excision of accessory navicular and reconstruction of posterior tibial tendon insertion on navicular with anchor, and the tendoscopy were used to examin the posterior tibial tendon. American Orthopedic Foot and Ankle Society(AOFAS) midfoot score and visual analogue scale(VAS) were used to evaluate efficacy before operation and at the latest follow-up.All the patientswere followed up, and the duration ranged from 12 to 73 months, with an average of (35.0±20.9) months. VAS score was 0.20±0.41 at the latest follow-up, showing significant difference when compared with preoperative score of 6.33±1.95(The modified kidner procedure with tendoscopy is a good choice for the treatment of painful accessory navicular, which could obviously relieve foot pain, improve foot function, and has certain clinical efficacy.

Background: Percutaneous kyphoplasty (PKP) has been reported to provide a favorable analgesic effect for pain caused by osteoporotic vertebral compression fractures (OVCFs). However, a systematic review demonstrated that pain relief was only reported for approximately 86% of kyphoplasty treatments. Objectives: To explore whether an additional facet joint block (FJB) can minimize pain and improve the clinical outcome of PKP in patients with acute OVCFs. Study Design: Prospective study. Setting: All data were from Honghui Hospital in Xi’an. Methods: According to the inclusion and exclusion criteria, 194 patients were eventually included in our study; they were randomly divided into 2 groups of 97 patients each and treated with either PKP + FJB or PKP alone. Follow-up consultations were scheduled 1 day, 3 days, 1 week, 1 month, 3 months, and 1 year postoperatively; the demographic characteristics, related surgical information, and complications observed within both groups were recorded. The clinical evaluation parameters included the intraoperative satisfaction score, the Visual Analog Scale (VAS) score, and the Oswestry Disability Index (ODI). Results: A total of 171 patients (61 men and 110 women; age range: 62–85 years) completed the full postoperative follow-up schedule, with 83 patients in the PKP + FJB group and 88 in the PKP group. No significant differences were observed in the genders, ages, preoperative bone mineral density, surgical levels, or volume of cement injected between the 2 groups (P > 0.05, respectively). The average duration of the surgeries in the PKP + FJB group was slightly longer than that in the PKP group (35.5 ± 4.8 min vs. 31.8 ± 4.3 min; P = 0.038), and in terms of the clinical outcomes, the average intraoperative satisfaction score was significantly higher in the PKP + FJB group (8.6 ± 1.1 vs. 6.3 ± 1.3; P < 0.001). Compared with the preoperative data, significant improvements in the VAS scores of back pain and ODI were observed at each follow-up interval (P < 0.05, respectively). These scores were significantly higher in the PKP + FJB group than in the PKP group; however, this was only observed within the first month after the procedure. Limitations: A single-center noncontrol study. Conclusions: The addition of an FJB (which in our study involved a unique combination of ropivacaine, prednisolone, and vitamin B12) improved the short-term clinical outcome of PKP for acute OVCFs. The local anti-inflammatory and analgesic effects on the facet joints resulted in higher intraoperative satisfaction and lower VAS and ODI scores for the first postoperative month when compared with the PKP group. Key words: Osteoporotic vertebral compression fracture, pain, posterior elements, percutaneous kyphoplasty, facet joint block, medial branch

There has been increasing interest in time-restricted eating to attain intermittent fasting’s metabolic benefits. However, a more extended daily fast poses many challenges. This study was designed to evaluate the effects of a 200-calorie fasting-mimicking diet (FMD) energy bar formulated to prolong ketogenesis and mitigate fasting-associated side effects. A randomized, controlled study was conducted comparing the impact of consuming an FMD bar vs. continued water fast, after a 15-h overnight fast. Subjects in the FMD group showed a 3-h postprandial beta-hydroxybutyrate (BHB) level and 4-h postprandial BHB area under the curve (AUC0–4) that were non-inferior to those who continued with the water fast (p = 0.891 and p = 0.377, respectively). The postprandial glucose AUC0–4 in the FMD group was non-inferior to that in the water fast group (p = 0.899). A breakfast group served as a control, which confirmed that the instrument used in home glucose and ketone monitoring functioned as expected. The results indicate that FMD bar consumption does not interfere with the physiological ketogenesis associated with overnight fasting and could be used to facilitate the practice of time-restricted eating or intermittent fasting.

To investigate the effect of a combined immune score including the lymphocyte-to-monocyte ratio (LMR) and uninvolved immunoglobulin (u-Ig) levels on the prognosis of newly diagnosed multiple myeloma (NDMM) patients treated with bortezomib. Clinical data of 201 NDMM patients were retrospectively analyzed. Patients with LMR ≥ 3.6 and LMR 250 U/L, serum calcium > 2.75 mmol/L, no receipt of regular maintenance treatment, LMR

In this work, the relationships between air quality and pollutant emissions were investigated during the COVID-19 pandemic in Shandong Province. During the quarantine period (from January 24 to February 7, 2020), the concentrations of atmospheric pollutants decreased significantly relative to the period before controls were imposed (from January 15 to 23, 2020). Specifically, except for an increase in the concentration of O

This study aimed to measure the expression of SAA2 in plasma and to assess its diagnostic efficacy as a biomarker for non-small cell lung cancer (NSCLC). The gene expression of SAA2 in NSCLC was analyzed based on a database. Then, SAA2 expression was detected by immunohistochemistry in lung tissue and by enzyme-linked immunosorbent assay in 90 patients with NSCLC and 61 normal controls. Finally, the diagnostic performance was assessed in terms of accuracy, sensitivity, and specificity. At the gene and protein levels, the SAA2 expression was significantly higher in the NSCLC group than in the control group (p < 0.01). It was higher in lung squamous carcinoma than in lung adenocarcinoma and in males than in females, and this trend was also observed in the lung squamous carcinoma group. Of note, the expression of SAA2 increased with increasing disease stage. Receiver operating characteristic (ROC) curve analysis revealed that the sensitivity of SAA2 was 83.61%, the specificity was 91.11%, and the area under the curve (AUC) was 0.9252. Its accuracy was 68.89%, which was higher than that of other conventional diagnostic biomarkers, and the combined application can effectively improve the diagnostic efficiency. Based on the results, SAA2 expression was positively correlated with the disease stage of NSCLC. Notably, SAA2 is more concerning in male patients with lung squamous carcinoma, and it can help in the screening and diagnosis of NSCLC. SAA2 may represent a novel diagnostic biomarker in NSCLC.

OBJECTIVE: To assess the mid-term effectiveness of anterior cruciate ligament (ACL) revision and to analyze the relevant factors that may affect the surgical outcomes. METHODS: The clinical data of 24 patients who underwent ACL revision surgery between April 2009 and July 2018 and were followed up for more than 2 years were retrospectively analyzed. There were 20 males and 4 females with a median age of 30 years [interquartile distance (IQR) was (25, 36) years]. The median body mass index was 24.45 kg/m(2) and IQR was (22.93, 25.93) kg/m(2). The median time between ACL revision and reconstruction was 41 months and IQR was (15, 85) months. The direct cause of the failure of reconstruction surgery included 14 cases of trauma, 8 cases of no obvious cause, and 2 cases of infection. During the revision operation, 14 patients had a poor bone tunnel position, all of which were drilled with new tunnels, the remaining 10 patients were freshly modified on the basis of the original bone tunnel. Seventeen patients used autogenous tendon revision, 7 patients used LARS ligament; 16 patients had cartilage injury. The Lysholm score, the International Knee Documentation Committee (IKDC) score, and the Tegner sports rating score were used for functional evaluation before operation, at 1 year after operation, and at last follow-up. The Likert satisfaction score was recorded at last follow-up. RESULTS: Patients were followed up with a median time of 47 months and IQR was (32, 61) months. The Lysholm score, IKDC score, and Tegner sports rating score were significantly improved at 1 year after operation and at last follow-up when compared with preoperative scores (P0.05). At last follow-up, the median Likert satisfaction score was 4.0 and IQR was (3.0, 4.5). According to the presence or absence of cartilage damage and the type of graft, the above scores at last follow-up were compared between the groups, and the differences were not significant (P>0.05). At last follow-up, 2 patients had graft fractures due to trauma again, and autogenous iliac bones were taken to fill the bone tunnel, and the second stage was revised; the rest of the patients recovered satisfactorily. CONCLUSION: With preoperative identification of the cause of ACL reconstruction failure, the stability and function of knee joint can be significantly improved by selecting appropriate bone tunnels and grafts during the revision and by active rehabilitation exercises.

Background According to recent evidence, psychobiotics exert beneficial effects on central nervous system-related diseases, such as mental disorders. Lactobacillus plantarum PS128 (PS128), a novel psychobiotic strain, improves motor function, depression, and anxiety behaviors. However, the psychobiotic effects and mechanisms of PS128 in Alzheimer’s disease (AD) remain to be explored. Objectives The goal of the current study was to evaluate the beneficial effects of PS128 and to further elucidate its mechanism in AD mice. Methods PS128 (1010 colony-forming unit (CFU)/ml) was administered via oral gavage (o.g.) to 6-month-old male wild-type B6 and 3 × Tg-AD mice (harboring the PS1M146V, APPswe and TauP30IL transgenes) that received an intracerebroventricular injection of streptozotocin (icv-STZ, 3 mg/kg) or vehicle (saline) for 33 days. After serial behavioral tests, fecal short-chain fatty acid levels and AD-related pathology were assessed in these mice. Results Our findings show that intracerebroventricular injection of streptozotocin accelerated cognitive dysfunction associated with increasing levels of glycogen synthase kinase 3 beta (GSK3β) activity, tau protein phosphorylation at the T231 site (pT231), amyloid-β (Aβ) deposition, amyloid-β protein precursor (AβPP), β-site AβPP-cleaving enzyme (BACE1), gliosis, fecal propionic acid (PPA) levels and cognition-related neuronal loss and decreasing postsynaptic density protein 95 (PSD95) levels in 3 × Tg-AD mice. PS128 supplementation effectively prevented the damage induced by intracerebroventricular injection of streptozotocin in 3 × Tg-AD mice. Conclusions Based on the experimental results, intracerebroventricular injection of streptozotocin accelerates the progression of AD in the 3 × Tg-AD mice, primarily by increasing the levels of gliosis, which were mediated by the propionic acid and glycogen synthase kinase 3 beta pathways. PS128 supplementation prevents damage induced by intracerebroventricular injection of streptozotocin by regulating the propionic acid levels, glycogen synthase kinase 3 beta activity, and gliosis in 3 × Tg-AD mice. Therefore, we suggest that PS128 supplementation is a potential strategy to prevent and/or delay the progression of AD.

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers due to its high metastasis rate in the liver. However, little is known about the molecular features of hepatic metastases due to difficulty in obtaining fresh tissues and low tumor cellularity. Results We conduct exome sequencing and RNA sequencing for synchronous surgically resected primary tumors and the paired hepatic metastases from 17 hepatic oligometastatic pancreatic ductal adenocarcinoma and validate our findings in specimens from 35 of such cases. The comprehensive analysis of somatic mutations, copy number alterations, and gene expressions show high similarity between primary tumors and hepatic metastases. However, hepatic metastases also show unique characteristics, such as a higher degree of 3p21.1 loss, stronger abilities of proliferation, downregulation of epithelial to mesenchymal transition activity, and metabolic rewiring. More interesting, altered tumor microenvironments are observed in hepatic metastases, especially a higher proportion of tumor infiltrating M2 macrophage and upregulation of complement cascade. Further experiments demonstrate that expression of C1q increases in primary tumors and hepatic metastases, C1q is mainly produced by M2 macrophage, and C1q promotes migration and invasion of PDAC cells. Conclusion Taken together, we find potential factors that contribute to different stages of PDAC metastasis. Our study broadens the understanding of molecular mechanisms driving PDAC metastasis.

To analyze the outcomes and adverse events of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiation with modified radiotherapy volume and increased radiation dose. This was a retrospective analysis of patients with ESCC treated with definitive chemoradiotherapy at the Sun Yat-sen University Cancer Center (02/2015 to 02/2017). The dose to the planning gross tumor volume (PGTV) and planning clinical tumor volume (PTV1) was 66-68 Gy (2.0-2.2 Gy/fraction). The dose to the planning regional lymph node drainage area volume (PTV2) was 46 Gy (2.0 Gy/fraction). Treatment response, adverse events, progression-free survival (PFS), overall survival (OS), and locoregional failure-free survival (LRFFS) were analyzed. Twenty-six patients were included. The median follow-up was 31 (range, 4.3-51.3) months. Sixteen (61.5%) patients had a complete response, and four (15.4%) achieved a partial response. The objective response rate was 76.9%, and the disease control rate was 80.8%. The median PFS and OS were not achieved. The 4-year PFS was 63.9%, and the 4-year OS was 71.0%. Grade 1-2 and 3-4 radiation-related esophagitis was observed in 15 (57.7%) and one (4.5%) patients, respectively. Grade 1-2 and 3-4 radiation-related pneumonitis was observed in 12 (46.2%) and one (4.5%) patients, respectively. No patients developed radiation-related heart or skin damage. The modified target volume definition and increased dose of definitive radiotherapy combined with chemotherapy in patients with ESCC had low toxicity and might improve survival, but additional trials are necessary to prove the superiority of this strategy.

Bone loss is one of the most serious medical problem associated with prolonged weightlessness in long-term spaceflight mission. Skeletal reloading after prolonged spaceflight have indicated incomplete recovery of lost bone, which may lead to an increased risk of fractures in astronauts when returning to Earth. Substantial studies have revealed the capacity of static magnetic fields (SMFs) on treating various bone disorders, whereas it is unknown whether SMFs have the potential regulatory effects on bone quality in unloaded mice during unloading. This study was conducted to investigate the potential effects of whole-body SMF exposure with 0.2–0.4 T on the recovery of unloading-induced bone loss. Eight‐week‐old male C57BL/6J mice were subjected to hindlimb unloading (HLU) for 4 weeks, following the mice were reloaded for 4 weeks under geomagnetic field (GMF) and SMF of 0.2–0.4 T. Bone quality indexes, including bone mineral density (BMD) and bone mineral content (BMC), bone microarchitecture, and bone mechanical properties were examined by the measurement of dual energy X-ray absorptiometry (DEXA), micro-computed tomography (Micro-CT), and 3-point bending. Bone turnover was evaluated by bone histomorphometric and serum biochemical assay. We found that SMF exposure for 4 weeks significantly promoted the recovery in HLU-induced decrease of BMD and BMC, deterioration of bone microarchitecture, and reduction of bone strength. The results from bone turnover determination revealed that SMF exposure for 4 weeks induced lower osteoclast number of trabecular bone and serum TRAP-5b levels in reloaded mice, whereas SMF showed no significant alteration in skeletal osteoblast number and serum osteocalcin levels. Together, our findings suggest that SMF of 0.2–0.4 T facilitated the recovery of unloading-induced bone loss by inhibiting the increase of bone resorption in reloaded mice, and indicate that SMF might become a promising biophysical countermeasure for maintaining bone health in astronauts after landing.

Second primary cancer is prevalent in patients with gastrointestinal (GI) cancer, for which lung cancer is the most common and associated with high lethality. Image screening for lung cancer was proved to be effective in early diagnosis and lower mortality. However, trials of screen for lung cancer generally excluded patients with a previous diagnosis of malignancy. The study aimed to investigate the outcome of second primary lung cancer and the factor that improve survival in patients with hepato-GI cancer. A total of 276 patients with secondary lung cancer were found among 3723 newly-diagnosed lung cancer patients diagnosed in Chang Gung Memorial Hospital, between 2010 and 2014. Patients’ clinical characteristics, stages and survival were recorded and analyzed. The patients were separated into 2 groups: Group I was defined as lung cancer detected in original primary cancer clinic and group II patients defined as lung cancer detected in other medical places. Sixty-nine cases with primary GI-hepatic and secondary lung cancer were diagnosed (42 (60.8%) in Group I and 27 (39.1%) in Group II). Although both groups had comparable primary cancer stages and treatment, more patients in Group I than Group II were diagnosed as early stage lung cancer (stage I-II: 40.5% vs 11.1%; P = .023). Group II had larger lung tumor sizes than Group I (4.7 vs 3.5 cm; P = .025). Group I showed better 5-year overall survival than Group II (P = .014, median survival: 27 vs 10 months). Among Group II, only 37% had received image follow up in clinic compared with 67% of Group I cases (P = .025). Patients with chest image follow up in clinics also had better 5-year overall survival (P = .043). GI-hepatic cancer was the most common primary malignancy in the lung cancer cohort. Patients had better survival outcome when secondary lung cancer was diagnosed in original primary cancer clinic. Chest image screening strategy may contribute better survival in secondary lung cancer due to detection at an earlier stage.

Objectives Non-invasive brain stimulation (NIBS) is beneficial to many neurological and psychiatric disorders by modulating neuroplasticity and cortical excitability. However, recent studies evidence that single type of NIBS such as transcranial direct current stimulation (tDCS) does not have meaningful clinical therapeutic responses due to their small effect size. Transcranial near-infrared stimulation (tNIRS) is a novel form of NIBS. Both tNIRS and tDCS implement its therapeutic effects by modulating cortical excitability but with different mechanisms. We hypothesized that simultaneous tNIRS and tDCS is superior to single stimulation, leading to a greater cortical excitability. Methods Sixteen healthy subjects participated in a double-blind, sham-controlled, cross-over designed study. Motor evoked potentials (MEPs) were used to measure motor cortex excitability. The changes of MEP were calculated and compared in the sham condition, tDCS stimulation condition, tNIRS condition and the simultaneous tNIRS and anodal tDCS condition. Results tDCS alone and tNIRS alone both elicited higher MEP after stimulation, while the MEP amplitude in the simultaneous tNIRS and tDCS condition was significantly higher than either tNIRS alone or tDCS alone. The enhancement lasted up to at least 30 minutes after stimulation, indicating simultaneous 820 nm tNIRS with 2 mA anodal tDCS have a synergistic effect on cortical plasticity. Conclusions Simultaneous application of tNIRS with tDCS produces a stronger cortical excitability effect. Significance The simultaneous tNIRS and tDCS is a promising technology with exciting potential as a means of treatment, neuro-enhancement, or neuro-protection.

The Global Leadership Initiative on Malnutrition (GLIM) is new criteria for diagnosing malnutrition that need validation adjusted to race. Our aim is to determine the optimal reference values of calf circumference (CC), investigate the prevalence of GLIM-defined malnutrition based on different screening tools in inpatients over 70 years old in China and assess its relationship with clinical outcomes. We designed two continuity studies by analyzing a prospective multicenter database. First, we estimated and validated the CC cut-off values by receiver operating characteristic analyses against in-hospital mortality. Then the patients who were at risk by NRS 2002, MNA-SF and MUST were assessed by the GLIM criteria using the new CC values. Some clinical parameters and outcome data were evaluated. The optimal cut-off values of CC were 29.6 cm for male patients and 27.5 cm for female patients. The prevalence of GLIM-defined malnutrition was 27.5% by using NRS2002, 32.6% by using MNA-SF and 25.4% by using MUST. Patients with GLIM-defined malnutrition showed significantly worse values in BMI, total protein, albumin, neutrophil/lymphocyte ratio, CC, rate of complication, in-hospital mortality, length of stay, and total hospital cost than normal patients. Multivariate logistic regression showed the odds ratio of in-hospital mortality was significantly associated with GLIM defined malnutrition by using MNA-SF [OR = 1.231, 95%CI (1.022, 1.484), P = 0.029]. The Chinese reference values of CC for inpatients over 70 years old were validated by in-hospital mortality, which could be implemented in GLIM criteria. And this population possessed a high prevalence of nutrition risk and malnutrition. GLIM criteria with MNA-SF seems to be the first choice to diagnose malnutrition.

Hyperphosphorylated and truncated tau variants are enriched in neuropathological aggregates in diseases known as tauopathies. However, whether the interaction of these posttranslational modifications affects tau toxicity as a whole remains unresolved. By expressing human tau with disease-related Ser/Thr residues to simulate hyperphosphorylation, we show that despite severe neurodegeneration in full-length tau, with the truncation at Asp421, the toxicity is ameliorated. Cytological and biochemical analyses reveal that hyperphosphorylated full-length tau distributes in the soma, the axon, and the axonal terminal without evident distinction, whereas the Asp421-truncated version is mostly restricted from the axonal terminal. This discrepancy is correlated with the fact that fly expressing hyperphosphorylated full-length tau, but not Asp421-cleaved one, develops axonopathy lesions, including axonal spheroids and aberrant actin accumulations. The reduced presence of hyperphosphorylated tau in the axonal terminal is corroborated with the observation that flies expressing Asp421-truncated variants showed less motor deficit, suggesting synaptic function is preserved. The Asp421 cleavage of tau is a proteolytic product commonly found in the neurofibrillary tangles. Our finding suggests the coordination of different posttranslational modifications on tau may have an unexpected impact on the protein subcellular localization and cytotoxicity, which may be valuable when considering tau for therapeutic purposes.

Background: Local anesthesia (LA) is widely used in knee arthroscopic surgery but not in ankle arthroscopy. Objective: To understand the effectiveness and safety of LA combined with ropivacaine in pain control for ankle arthroscopy. Study Design: Retrospective cohort. Methods: We retrospectively collected data for patients who underwent ankle arthroscopy from April 2012 to April 2017. Patients were grouped by anesthesia method: LA, LA with ropivacaine (LA+R), spinal anesthesia (SA), and SA with ropivacaine (SA+R). Intra- and postoperative visual analog scale (VAS) scores, complications, doses of supplemental pain medication, hospitalization cost and duration, and satisfaction with pain control during hospitalization were analyzed. Results: The study included 276 patients (LA: 93; LA+R: 124; SA: 31; SA+R: 28). The LA and LA+R groups had significantly higher intraoperative VAS scores (LA vs. SA, p = 0.001; LA vs. SA+R, p = 0.002; LA+R vs. SA, p = 0.00; LA+R vs. SA+R, p = 0.00), but fewer complications, than the SA and SA+R groups. The LA+R and SA+R groups had significantly better outcomes for postoperative pain control (LA vs. LA+R, p = 0.01; LA vs. SA+R, p = 0.01; SA vs. SA+R, p = 0.01; SA vs. LA+R, p = 0.03) and required less supplemental pain medication. Hospitalization cost was lower and duration shorter in the LA and LA+R groups than in the SA and SA+R groups. There was no significant difference in satisfaction among the four groups. Limitations: This was a single-center retrospective and relatively short-term study. Conclusions: LA+R which could be safely applied in ankle arthroscopy provided satisfactory pain control, reduced postoperative pain intensity, fewer complications, shorter hospital stay, and good cost-effectiveness. It can be safely applied in ankle arthroscopy for the specific patients with ankle osteoarthritis.

As a typical industrial city, Linyi has suffered severe atmospheric pollution in recent years. Meanwhile, a high incidence of respiratory and circulatory diseases has been observed in Linyi. The relationship between air pollutants and the prevalence of respiratory and circulatory system diseases in Linyi is still unclear, and therefore, there is an urgent need to assess the human health risks associated with air pollutants. In this study, the number of outpatient visits and spatial distribution of respiratory and circulatory diseases were first investigated. To clarify the correlation between diseases and air pollutant emissions, the residential intake fraction (IF) of air pollutants was calculated. The results showed that circulatory and respiratory diseases accounted for 62.32% of the total causes of death in 2015. The incidence of respiratory diseases was high in the winter, and outpatient visits were observed for more males (60.9%) than females (39.1%). The spatial distribution suggested that outpatient visits for respiratory and circulatory diseases were concentrated in the main urban area of Linyi, including the Hedong District, Lanshan District, and Luozhuang District, and especially at the junction of these three areas. After calculating the IF combined with the characteristics of pollution sources, meteorological conditions, and population data, a high IF value was concentrated in urban and suburban areas, which was consistent with the high incidence of diseases. Moreover, high R values and a significant correlation (R > 0.6, p

Background During the process of shearing the ligamentum flavum, rotating the working channel, and manipulating the annulus fibrosis, the sinuvertebral nerve and the spinal nerve root can be irritated, inducing intolerable back and leg pain. Thus, general anesthesia is recommended and well accepted by most surgeons when performing percutaneous endoscopic lumbar discectomy (PELD) via the interlaminar approach. The aim of our study was to explore the efficacy and safety of percutaneous endoscopy interlaminar lumbar discectomy with gradient local anesthesia (LA) in patients with L5/S1 disc herniation. Methods This retrospective study was conducted between December 2017 and June 2018. The study included 50 consecutive patients who met the study criteria, had single-level L5/S1 disc herniation, and underwent PELD via the interlaminar approach under gradient LA. Different concentrations of local anesthetic compound (LAC) were injected into different tissues inside and outside the ligamentum flavum to complete gradient LA. The evaluation criteria included the intraoperative satisfaction score, visual analog scale (VAS) score, Oswestry Disability Index (ODI), complications, and adverse reactions. Results The intraoperative satisfaction score was consistently over 7, with an average score of 9.3 ± 0.7, indicating that LAC can achieve satisfactory pain control throughout the PELD operation without additional anesthesia. The postoperative VAS score and ODI were dramatically improved at each follow-up interval (P < 0.001, respectively). There was no serious complication such as dural rupture caused by puncture, dural laceration caused by manipulation under endoscopy, total spinal anesthesia, iatrogenic nerve root injury, epidural hematoma, infections, or local anesthetic-related adverse reactions. Three patients experienced transient postoperative dysesthesia of the lower limbs that gradually recovered within 24 h. Conclusions Gradient local anesthesia can satisfactorily and safely control intraoperative pain during the PELD via the interlaminar approach. It can not only improve intraoperative satisfaction, but also reduce local anesthesia-related adverse reactions and surgery-related complications.

Nontuberculous mycobacteria (NTM) disease is of increasing public health concern; however, data regarding pleural effusion in NTM disease patients are limited. The purpose of this study was to investigate the clinical relevance and characteristics of NTM pleuritis. Patients with pleural effusion and NTM disease diagnosed between April 2012 and November 2017 were enrolled and their medical records were retrospectively reviewed. Clinical characteristics and treatment outcomes were analyzed. A total of seven among 100 patients with NTM disease had NTM pleuritis (7%). Flow cytometry of T and B lymphocytes revealed varying degrees of cellular immunodeficiency in five cases (71.4%). NTM pleuritis with pneumothorax occurred in five patients (71.4%) and bronchopleural fistula (BPF) was also found in four of them. All seven patients had delayed diagnosis and the mean time of diagnosis was 7 months (1-24 months). Four patients successfully completed treatment, while three patients (42.8%) succumbed to progressing NTM disease. Low CD4-positive T-cell counts were common in NTM pleuritis patients. Delayed diagnosis and treatment resulted in increased incidence of NTM pleurisy and poor prognosis. Moreover, BPF is perhaps a characteristic feature of Mycobacterium avium complex-associated pleuritis.

Background: The tumor microenvironment (TME) consists of heterogeneous cell populations, including malignant cells and nonmalignant cells that support tumor proliferation, invasion, and metastasis through extensive cross talk. The intra-tumor immune landscape is a critical factor influencing patient survival and response to immunotherapy. Methods: Gene expression data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Immune cell infiltration was determined by single-sample Gene Set Enrichment Analysis (ssGSEA) depending on the integrated immune gene sets from published studies. Univariate analysis was used to determine the prognostic value of the infiltrated immune cells. Least absolute shrinkage and selection operator (LASSO) regression was performed to screen for the most survival-relevant immune cells. An immune-cell characteristic score (ICCS) model was constructed by using multivariate Cox regression analysis. Results: The immune cell infiltration patterns across 32 cancer types were identified, and patients in the high immune cell infiltration cluster had worse overall survival (OS) but better progression-free interval (PFI) compared to the low immune cell infiltration cluster. However, immune cell infiltration showed inconsistent prognostic value depending on the cancer type. High immune cell infiltration (High CI) indicated a worse prognosis in brain lower grade glioma (LGG), glioblastoma multiforme (GBM), and uveal melanoma (UVM), and favorable prognosis in adrenocortical carcinoma (ACC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), cholangiocarcinoma (CHOL), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), sarcoma (SARC), and skin cutaneous melanoma (SKCM). LUAD prognosis was significantly influenced by the infiltration of 13 immune cell types, with high infiltration of all but Type 2 T helper (Th2) cells correlating with a favorable prognosis. The ICCS model based on six most survival-relevant immune cell populations was generated that classified patients into low- and high-ICCS groups with good and poor prognoses, respectively. The multivariate and stratified analyses further revealed that the ICCS was an independent prognostic factor for LUAD. Conclusions: The infiltration of immune cells in 32 cancer types was quantified, and considerable heterogeneity was observed in the prognostic relevance of these cells in different cancer types. An ICCS model was constructed for LUAD with competent prognostic performance, which can further deepen our understanding of the TME of LUAD and can have implications for immunotherapy.

Previous studies suggest that COVID-19 is more likely to infect older adult men, particularly those with chronic comorbidities 2-4 Few infections in children have been reported We identified all infected infants in China and described demographic, epidemiologic, and clinical features