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Dan Ye,1 Ding Ding,1 Ling-Yun Pan,2 Qing Zhao,3 Long Chen,2 Min Zheng,1 Tong Zhang,1 Bing-Liang Ma1 1Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Department of Pharmacy, Jing’an District Zhabei Central Hospital, Shanghai, 200070, People’s Republic of ChinaCorrespondence: Bing-Liang Ma; Tong Zhang, Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, No. 1200 Cai Lun Road, Pudong New District, Shanghai, 201203, People’s Republic of China, Tel +86-021-5132 2199 ; +86-021-5132 2318, Fax +86-021-5132 2192, Email bingliang.ma@hotmail.com; zhangtongshutcm@hotmail.comPurpose: Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract.Methods: DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX’s shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines.Results: Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of − 20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells.Conclusion: The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines. Keywords: docetaxel, oral delivery, self-assembly, nanoparticles, pharmacokinetics, coptidis rhizoma

Shuzhong Liu,1,* Xi Zhou,1,* An Song,2 Zhen Huo,3 Siyuan Yao,1 Yipeng Wang,1 Yong Liu,1,* Ling-Ya Pan4,* 1Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Endocrinology, Key Laboratory of Endocrinology, National Health and Family Planning Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong LiuDepartment of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan Wangfujing, Beijing 100730, People’s Republic of China, Email liuyong_pumch@163.comLing-Ya PanDepartment of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, People’s Republic of ChinaEmail panly@pumch.cnObjective: The purpose of this study is to provide key information on the clinical characteristics, surgical treatment, and potential prognostic factors in patients with metastatic spinal gynecologic cancer (MSGC), with a view to their application in clinical practice.Methods: From January 2010 to January 2020, we performed a retrospective analysis of 14 patients with MSGC who underwent surgical treatment in a single center. Surgical treatment was performed on 14 patients, and a total of 14 operations were performed. The survival time of patients after spinal surgery was analyzed by Kaplan–Meier and Cox regression analysis.Results: The average age of patients was 51.9 years (range 25‒70). The average time from initial surgery to the discovery of spinal metastasis was 60.3 months (2‒180), and the average follow-up time was 19.2 months (2‒55). Spinal tumor progression was found in 9 patients, and 12 patients (85.7%) died during follow-up. In univariate analysis, extraosseous visceral metastasis (p = 0.024), revised Tokuhashi stage (p = 0.025), Tomita stage (p = 0.005), and number of spinal lesions (p = 0.038) were associated with overall survival (OS). Extraosseous visceral metastasis (p = 0.026), revised Tokuhashi stage (p = 0.014), Tomita stage (p = 0.001), and gynecological cancer type (p = 0.039) were associated with progression-free survival.Conclusion: Surgical treatment is an effective treatment for MSGC and relieves pain, restores function and rebuilds stability. Based on our single-center experience, extraosseous visceral metastasis, revised Tokuhashi stage, Tomita stage, and gynecological cancer type may be potential prognostic factors for OS.Keywords: clinical prognosis, gynecological cancer, overall survival, progression-free survival, spinal metastasis, surgical treatment

Yan-Yan Zhang, Yan Li, Meng Qin, Yan Cai, Ying Jin, Ling-Ya Pan Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China Objectives: The aim of this study was to evaluate the factors associated with progress-free survival (PFS) and overall survival (OS) in patients with high-grade endometrial stromal sarcoma (HG-ESS). Patients and methods: A total of 40 patients were enrolled in this study at the Peking Union Medical College Hospital, Beijing, China, from 2006 to 2016. The study retrospectively analyzed clinical and pathological data, and associations of these variables with PFS and OS were evaluated. Results: The age of the patients at the time of diagnosis ranged from 16 to 73 years. Abnormal vaginal bleeding was the most commonly observed symptom. The tumor size ranged from 2 to 19 cm. The tumor locations were as follows: vulva (1 case), ovary (2 cases), broad ligament (2 cases), cervix (7 cases), and uterus (28 cases). A total of 34 (85%) and 6 (15%) patients underwent complete and ovarian preservation surgery, respectively. Notably, 33 (82.5%), 13 (32.5%), and 5 (12.5%) patients received adjuvant chemotherapy, radiation therapy, and hormone treatment, respectively. Lymph node dissection was performed in 15 (37.5%) patients (positive rate: 7.4%), 16 (40%) patients underwent omentectomy (positive rate: 10%), and 12 (30%) patients underwent peritoneal lavage cytology (positive rate: 0%). Eighteen (45%) patients had lymphovascular space invasion, 13 (32.5%) patients had uterine fibroids, and 11 (27.5%) patients were diagnosed with endometriosis. Moreover, the levels of CA125 in the serum were measured prior to and following treatment. The median PFS and OS were 9 and 24 months, respectively. Eventually, 29 (72.5%) patients experienced relapse and 19 (47.5%) patients expired due to the disease. Conclusion: Patients with advanced HG-ESS (stage II–IV) were associated with poor prognosis. The minimum value of CA125 and endometriosis were independent risk factors for PFS. The stage of disease, size of the tumor, minimum and average values of CA125, menopause, history of uterine leiomyoma, and endometriosis were independent risk factors for OS. The combination of surgery with radiotherapy and chemotherapy may improve the PFS of patients in the early stage of the disease. Keywords: high-grade endometrial stromal sarcoma, CA125, treatment, prognosis

LingYu Pan,1,* YanQuan Han,1,* YongZhong Wang,1 QianQian Chen,2 Ying Wu,2 Yuan Sun2 1Grade 3 Preparation Laboratory of State Administration of TCM, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China; 2Anhui University of Chinese Medicine, Hefei, Anhui 230031, China *These authors contributed equally to this work Purpose: Yanghe Pingchuan granules (YPG), a hospital preparation developed by The First Affiliated Hospital, Anhui University of Chinese Medicine, has been used for the clinical treatment of bronchial asthma (BA) for several decades. This study aimed to explore the mechanism of action of YPG in the treatment of BA. Materials and methods: Male Sprague Dawley rats (n=60) were randomly divided into six groups (n=10 per group): control, a BA model, positive drug control (Guilong Kechuanning capsules; a proven effective treatment for BA), and model rats treated with a high, medium, or low dose of YPG. H&E staining was used to detect pathological changes in the bronchial tubes. The mRNA expression levels of PI3K, PKB, PCNA, and AR were determined by real-time PCR, and the protein levels of phospho- (p-)PI3K, p-PKB, p-PCNA, and p-AR were detected by Western blotting. ELISAs were used to detect the expression of PIP2, PIP3 IL-6, IL-8, IL-1β, and epinephrine (EPI). Results: H&E staining demonstrated that BA can be ameliorated using YPG. Real-time PCR, Western blotting, and ELISA indicated that use of YPG decreased expression of the phosphoinositide 3-kinase (PI3K) signaling pathway and PCNA, and can also ameliorate the condition kidney Yang deficiency, which is associated with BA in Chinese traditional medicine. Conclusion: YPG can attenuate BA therapeutically in a dose-dependent manner. The mechanism underlying its therapeutic effect comprises influences on three features that contribute to BA: the PI3K signaling pathway, cell proliferation, and “kidney-Yang deficiency”. Keywords: bronchial asthma, YPG, PI3K/PKB signaling pathway, cell proliferation, kidney Yang deficiency

The stability of a predator-prey model with two-stage structure and fear effect was studied. This model incorporated maturation time delay of the prey, and a delay differential equation model was established. By using the theory of the ordinary differential equations, the comparison theorem, the theory of the delay differential equations and the persistence theory of the infinite dimensional dynamical systems, the nonnegativity and boundedness of the solution of the model were proved, the conditions for the existence of the equilibria were given, the local asymptotic stability and the global asymptotic stability of the equilibria and the uniform persistence of the model were discussed. Numerical simulation was used to verify the correctness of the theoretical results, and it is concluded that the stability of the model changes when the fear effect and time delay are different.

Given the transmission of hand-foot-mouth disease (HFMD) is related to the age structure of the host, an age-structured model for the disease transmission dynamics of HFMD is formulated and analyzed. The positivity of the model is obtained by using the semigroup method, and then the basic reproduction number of the model is given, by the linearization method and Fatou lemma. It is proved that the disease-free equilibrium is globally asymptotically stable if R01. The local stability conditions for the disease-endemic steady state is also given, and the disease exists.

We identified two gall-inducing wasp species infesting eucalypts leaves, including an undescribed species, Ophelimus cracens sp. nov., and Epichrysocharis burwelli , which is a new record for Taiwan. The major hosts of O. cracens were Eucalyptus grandis , Eu. urophylla , and Eu. camaldulensis (Myrtaceae) . We observed failed galls of O. cracens at an early stage on Eu. amplifolia and Corymbia maculata . All O. cracens adults discovered on infected leaves were females, and four parasitoid species were identified in samples collected from two cities, three counties, and four municipalities across Taiwan. Epichrysocharis burwelli was exclusively found on C. citriodora in Hsinchu, Nantou, and Tainan Cities. This marks the first record of Ep. burwelli in Asia, accompanied by the identification of one parasitoid species. The adult longevity of adults which emerged from their major hosts, when provided with honey-water solution, was 5.5 days for O. cracens and 5.7 days for Ep. burwelli . Recognizing the potential damage by these wasps on Eucalyptus production areas in the absence of parasitoids, further investigations of their biology and control are warranted.

Background and Aim: Currently, hepatitis B virus-related acute liver failure (HBV-ALF) has limited treatment options. Studies have shown that histone lactylation plays a role in the progression of liver-related diseases. Therefore, it is essential to explore lactylation-related gene (LRGs) biomarkers in HBV-ALF to provide new information for the treatment of HBV-ALF., Methods: Two HBV-ALF-related datasets (GSE38941 and GSE14668) and 65 LRGs were used. First, the differentially expressed genes (DEGs) were derived from differential expression analysis, the key module genes from weighted gene co-expression network analysis; and LRGs were used to intersect to obtain the candidate genes. Subsequently, the feature genes obtained from least absolute shrinkage and selection operator regression analysis and support vector machine analysis were intersected to obtain the candidate key genes. Among them, genes with consistent and significant expression trends in both GSE38941 and GSE14668 were used as biomarkers. Subsequently, biomarkers were analyzed for functional enrichment, immune infiltration, and sensitive drug prediction., Results: In this study, five candidate genes (PIGM, PIGA, EGR1, PIGK, and PIGL) were identified by intersecting 6461 DEGs and 2496 key module genes with 65 LRGs. We then screened four candidate key genes from the machine learning algorithm, among which PIGM and PIGA were considered biomarkers in HBV-ALF. Moreover, the results of enrichment analysis showed that the significant enrichment signaling pathways for biomarkers included allograft rejection and valine, leucine, and isoleucine degradation. Thereafter, 11 immune cells differed significantly between groups, with resting memory CD4+ T cells having the strongest positive correlation with biomarkers. Methylphenidate hydrochloride is a potential therapeutic drug for PIGM., Conclusion: Two genes, PIGM and PIGA, were identified as biomarkers related to LRGs in HBV-ALF, providing a basis for understanding HBV-ALF pathogenesis., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

We employed first-principles calculations to investigate the effect of chemical doping on the lithiation kinetics and dynamic properties of the c-Si anode. Our ab initio molecular dynamics simulations reveal that phosphorous/arsenic doping can greatly enhance the lithiation kinetics of c-Si, whereas boron doping is unable to produce such an improvement. Our calculations also show that boron doping could enhance Li insertion into c-Si, but phosphorous/arsenic doping tends to increase the insertion energy of Li ions. Although the migration energy barriers of Li ions may slightly increase (decrease) in the boron-(phosphorus-/arsenic-)doped c-Si, these changes were only effective within the range of the nearest-neighbor distance from dopants. Furthermore, it was found that the phosphorus-/arsenic-doped Si can be more ductile and can more easily undergo plastic deformation upon lithiation, while the c-Si matrix becomes more brittle and stiffer when doped with boron. Our simulation results also demonstrate that phosphorous- and arsenic-doping can effectively speed up the Li-induced structural amorphization of c-Si while boron doping appears to severely slow it down. These findings unambiguously indicate that the induced mechanical softening of the c-Si bond network can be the primary factor that leads to the enhanced lithiation kinetics in the n-type doped c-Si anodes., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ 2 =1.296, P =0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ 2 =0.001, P =0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ 2 =0.113, P =0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference ( χ 2 =0.080, P =0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences ( P =0.287, P =0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P =0.138) and 5-year OS rate (36.1% vs 38.8%; P =0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia. The ratio of red cell distribution width (RDW) to albumin has been recognized as a reliable prognostic marker for poor outcomes in a variety of diseases. However, the evidence regarding the association between RDW to albumin ratio (RAR) and in hospital mortality in patients with AF admitted to the Intensive Care Unit (ICU) currently was unclear. The purpose of this study was to explore the association between RAR and in hospital mortality in patients with AF in the ICU., Methods: This retrospective cohort study used data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database for the identification of patients with atrial fibrillation (AF). The primary endpoint investigated was in-hospital mortality. Multivariable-adjusted Cox regression analysis and forest plots were utilized to evaluate the correlation between the RAR and in-hospital mortality among patients with AF admitted to ICU. Additionally, receiver operating characteristic (ROC) curves were conducted to assess and compare the predictive efficacy of RDW and the RAR., Results: Our study included 4,584 patients with AF with a mean age of 75.1 ± 12.3 years, 57% of whom were male. The in-hospital mortality was 20.3%. The relationship between RAR and in-hospital mortality was linear. The Cox proportional hazard model, adjusted for potential confounders, found a high RAR independently associated with in hospital mortality. For each increase of 1 unit in RAR, there is a 12% rise in the in-hospital mortality rate (95% CI 1.06-1.19). The ROC curves revealed that the discriminatory ability of the RAR was better than that of RDW. The area under the ROC curves (AUCs) for RAR and RDW were 0.651 (95%CI: 0.631-0.671) and 0.599 (95% CI: 0.579-0.620)., Conclusions: RAR is independently correlated with in hospital mortality and in AF. High level of RAR is associated with increased in-hospital mortality rates., (© 2024. The Author(s).)

Purpose: To compare the clinical features and visual outcomes in children and adults with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)., Design: Retrospective comparative case series., Methods: This retrospective study included 280 eyes of 140 patients (35 children and 105 adults) with SJS/TEN treated between 2010 and 2020. The primary outcome measures were the final best-corrected visual acuity (BCVA) and severity of dry eye. The secondary outcome measure was the medical and surgical therapies used., Results: Among 64 eyes of children recruited in the study, acute ocular involvement was found in 58 eyes (90.6%). The chronic score in pediatric patients was significantly higher than that in adult patients (P = .004). The use of antibiotics/nonsteroidal anti-inflammatory drugs (NSAIDs) and Mycoplasma infection were the more common etiologies in children. In all, 75% of eyes in children maintained a visual acuity of 20/40 or better at a mean follow-up time of 4.3 years. The severity of dryness was comparable between the child and adult groups. The proportion of eyes undergoing amniotic membrane and oral mucosa transplantation was significantly higher in children than in adults in the chronic stage, reflecting that children exhibit much more severe complications., Conclusions: Although pediatric SJS/TEN patients have more severe ocular complications than adults, most children maintain long-term good vision. Early intervention and aggressive treatment help to preserve vision., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To compare the survival outcomes between surveillance and adjuvant chemotherapy in patients with stage Ⅰ ovarian immature teratoma (IMT) underwent fertility-sparing surgery. Methods: Clinical and pathological records of patients with stage Ⅰ ovarian IMT between Jan. 2011 to Feb. 2023 were collected from Peking Union Medical College Hospital, except stage Ⅰa grade 1. The consultation of risks and benefits regarding adjuvant chemotherapy was conducted by gynecologic oncologists. A shared decision about surveillance or chemotherapy was made by physician and patients or their guardians. Patients who finally decided to undergo surveillance were included in the surveillance group ( n =40), the others were included in the adjuvant chemotherapy group ( n =63). Clinical characteristics, treatment and survival outcomes were analyzed and compared between two groups. Results: A total of 103 patients were included. The median age of initial diagnosis was 20 years old (range: 3-39 years old), and the median follow-up time was 31 months (range: 1-254 months). The age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, surgical method, and preoperative and postoperative alpha-fetoprotein levels in the surveillance group and the adjuvant chemotherapy group were similar (all P >0.05). The surgical approach and maximum tumor diameter between two groups were significantly different (all P <0.05). Forty patients of the surveillance group were identified, only one patient with stage Ⅰa grade 2 IMT who underwent cystectomy had malignant recurrence on the same ovary. Another 63 patients received adjuvant chemotherapy after surgery, five patients had malignant recurrence, and two of them died of disease progression after relapsed. There were no significant differences in disease-free survival (DFS;20 vs 36 months) and overall survival (OS; 23 vs 39 months) between the surveillance group and the adjuvant chemotherapy group (follow-up time censored at 72 months; DFS: P =0.325, OS: P =0.278). Conclusions: There are no differences in survival outcomes between patients with stage Ⅰ ovarian IMT underwent adjuvant chemotherapy or not. Active surveillance might be safe and preferable in stage Ⅰ IMT patients underwent complete resection of tumor.

Genome-wide association studies have identified numerous single-nucleotide polymorphisms (SNPs) associated with lung cancer; however, the functions of histone deacetylase 2 (HDAC2) rs13213007 and HDAC2 in nonsmall cell lung cancer (NSCLC) remain unclear. Here we identified HDAC2 rs13213007 as a risk SNP and showed that HDAC2 was upregulated in both peripheral blood mononuclear cells (PBMCs) and NSCLC tissues with the rs13213007 A/A genotype compared with those with the rs13213007 G/G or G/A genotype. Patient clinical data indicated strong associations between rs13213007 genotype and N classification. Immunohistochemical staining confirmed that higher expression of HDAC2 was associated with NSCLC progression. Furthermore, we generated 293T cells with the rs13213007 A/A genotype using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing. Chromatin immunoprecipitation sequencing followed by motif analysis showed that HDAC2 can bind to c-Myc in rs13213007 A/A 293T cells. Cell Counting Kit-8, colony formation, wound-healing, and Transwell assays revealed that HDAC2 upregulates c-Myc and cyclin D1 expression and promotes NSCLC cell proliferation, migration, and invasion. Co-immunoprecipitation, quantitative reverse transcription-polymerase chain reaction, and western blot analysis assays showed that MTA3 interacts with HDAC2, decreases HDAC2 expression, and rescues the migration and invasion abilities of NSCLC cells. Taken together, these findings identify HDAC2 as a potential therapeutic biomarker in NSCLC., (© 2023 Wiley Periodicals LLC.)

Objectives: To determine whether dual-energy CT (DECT) can be used to accurately and reliably detect anterior cruciate ligament (ACL) rupture., Materials and Methods: Participants with unilateral ACL rupture were prospectively enrolled, and the bilateral knees were scanned by DECT. A tissue-specific mapping algorithm was applied to improve the visualization of the ACLs. The 80-keV CT value, mixed-keV CT value, electron density (Rho), and effective atomic number (Z eff ) were measured to quantitatively differentiate torn ACLs from normal ACLs. MRI and arthroscopy served as the reference standards., Results: Fifty-one participants (mean age, 27.0 ± 8.7 years; 31 men) were enrolled. Intact and torn ACLs were explicitly differentiated on color-coded DECT images. The 80-keV CT value, mixed-keV CT value, and Rho were significantly lower for the torn ACLs than for the intact ACLs (p < 0.001). The optimal cutoff values were an 80-keV CT value of 61.8 HU, a mixed-keV CT value of 60.9 HU, and a Rho of 51.8 HU, with AUCs of 98.0% (95% CI: 97.0-98.9%), 99.2% (95% CI: 98.6-99.7%), and 99.8% (95% CI: 99.6-100.0%), respectively. Overall, DECT had almost perfect reliability and validity in detecting ACL integrity (sensitivity = 97.1% [95% CI: 88.1-99.8%]; specificity = 98.0% [95% CI: 89.5-99.9%]; PPV = 98.0% [95% CI: 93.0-99.8%]; NPV = 97.1% [95% CI: 91.7-99.4%]; accuracy = 97.5% [95% CI: 94.3-99.2%]). There was no evidence of a difference between MRI and DECT in the diagnostic performance (p > 0.99)., Conclusion: DECT has excellent diagnostic accuracy and reliability in qualitatively and quantitatively diagnosing ACL rupture., Clinical Relevance Statement: DECT could validly and reliably diagnose ACL rupture using both qualitative and quantitative methods, which may become a promising substitute for MRI to evaluate the integrity of injured ACLs and the maturity of postoperative ACL autografts., Key Points: • On color-coded DECT images, an uncolored ACL was a reliable sign for qualitatively diagnosing ACL rupture. • The 80-keV CT value, mixed-keV CT value, and Rho were significantly lower for the torn ACLs than for the intact ACLs, which contributed to the quantitative diagnosis of ACL rupture. • DECT had an almost perfect diagnostic performance for ACL rupture, and diagnostic capability was comparable between MRI and DECT., (© 2023. The Author(s).)

Objective: To investigate the value of net water uptake (NWU) for predicting early neurological improvement (ENI) after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke. Methods: A case-control study. A total of 132 patients (80 men, 52 women, median age 68 years) with acute anterior circulation large vessel occlusive stroke receiving endovascular treatment were retrospectively analyzed at Jinling Hospital from October 2014 to September 2019. Patients were divided into two groups based on the occurrence of ENI, which was defined as either an improvement of NIHSS score of ≥4 points, or an NIHSS score of 0 or 1 at 24 hours after endovascular treatment. The rank sum test, Chi square test, and other methods were used to compare differences in baseline characteristics between the two groups. Logistic regression analysis was used to investigate independent predictors of postoperative ENI. Receiver operating characteristic curve analysis used to assess the capacity of NWU to predict ENI. Results: Of the 132 patients in the study, ENI occurred in 47 and did not occur in 85. In multivariate logistic regression analysis age [odds ratio ( OR )=0.940, 95% confidence interval ( CI ) 0.903-0.979, P =0.003], time from stroke onset to puncture ( OR =0.995, 95% CI 0.991-0.999, P =0.025), time from puncture to recanalization/end of operation ( OR =0.985, 95% CI 0.974-0.996, P =0.007), NWU ( OR =0.762, 95% CI 0.620-0.937, P =0.010), and mTICI ( OR =1.644, 95% CI 1.043-2.590, P =0.032) were predictive factors for ENI. Receiver operating characteristic curve analysis indicated that NWU could effectively predict ENI (area under the curve=0.642, 95% CI 0.543-0.741, P =0.007), and prediction accuracy was improved when it was combined with other clinical parameters. Conclusion: NWU is an independent predictor of ENI in patients with acute anterior circulation large vessel occlusive stroke undergoing endovascular treatment.

Lignocellulosic biomass (LCB) has been recognized as a valuable carbon source for the sustainable production of biofuels and value-added biochemicals. Crude enzymes produced by fungal cell factories benefit economic LCB degradation. However, high enzyme production cost remains a great challenge. Filamentous fungi have been widely used to produce cellulolytic enzymes. Metabolic engineering of fungi contributes to efficient cellulase production for LCB biorefinery. Here the latest progress in utilizing fungal cell factories for cellulase production was summarized, including developing genome engineering tools to improve the efficiency of fungal cell factories, manipulating promoters, and modulating transcription factors. Multi-omics analysis of fungi contributes to identifying novel genetic elements for enhancing cellulase production. Furthermore, the importance of translation regulation of cellulase production are emphasized. Efficient development of fungal cell factories based on integrative strain engineering would benefit the overall bioconversion efficacy of LCB for sustainable bioproduction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P =0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P =0.150) and overall recurrence rate (33% vs 41%; P =0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P <0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence ( OR =23.03, 95% CI : 3.55-149.39, P =0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference ( P =0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P =0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences ( P =0.704, P =0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P =0.860) and OS (56.2 vs 62.4 months; P =0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

Microglial cells are a macrophage-like cell type residing within the CNS. These cells evoke pro-inflammatory responses following thrombin-induced brain damage. Inflammasomes, which are large caspase-1-activating protein complexes, play a critical role in mediating the extracellular release of HMGB1 in activated immune cells. The exact role of inflammasomes in microglia activated by thrombin remains unclear, particularly as it relates to the downstream functions of HMGB1. After receiving microinjections of thrombin, Sprague Dawley rats of 200 to 250 gm were studied in terms of behaviors and immunohistochemical staining. Primary culture of microglia cells and BV-2 cells were used for the assessment of signal pathways. In a water maze test and novel object recognition analysis, microinjections of thrombin impaired rats' short-term and long-term memory, and such detrimental effects were alleviated by injecting anti-HMGB-1 antibodies. After thrombin microinjections, the increased oxidative stress of neurons was aggravated by HMGB1 injections but attenuated by anti-HMGB-1 antibodies. Such responses occurred in parallel with the volume of activated microglia cells, as well as their expressions of HMGB-1, IL-1β, IL-18, and caspase-I. In primary microglia cells and BV-2 cell lines, thrombin also induced NO release and mRNA expressions of iNOS, IL-1β, IL-18, and activated caspase-I. HMGB-1 aggravated these responses, which were abolished by anti-HMGB-1 antibodies. In conclusion, thrombin induced microglia activation through triggering inflammasomes to release HMGB1, contributing to neuronal death. Such an action was counteracted by the anti-HMGB-1 antibodies. The refinement of HMGB-1 modulated the neuro-inflammatory response, which was attenuated in thrombin-associated neurodegenerative disorder.

Purpose: Non-alcoholic fatty liver disease (NAFLD) is considered as both a vital risk factor and a consequence of type 2 diabetes mellitus (T2DM). Low total testosterone (TT) is common in men with T2DM, contributing to increased risks of metabolic diseases. This study aimed to investigate the association between TT levels and the prevalence of NAFLD in men with T2DM., Methods: In this cross-sectional study, 1005 men with T2DM were enrolled in National Metabolic Management Center (MMC) of First Affiliated Hospital of Wenzhou Medical University between January 2017 and August 2021. NAFLD was diagnosed using ultrasound as described by the Chinese Liver Disease Association. Overweight/obesity was defined as body mass index (BMI) ≥ 25 kg/m 2 according to WHO BMI classifications., Results: Individuals without NAFLD had higher serum TT levels than those with NAFLD. After adjustments for potential confounding factors, the top tertile was significantly associated with lower prevalence of NAFLD compared with the bottom tertile of TT level [odds ratio (OR) 0.303, 95% confidence interval (CI) 0.281-0.713; P < 0.001]. The association between TT with NAFLD in individuals with normal weight (OR 0.175, 95% CI 0.098-0.315; P < 0.001) was stronger than in individuals with overweight/obesity (OR 0.509, 95% CI 0.267-0.971; P = 0.040). There was a significant interaction of TT with overweight/obesity (P for interaction = 0.018 for NAFLD)., Conclusion: Higher serum TT was significantly associated with a lower prevalence of NAFLD in men with T2DM. We found that the relationship of TT and NAFLD was stronger in individuals with non-overweight/obesity., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Thrombin is a multifunctional serine protein which is closely related to neurodegenerative disorders. The Aryl hydrocarbon receptor (AhR) is well expressed in microglia cells involving inflammatory disorders of the brain. However, it remains unclear as to how modulation of AhR expression by thrombin is related to the development of neurodegeneration disorders. In this study, we investigated the role of AhR in the development of thrombin-induced neurodegenerative processes, especially those concerning microglia. The primary culture of either wild type or AhR deleted microglia, as well as BV-2 cell lines, was used for an in vitro study. Hippocampal slice culture and animals with either wild type or with AhR deleted were used for the ex vivo and in vivo studies. Simulations of ligand protein docking showed a strong integration between the thrombin and AhR. In thrombin-triggered microglia cells, deleting AhR escalated both the NO release and iNOS expression. Such effects were abolished by the administration of the AhR agonist. In thrombin-activated microglia cells, downregulating AhR increased the following: vascular permeability, pro-inflammatory genetic expression, MMP-9 activity, and the ratio of M1/M2 phenotype. In the in vivo study, thrombin induced the activation of microglia and their volume, thereby contributing to the deterioration of neurobehavior. Deleting AhR furthermore aggravated the response in terms of impaired neurobehavior, increasing brain edema, aggregating microglia, and increasing neuronal death. In conclusion, thrombin caused the activation of microglia through increased vessel permeability, expression of inflammatory response, and phenotype of M1 microglia, as well the MMP activity. Deleting AhR augmented the above detrimental effects. These findings indicate that the modulation of AhR is essential for the regulation of thrombin-induced brain damages and that the AhR agonist may harbor the potentially therapeutic effect in thrombin-induced neurodegenerative disorder.

Objective: To evaluate the efficacy and safety of transdermal drug delivery therapy for schizophrenia with anxiety symptoms., Methods: A total of 80 schizophrenic patients (34 males and 56 females) with comorbid anxiety disorders were randomly assigned to the treatment group ( n  = 40) and the control group ( n  = 40) with 6 weeks of follow-up. The patients in the treatment group received the standard antipsychotic drug treatment along with transdermal drug delivery therapy. The evaluation of the patients included the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD-17), and treatment emergent symptom scale (TESS) at baseline, 3 weeks, and 6 weeks after transdermal drug delivery therapy. The Positive and Negative Symptom Scale (PANSS) was assessed at baseline and after 6 weeks of treatment., Results: After 3 and 6 weeks of treatment, the HAMA scale scores in the treatment group were lower than those in the control group ( p  < 0.001). However, there were no significant differences in the HAMD-17 scale scores, PANSS total scores, and subscale scores between the two groups ( p  > 0.05). Additionally, no significant differences in adverse effects were observed between the two groups during the intervention period ( p  > 0.05). After 6 weeks of penetration therapy, there was a low negative correlation between total disease duration and the change in HAMA scale score (pretreatment-posttreatment) in the treatment group., Conclusion: Combined traditional Chinese medicine directed penetration therapy can improve the anxiety symptoms of patients with schizophrenia and has a safe profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Wang, Zhao, Long, Xiao, Pan, Yuan and Chen.)

Purpose: To evaluate the extent of tunnel widening after anterior cruciate ligament reconstruction (ACLR) using the all-inside technique and to establish its correlation with patient-reported clinical outcomes and femoral graft bending angle (GBA)., Methods: Tunnel widening was evaluated using computed tomography (CT)-based three-dimensional (3D) models, and the femoral GBA was directly measured on CT images using the Picture Archiving and Communication System (PACS) software. Clinical follow-up was routine procedure, and patient-reported clinical outcomes mainly included International Knee Documentation Committee (IKDC), Lysholm, and Knee Injury and Osteoarthritis Outcome Scores (KOOS) scores, and subjective knee stability assessment., Results: Fifty-two patients received standard all-inside ACLR, with a median follow-up of 6 months. Reconstructed anterior cruciate ligaments (ACLs) were scanned during the first 3 days and 6 months after surgery. On both the femoral and tibial sides, bone tunnels were most significantly enlarged at the articular aperture segment; the femoral tunnel was 9.2 ± 1.3 mm postoperatively and was significantly enlarged by 32% to a mean tunnel diameter of 12.1 ± 2.0 mm at 6 months after surgery. Moreover, the extent of tunnel enlargement gradually decreased as the measured levels approached those of the bone cortex. The femoral tunnel center was shifted into the anterior and distal direction, and the tibial tunnel center was shifted into the posterior and lateral direction. Additionally, the mean femoral GBA was 105.9° ± 8.1° at the 6-month follow-up. Tunnel enlargement and GBA were not significantly correlated with patient-reported outcomes., Conclusions: Femoral and tibial tunnels were significantly greater and eccentrically shifted at the 6-month follow-up after all-side ACLR. However, the extent of tunnel widening does not markedly affect the short-term clinical outcomes. Meanwhile, the femoral GBA was not significantly correlated with femoral tunnel widening or patient-reported outcomes. Although the tunnel widening following all-inside ACLR was not associated with clinical outcomes, it potentially caused difficulties in revision ACLR., Level of Evidence: Level IV., (© 2022. The Author(s).)

Recently, water promotion effects in the selective oxidation of benzyl alcohol to benzaldehyde have been experimentally recognized and identified. However, the effects of water on the photocatalytic selective oxidation of toluene into benzaldehyde remain elusive. In this work, the Ti 3 O 9 H 6 clusters in different solvents (water and toluene solvent) are used to study the water-induced effects in photocatalytic oxidation reactions in kinetics and thermodynamics using density functional theory (DFT) calculations. In addition, the influences of the OH groups on catalysts (Ti-OH bonds) from photocatalytic water splitting are also considered. The results clearly demonstrate the water-induced double-edged sword effects in the photocatalytic selective oxidation of toluene. We expect that our work can not only shed light on the mechanisms of photocatalytic selective oxidation of toluene into benzaldehyde and other activation reactions of sp 3 C-H bonds but also design and modulate highly efficient photocatalysts.

Purpose: Our purpose was to assess job stress and burnout among anesthesiologists in the tertiary class A hospitals in Northwest China, analyze the possible causes and adverse consequences of increased job stress and burnout of anesthesiologists in this region, and put forward suggestions in combination with the current national policies., Methods: We sent 500 electronic questionnaires to all anesthesiologists practicing in the tertiary class A hospitals in Northwest China from 1960 to 2017 on April 2020. A total of 336 (67.2%) questionnaires were returned and could be used for analysis. Burnout and job stress were assessed by using the modified Maslach Burnout Inventory-Human Services Survey and Chinese Perceived Stress Scale, respectively., Results: First, as for emotional exhaustion, the situations of anesthesiologists with different working years and workloads are different with statistical significance ( P < 0.05). Second, as for depersonalization, the situations of anesthesiologists with different ages, professional titles, working years, physical health status, and workload are different ( P < 0.05). Third, as for personal accomplishment, the situations of anesthesiologists with different physical health status are different ( P < 0.05). Finally, the regression results showed that the longer the fatigue working years and the worse the physical health of anesthesiologists in Northwest China, the more likely these two factors were to cause burnout ( P < 0.05), as for job stress, there was a negative correlation between job stress and physical health status ( P < 0.05)., Conclusion: Burnout and high job pressure are common among anesthesiologists in tertiary class A hospitals in Northwest China. We should focus on the allocation of labor intensity, pay attention to the physical and mental health of employees, establish targeted incentive mechanism, and improve the system of promotion and income rises for grassroots doctors. This may be not only conducive to the quality of medical care for patients but also conducive to the development of anesthesiology in China., Trial Registration: Identifier: ChiCTR2000031316., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Pan, Fu, Qing, Dong and Ye.)

The subgenus Cerasus , one of the most important groups in the genus Prunus sensu lato , comprises over 100 species; however, the taxonomic classification and phylogenetic relationships of Cerasus remain controversial. Therefore, it is necessary to reconstruct the phylogenetic tree for known Cerasus species. Here, we report the chloroplast (cp) genome sequences of 11 Cerasus species to provide insight into evolution of the plastome. The cp genomes of the 11 Cerasus species (157,571-158,830 bp) displayed a typical quadripartite circular structure. The plastomes contain 115 unique genes, including 80 protein-coding genes, four ribosomal RNAs, and 31 transfer RNAs. Twenty genes were found to be duplicated in inverted repeats as well as at the boundary. The conserved non-coding sequences showed significant divergence compared with the coding regions. We found 12 genes and 14 intergenic regions with higher nucleotide diversity and more polymorphic sites, including matK , rps16 , rbcL , rps16 - trnQ , petN - psbM , and trnL - trnF . During cp plastome evolution, the codon profile has been strongly biased toward the use of A/T at the third base, and leucine and isoleucine codons appear the most frequently. We identified strong purifying selection on the rpoA , cemA , atpA , and petB genes; whereas ccsA , rps19 , matK , rpoC2 , ycf2 and ndhI showed a signature of possible positive selection during the course of Cerasus evolution. In addition, we further analyzed the phylogenetic relationships of these species with 57 other congenic related species.Through reconstructing the Cerasus phylogeny tree, we found that true cherry is similar to the flora of China forming a distinct group, from which P. mahaleb was separated as an independent subclade. Microcerasus was genetically closer to Amygdalus , Armeniaca , and Prunus ( sensu stricto ) than to members of true cherry, whereas P. japonica and P. tomentosa were most closely related to P. triloba and P. pedunculata . However, P. tianshanica formed a clade with P. cerasus , P. fruticosa , P. cerasus × P. canescens 'Gisela 6', and P. avium as a true cherry group. These results provide new insights into the plastome evolution of Cerasus , along with potential molecular markers and candidate DNA barcodes for further phylogenetic and phylogeographic analyses of Cerasus species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wan, Qiao, Zhou, Shao, Pan, An, He, Liu, Li and Cai.)

Purpose: Microsurgery is the mainstay of treatment for large vestibular schwannomas (VS), but the benefits of radiosurgery remain incompletely defined. Here, we aim to use automated volumetric analysis software to quantify the degree of brain stem deformity to predict long-term outcomes of patients with large VS following GKRS., Methods: Between 2003 and 2020, 39 patients with large VS (volume > 8 cc) undergoing GKRS with a margin dose of 10-12 Gy were analyzed. The reconstruction 3D MRI was used to evaluate the extent of deformity for predicting the long-term outcome of patients., Results: Their mean tumor volume was 13.7 ± 6.3 cc, and their mean follow-up after GKRS was 86.7 ± 65.3 months. Favorable clinical outcome was observed in 26 (66.7%) patients, while 13 (33.3%) patients had treatment failure. Patients with small tumor volumes, low vital structure deformity indice [(TV/(BSV + CerV) and (TV + EV)/(BSV + CerV)], and long distance of tumor to the central line were more likely to have favorable clinical outcome after GKRS. Significant prognostic value was with tumor shrinkage ratio (< 50%) were CV, CV/TV, TV/CerV, (TV + EV)/(BSV + CerV), and the distance of tumor to the central line. In cox regression, favorable clinical outcome was correlated with the Charlson comorbidity index and cochlear dosage (both p < 0.05). In multivariant analysis, tumor regression was highly correlated with the CV/TV ratio (p < 0.001)., Conclusions: The brainstem deformity ratio is likely a useful index to assess the clinical and tumor regression outcomes. Clinical outcomes are multifactorial and the tumor regression was highly correlated with the ratio of cystic components., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alternaria alternata is a necrotrophic fungal pathogen with a broad host range that causes widespread and devastating disease in sweet cherry ( Prunus avium ). We selected a resistant cultivar (RC) and a susceptible cultivar (SC) of cherry and used a combined physiological, transcriptomic, and metabolomic approach to investigate the molecular mechanisms underlying the plant's resistance to A. alternata , of which little is known. We found that A. alternata infection stimulated the outbreak of reactive oxygen species (ROS) in cherry. The responses of the antioxidant enzymes and chitinase to disease were observed earlier in the RC than in the SC. Moreover, cell wall defense ability was stronger in the RC. Differential genes and metabolites involved in defense responses and secondary metabolism were primarily enriched in the biosynthesis of phenylpropanoids, tropane, piperidine and pyridine alkaloids, flavonoids, amino acids, and α-linolenic acid. Reprogramming the phenylpropanoid pathway and the α-linolenic acid metabolic pathway led to lignin accumulation and early induction of jasmonic acid signaling, respectively, in the RC, which consequently enhanced antifungal and ROS scavenging activity. The RC contained a high level of coumarin, and in vitro tests showed that coumarin significantly inhibited A. alternata growth and development and had antifungal effect on cherry leaves. In addition, differentially expressed genes encoding transcription factors from the MYB, NAC, WRKY, ERF, and bHLH families were highly expressed, they could be the key responsive factor in the response of cherry to infection by A. alternata . Overall, this study provides molecular clues and a multifaceted understanding of the specific response of cherry to A. alternata ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pan, Zhou, Sun, Qiao, Wan, Guo, Zhang, Shan and Cai.)

Given the problems of unclear division of evaluation factors, inadequate utilization of objective data and unreasonable distribution of weight in college performance measurement, this study extracts relevant indicators and quantitative data from the survey report of administrational institutions, and constructs a comprehensive performance measurement model based on the integration of fuzzy Delphi method (FDM), Entropy weight method (EWM), and grey relational analysis (GRA). The study seeks to identify differences in measurement analysis by comparing the weights, the performance and the rankings of the alternatives about higher vocational colleges in Zhejiang province. Finally, the results show the following: (1) by FDM, 33 indicators about colleges' performance are selected to form the evaluation system of the college's performance, (2) the indicators' weights are obtained through EWM and GRA, and a nonparametric test shows that there is no significant difference between the two types of weights, (3) the grey relational degrees of the alternatives are obtained and ranked on the basis of comprehensive evaluation model. By nonparametric test, there is a significant difference between the two types of relational degrees. On the contrary, no significant difference is found in the ranking of relational degrees, (4) based on the analysis results, this study further compares the performance of alternatives in different forms. There are significant differences between the performance of public colleges and private colleges, while no significant differences are observed between the performance of vocational colleges in Hangzhou and non-Hangzhou. Given the reliability and validity of the model, the comprehensive measurement model provides a relatively objective reference for college governance and administrational institutions, and also becomes an effective tool of colleges' evaluation to assist and improve the management practice in educational institutions., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Introduction: The aim of this study was to investigate the associations of neck circumference (NC) and neck-to-height (NHR) with diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: A total of 2,615 patients with prevalent T2DM were enrolled. NHR was calculated through NC (cm) divided by height (cm), and prevalent DKD was defined as the urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g or the estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m 2 in the absence of other primary kidney diseases., Results: The levels of NC and NHR were higher in DKD patients compared with non-DKD patients (38.22 vs. 37.71, P = 0.003; 0.232 vs. 0.227, P < 0.001, respectively). After full adjustments, individuals at the highest tertile of NHR had higher odds of DKD than those at the lowest tertile (multivariate-adjusted OR = 1.63, 95% CI: 1.22, 2.18), but this association was not pronounced with NC (multivariate-adjusted OR = 1.24, 95% CI: 0.87, 1.76). Individuals at the highest tertile of NHR had lower eGFR (β = -4.64, 95% CI: -6.55, -2.74) and higher UACR levels (β = 0.27, 95% CI: 0.10, 0.45) than those at the lowest tertile. The adverse association between NHR and prevalent DKD remained statistically significant among most of the subgroups analyzed and no interaction effects were observed., Conclusion: The increase in NHR was adversely and independently associated with DKD in this Chinese T2DM population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 He, Gu, Du, Hu, Zhang, Yang, Li, Li, Pan, Yang, Gu and Lin.)

Purpose: The purpose of this study was to analyze the clinical features, causative microorganisms, antibiotic susceptibility, and treatment outcomes in culture-proven microbial keratitis (MK) in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and to analyze the potential risk factors., Methods: We reviewed the medical records of all patients with SJS/TEN who attended our department between 2009 and 2018. Patients with a diagnosis of MK who underwent corneal cultures were enrolled. Demographics; clinical characteristics including ocular findings, treatment, time between onset of SJS/TEN and keratitis; changes in visual acuity; culture results; and antibiotic susceptibility were analyzed. Culture results from prior conjunctival swabs and keratitis were also compared., Results: Sixteen eyes from 12 patients (mean age 40.1 ± 27.7 years) with MK were identified. These patients had the most severe ocular involvement in the acute stage and had more severe ocular complications (SOCs) in the chronic stage compared with patients with SJS/TEN without MK. There were 26 infection episodes during 4.4 ± 6.9 (1.0-25.8) years of follow-up. Oral nonsteroidal anti-inflammatory drugs accounted for half of the causative drugs. Severe dry eye was the most common predisposing factor, followed by topical steroid use, trichiasis, and lid margin keratinization. Staphylococcus was the most common pathogen, and over half of the gram-positive bacteria were resistant to oxacillin/methicillin. Fungal infections (notably Candida ) accounted for nearly one-third of the causative microorganisms. Culture reports from periodic conjunctival swabs were not consistent with those from corneal scrapings. Recurrence of infection was associated with inferior visual outcome., Conclusions: Patients with SJS/TEN with SOCs are subject to recurrent corneal infections, which are responsible for deterioration of vision. Identifying the risk factors and aggressive treatment as early as possible is pivotal for infection control., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The flavor and aroma quality of green tea are closely related to the harvest season. The aim of this study was to identify the harvesting season of green tea by alcohol/salt-based aqueous two-phase system (ATPS) combined with chemometric analysis. In this paper, the single factor experiments (SFM) and response surface methodology (RSM) optimization were designed to investigate and select the optimal ATPS. A total of 180 green tea samples were studied in this work, including 86 spring tea and 94 autumn tea. After the active components in green tea samples were extracted by the optimal ethanol/(NH 4 ) 2 SO 4 ATPS, the qualitative and quantitative analysis was realized based on HPLC-DAD combined with alternating trilinear decomposition-assisted multivariate curve resolution (ATLD-MCR) algorithm, with satisfactory spiked recoveries (86.00 %-112.45 %). The quantitative results obtained from ATLD-MCR model were subjected to chemometric pattern recognition analysis. The constructed partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) models showed better results than the principal component analysis (PCA) model, and the R 2 X cum values (>0.835) and R 2 Y cum (>0.937) were close to 1, the Q 2 cum values were greater than 0.75 (>0.933), and the differences between R 2 Y cum and Q 2 cum were not larger than 0.2, indicating excellent cross-validation prediction performance of the models. Furthermore, the classification results based on the hierarchical clustering analysis (HCA) were consistent with the PCA, PLS-DA and OPLS-DA results, establishing a good correlation between tea active components and the harvesting seasons of green tea. Overall, the combination of ATPS and chemometric methods is accurate, sensitive, fast and reliable for the qualitative and quantitative determination of tea active components, providing guidance for the quality control of green tea., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant tumor of the central nervous system. GBM has a very low 5-year survival rate and reaching merely a median of ~15 months even with aggressive treatments. PPARγ (Peroxisome proliferator- activated receptor gamma) agonists (ciglitazone), while being widely used on patients of type 2 diabetes mellitus, also have approved anticancer effects. Their action mechanisms on malignant glioma are not fully understood. The aim of this study is to investigate the potential therapeutic effect of PPARγ agonists on maligant glioma. Glioma cell line and in-vivo/ex-vivo animal model intervened by ciglitazone were used to assess the associated mechanism and therapeutic effect. Our results from in vivo and ex vivo experiments showed that ciglitazone not only inhibited tumor growth and its associated angiogenesis, but it also reduced colony formation and migration of tumors. Ciglitazone inhibited the phosphorylation of STAT3 (signal transducer and activator of transcription 3) (at the point of tyrosine 705 by increasing both the amount and activity of SHP-2 (Src homology region 2-containing protein tyrosine phosphatase 2) proteins, based on evidence obtained from immunoprecipitation and immunohistochemistry. Furthermore, ciglitazone activated proteasomes and lysosomes to degrade cell-cycle-related proteins like Cyclin D1, Cyclin E, CDK2 (Cyclin-dependent kinase 2), and CDK4 (Cyclin-dependent kinase 4). Ciglitazone triggered expressions of LC3 (Microtubule-associated protein 1A/1B-light chain 3) and formation of acidic vesicular organelles (AVOs), both of which were implicated in the autophagy pathway. In conclusion, ciglitazone showed the multiple actions to regulate the growth of glioma, which appeared to be a potential candidate for treating malignant glioma.

Purpose: Gamma knife radiosurgery (GK) is a commonly used approach for the treatment of intracranial lesions. Its radiation response is typically not immediate, but delayed. In this study, we analyzed cases from a prospectively collected database to assess the influence of COVID-19 pandemic on the decision making in patients treated by gamma knife radiosurgery., Methods: From January 2019 to August 2021, 540 cases of intracranial lesions were treated by GK with 207 cases before COVID-19 pandemic as a control. During the COVID-19 pandemic, 333 cases were similarly treated on patients with or without the COVID-19 vaccination. All the GK treated parameters as well as time profile in the decision making were analyzed. The parameters included age, sex, characteristic of lesion, targeted volume, peripheral radiation dose, neurological status, Karnofsky Performance Status (KPS), time interval from MRI diagnosis to consultation, time interval from the approval to treatment, frequency of outpatient department (OPD) visit, and frequency of imaging follow-up., Results: Longer time intervals from diagnosis to GK consultation and treatment were found in the pandemic group (36.8 ± 25.5/54.5 ± 27.6 days) compared with the pre-COVID control (17.1 ± 22.4/45.0 ± 28.0 days) or vaccination group (12.2 ± 7.1/29.6 ± 10.9 days) (p < 0.001, and p < 0.001, respectively). The fewer OPD visits and MRI examinations also showed the same trends. High proportion of neurological deficits were found in the pandemic group (65.4%) compared with the control (45.4%) or vaccination group (58.1%) (p < 0.001). The Charlson comorbidity in the pandemic group was 3.9 ± 3.3, the control group was 4.6 ± 3.2, and the vaccination group was 3.1 ± 3.1. There were similar inter-group difference (p < 0.001). In multiple variant analyses, longer time intervals from the diagnosis to consultation or treatment, OPD frequency and MRI examination were likely influenced by the status of the COVID-19 pandemic as they were alleviated by the vaccination., Conclusions: The decision making in patients requiring gamma knife treatment was most likely influenced by the status of the COVID-19 pandemic, while vaccination appeared to attenuate their hesitant behaviors. Patients with pre-treatment neurological deficits and high co-morbidity undergoing the gamma knife treatment were less affected by the COVID-19 pandemic., (© 2022. The Author(s).)

We aimed to investigate the association of fruit and vegetable consumption with nonalcoholic fatty liver disease (NAFLD) in Chinese patients with type 2 diabetes mellitus (T2DM). This cross-sectional study included 2667 Chinese patients with T2DM aged 18 to 76 years from March 2017 to October 2021. Dietary intake was assessed using a food frequency questionnaire, and prevalent NAFLD was diagnosed with abdominal ultrasonography. High fruit−vegetable consumption was determined using ≥500 g/day consumption of both fruit and vegetable, and both fruit and vegetable consumption were divided into three categories of <200 g/day (low), 200−400 g/day (median) and >400 g (high). The primary outcome measurement was multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the prevalence of NAFLD in relation to the highest fruit and (or) vegetable intake compared with the lowest. Secondary analyses were conducted to assess the effects of either fruit or vegetable intake on the fatty liver index (FLI) using multivariable linear regressions. There were 1694 men and 973 women in this study, and 1445 (54.06%) participants had prevalent NAFLD. Patients with high fruit−vegetable intake had a lower prevalence of NAFLD than those with low fruit−vegetable intake (52.04% vs. 56.48%), but this difference was not statistically significant (p = 0.065). Vegetable intake had a significantly inverse association with NAFLD (OR: 0.68, 95% CI: 0.52−0.90), but this association was not pronounced with fruit intake (OR: 1.23, 95% CI: 0.89−1.69) or fruit−vegetable intake (OR: 0.90, 95% CI: 0.73−1.10). Additional analyses showed that an increase in vegetable intake was linearly associated with a significant reduction in FLI (β: −1.028, 95% CI: −1.836, −0.219). In conclusion, higher vegetable consumption was associated with lower odds of NAFLD in Chinese patients with T2DM, which suggested that increased vegetable intake might protect patients with diabetes against NAFLD.

There are many reasons for entrepreneurs to start a business, but there is only a thin line between success and failure, and not everyone is willing to try to start a business again after encountering a failure. Therefore, it is worth exploring how start-up losers accumulate the energy of entrepreneurship and the reasons for starting a business again. In this study, the typical sampling method was adopted to select a suitable and representative case company entrepreneur for an in-depth interview. The results of this study revealed that in the process of the Entrepreneur starting a business three times, the Entrepreneur's personal motivation and learning ability in the face of failure, coupled with family support, made the Entrepreneur willing to keep trying, even though he had to face the risk of repeated entrepreneurial failures, so that he could keep his positive energy on his entrepreneurial journey and eventually achieve a successful outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pan, Tsai, Popan and Chang.)

Pseudasphondylia species (Diptera: Cecidomyiidae) are known to induce fruit galls on Actinidia rufa (Siebold & Zucc.) Planch. ex Miq. and finger-like leaf galls on Elaeocarpus sylvestris (Lour.) Poir. in Taiwan, but their taxonomic positions remain undetermined. Based on gall morphology and host plants, they were supposed to be the same or allied species of known Japanese congeners, i.e. , P. matatabi Yuasa & Kumazawa inducing flower-bud galls on Actinidia polygama (Sieb. et Zucc.) Maxim and P. elaeocarpi Tokuda & Yukawa inducing finger-like leaf galls on E. sylvestris . Species identifications of these Taiwanese species provide us an opportunity to study biogeographical aspects and transition of ecological features in these Pseudasphondylia species distributed in East Asian Arc. Morphological comparisons and species delimitation by molecular analysis indicated that the cecidomyiid on the fruit of A. rufa is distinct from P. matatabi and thus it is described as a species new to science, P. kiwiphila sp. nov. Lin, Tokuda, & Yang. The leaf galler on E. sylvestris was identical to P. elaeocarpi , whose southernmost distribution range extended to Taiwan, a new record of its distribution. COI -based phylogenetic tree (Bayesian inference and IQ tree) of Pseudasphondylia suggested that leaf galling habitat and univoltine life history are ancestral, whereas fruit or flower-bud galling and multivoltine life history are derived. In addition, the monophyletic Actinidia -associated species lineage is sistered to the clade including the remaining Japanese fruit and flower-bud gallers, suggesting that Pseudasphondylia has colonized on the host genus Actinidia once and later speciated on different plant species of the host genus. As a biogeographical aspect of P. elaeocarpi , 2.7% of the COI distance between Japanese and Taiwanese individuals indicates that they have diverged around 1.2 mya, which corresponds to the last but second separation of Taiwan and Japan in the Pleistocene. As for Actinidia -associated Pseudasphondylia species, the two valid species are allopatric and have distinct areas of origin, suggesting they may have speciated allopatrically. Nevertheless, there is still the possibility of ecological speciation due to the following reasons: (1) Host species (and varieties) and unidentified congener of Actinidia -associated Pseudasphondylia are occurring China, revealing potential occurrence of these gall midges. (2) The divergence time (2.2-2.9 mya) of the two known species corresponds to the late Pliocene to Pleistocene, when China, Taiwan, and Japan were part of the East Asian continent. During this period, their host species were sympatric in southeast China. (3) The host of two named Actinidia -associated Pseudasphondylia species each belong to different plant groups with distinct fruit features. These presume that the speciation might have been caused via sympatric host shift.

We studied longitudinal changes in the microbiome with weight gain during atypical antipsychotics (APs) treatment. 43 inpatients naive to AP paediatric medication were included in the longitudinal microbiota study. The baseline composition of the gut microbiome in the case group was characterised by an increase in Parabacteroides and Eubacterium&#95;hallii&#95;group. During the follow-up, the relative abundances of Romboutsia and Klebsiella increased significantly after 3 months of AP treatment; however, no significant changes in these two gut bacteria were observed in the control group. The baseline composition of the gut microbiome contributed to the risk of AP-associated weight gain., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: This study is aimed at investigating whether relaxin-3 exhibits protective effects against cardiomyopathy in diabetic rats by suppressing ERS., Methods: Eighty male SD rats were randomly divided into two groups: controls ( n = 20) and diabetes ( n = 60). The streptozotocin-treated rats were randomly divided into three groups: diabetic group (DM), low-dose relaxin-3 group (0.2  μ g/kg/d), and high-dose relaxin-3 group (2  μ g/kg/d). The myocardial tissues and collagen fiber were observed by hematoxylin and eosin (H&E) and Masson staining. Serum brain natriuretic peptide (BNP), troponin (TNI), myoglobin, interleukin (IL-17), interleukin (IL)-1 α , and tumor necrosis factor (TNF)- α were determined by ELISA. The protein expression of glucose regulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the heart tissue of each group was detected by Western blot analysis., Results: (1) HE and Masson staining indicated that relaxin-3 could attenuate myocardial lesions and myocardial collagen volume fraction. (2) BNP, TnI, and myoglobin in the DM group at four and eight weeks were significantly higher than in the controls ( P < 0.01). The relaxin-3-treated groups showed significantly reduced serum BNP, TnI, and myoglobin levels compared with the DM group ( P < 0.05). (3) IL-17, IL-1 α , and TNF- α levels in the DM rats at 4 weeks were higher than in the controls ( P < 0.05). Low or high dose of relaxin-3-treated groups showed reduced serum IL-17 and TNF- α levels compared with the DM group at four and eight weeks ( P < 0.05). (4) CHOP and GRP78 protein expression was increased in the DM group at four and eight weeks compared with the controls ( P < 0.01), and small and large doses of relaxin-3 significantly reduced GRP78 and CHOP protein expression., Conclusions: Exogenous relaxin-3 ameliorates diabetic cardiomyopathy by inhibiting ERS in diabetic rats., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Li-ya Pan et al.)

Neuropathic pain is well known to occur after damage to the somatosensory system. Aryl hydrocarbon receptor (AhR) has neuroprotective effects when the central nervous system is subjected to internal and external stimulations. However, the exact mechanism by which AhR regulates neuropathic pain is poorly understood. Nerve explant culture and the chronic constrictive nerve injury (CCI) model in wild or AhR-knockout mice were used in this study. In the nerve explant culture, the ovoid number increased in the AhR-/- condition and was decreased by omeprazole (AhR agonist) in a dose-dependent manner. Increased nerve degeneration and the associated inflammation response appeared in the AhR-/- condition, and these changes were attenuated by omeprazole. High expression of AhR in the injured nerve was noted after CCI. Deletion of AhR aggravated nerve damages and this was restored by omeprazole. Deletion of AhR increased NGF expression and reduced axon number in the paw skin, but this was attenuated by omeprazole. A highly expressed inflammation reaction over the dorsal spinal cord, somatosensory cortex, and hippocampus was noted in the AhR-deleted animals. Administration of omeprazole attenuated not only the inflammatory response, but also the amplitude of somatosensory evoked potential. Deletion of AhR further aggravated the neurobehavior compared with the wild type, but such behavior was attenuated by omeprazole. Chronic constrictive nerve injury augmented AhR expression of the injured nerve, and AhR deletion worsened the damage, while AhR agonist omeprazole counteracted such changes. AhR agonists could be potential candidates for neuropathic pain treatment.