Hu'po Anshen decoction promotes fracture healing in mice with traumatic brain injury through BMP2-COX2-ATF4 signaling pathway.

Hu'po Anshen decoction (HPASD), a traditional Chinese medicine used to treat concussion and fracture, could regulate the expression of bone morphogenetic protein 2 (BMP2). However, whether HPASD affects the fracture healing of traumatic brain injury (TBI) combined with a fracture through BMP2 and its downstream signals remains obscure. The chondrocyte-specific BMP2 conditional knockout mice and chondrocyte-specific cyclooxygenase-2 (COX2) overexpression mice were generated. BMP2 conditional knockout mice were treated with fracture surgery, fracture combined with TBI, or fracture combined with TBI followed by different doses of HPASD (2.4, 4.8, and 9.6 g/kg), respectively. TBI was induced by Feeney's weight-drop technique. The fracture callus formation and fracture sites were determined by X-ray, micro-CT, and histological analyses. The expressions of chondrocyte-, osteoblast-, and BMP2/COX2 signal-related targets were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot assays. The specific absence of BMP2 in chondrocytes led to the prolonged formation of cartilage callus, a delay in the osteogenesis initiation and the downregulation of RUNX2, Smad1/5/9, EP4, ERK1/2, RSK2, ATF4. Overexpression of COX2 partially reverses the effects of chondrocyte-specific BMP2 knockout mice. HPASD promoted cartilage callus formation and osteogenesis initiation, as accompanied by upregulated expression levels of RUNX2, Smad1/5/9, EP4, ERK1/2, RSK2, and ATF4 in a time-dependent and concentration-dependent manner in chondrocyte-specific BMP2 knockout mice. Overall, our findings demonstrated that HPASD induced COX2 transcription through the BMP2-Smad1/5/9-RUNX2 axis, and then affected fracture healing through the COX2-mediated EP4-ERK1/2-RSK2-ATF4 axis.

KISS-1 knockdown inhibits cell growth, migration, and invasion in HTR-8/SVneo cells by regulating the GRP54-mediated PI3K/AKT signaling pathway.

Recurrent spontaneous abortions (RSA) affect reproductive health and increase the risk of subsequent abortions. To investigate the role of KISS-1/GPR-54 signaling in RSA progression. Villus tissue was collected from RSA patients, and human trophoblastic HTR-8/SVneo cells were used. KISS-1 and GRP54 levels were detected using RT-qPCR and immunohistochemistry. Western blotting was performed to analyze ZO-1 and ZEB1 levels. Cell proliferation was determined via CCK-8 and cell clone formation assays. Transwell assays were performed to assess cell migration and invasion abilities. KISS-1 was down-regulated in the villus tissues of RSA patients. KISS-1 overexpression dramatically inhibited trophoblast proliferation, migration, and invasion. Mechanistically, ZEB1 expression was down-regulated, whereas ZO-1 expression was up-regulated, after KISS-1 overexpression. GPR54 silencing neutralized the effect of KISS-1 in HTR-8/SVneo cells. Additionally, KISS-1 overexpression inactivated the PI3K/AKT signaling pathway through GRP54. The KISS-1/GPR-54 signaling axis regulates RSA progression by regulating the PI3K/AKT signaling pathway.

The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis.

INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.

Association of miR-203 Expression with Prognostic Value in Patients with Esophageal Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aims to investigate the association between miR-203 expression and the prognostic value in patients with esophageal cancer by the method of systematic review and meta-analysis. METHODS: We searched PubMed, Web of Science, Embase, and Cochrane Library to collect studies on the relationship between miR-203 expression and the prognostic value of esophageal cancer up to July 2023. Stata 15.0 statistical software was used for data analysis. Hazard ratio (HR) and 95% confidence interval (CI) were used as effect sizes. RESULTS: A total of 6 studies were included in this review, including 476 patients with esophageal cancer. The results showed that miR-203 low expression was associated with worse overall survival (OS) in patients with esophageal cancer compared with miR-203 high expression (HR = 2.80, 95%CI: 1.99 ∼ 3.93, p < 0.001). The results of Egger's (p = 0.154) and Begg's Tests (p = 0.221) indicated no obvious publication bias. Sensitivity analysis verified the robustness of the results obtained in this study. CONCLUSION: The expression of miR-203 is significantly correlated with the prognostic value in patients with esophageal cancer. Esophageal cancer patients with high expression of miR-203 had better prognosis than those with low expression of miR-203. Due to the limited studies included in this meta-analysis, more trials are needed to confirm the conclusions of this study in the future.

Attention-Guided Partial Domain Adaptation for Automated Pneumonia Diagnosis From Chest X-Ray Images.

Deep neural networks (DNN) supported by multicenter large-scale Chest X-Ray (CXR) datasets can efficiently perform tasks such as disease identification, lesion segmentation, and report generation. However, the non-ignorable inter-domain heterogeneity caused by different equipment, ethnic groups, and scanning protocols may lead to dramatic degradation in model performance. Unsupervised domain adaptation (UDA) methods help alleviate the cross-domain discrepancy for subsequent analysis. Nevertheless, they may be prone to: 1) spatial negative transfer: misaligning non-transferable regions which have inadequate knowledge, and 2) semantic negative transfer: failing to extend to scenarios where the label spaces of the source and target domain are partially shared. In this work, we propose a classification-based framework named attention-guided partial domain adaptation (AGPDA) network for overcoming these two negative transfer challenges. AGPDA is composed of two key modules: 1) a region attention discrimination block (RADB) to generate fine-grained attention value via lightweight region-wise multi-adversarial networks. 2) a residual feature recalibration block (RFRB) trained with class-weighted maximum mean discrepancy (MMD) loss for down-weighing the irrelevant source samples. Extensive experiments on two publicly available CXR datasets containing a total of 8598 pneumonia (viral, bacterial, and COVID-19) cases, 7163 non-pneumonia or healthy cases, demonstrate the superior performance of our AGPDA. Especially on three partial transfer tasks, AGPDA significantly increases the accuracy, sensitivity, and F1 score by 4.35%, 4.05%, and 1.78% compared to recently strong baselines.

Function, quality-of-life and complications after sacrospinous ligament fixation using an antegrade reusable suturing device (ARSD-Ney) at 6 and 12 months: a retrospective cohort study.

Background: Pelvic organ prolapse (POP) is a common pathology in the female population. Sacrospinous ligament fixation (SSLF) is one of the traditional transvaginal procedures for POP and high sacrospinous ligament fixation (h-SSLF) optimizes it using an antegrade reusable suturing device (ARSD-Ney). Previous studies on h-SSLF have focused on the correction of anatomical positions, with less assessment of patients' function, quality of life and complications. In this study, we evaluated post-operative complications, function, and quality-of-life after h-SSLF to confirm the safety and effectiveness of it. Methods: This was a retrospective cohort study that included 71 patients between 2018 and 2021: 50 patients for h-SSLF and 21 patients for laparoscopic sacrocolpopexy (LSC) according to patient age and background, POP-Q stage, patient preference, and so on. A clinical evaluation took place before surgery and was repeated at 6 and 12 months postoperatively. Intra- and post-operative complications and anatomical results were recorded. Patients completed self-administered questionnaires for functional pelvic problems [Pelvic Floor Disability Index-20 (PFDI-20)], quality of life [Pelvic Floor Impact Questionnaire-7 (PFIQ-7)], and sexual function [Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12)] at each medical visit. Results: Patients in both h-SSLF and LSC groups were similar in terms of demographic characteristics except for surgery time (86.04±28.70 vs. 153.19±54.88, P<0.05), postoperative indwelling catheter time (3.88±1.65 vs. 4.90±1.84, P<0.05), and hospital stay (8.94±2.38 vs. 10.57±2.06, P<0.05). There were no statistically significant differences between the 2 groups in scores of PFDI-20, PFIQ-7, and PISQ-12 at pre- and post-operative 6 and 12 months (P>0.05). Functional pelvic problems (PFDI-20 scores) and their impact on patients' quality of life (PFIQ-7 scores) significantly improved at 6 and 12 months postoperatively (P<0.05). Improvements in sexual activity were noted at 6 and 12 months postoperatively (P<0.05). Conclusions: This retrospective cohort study confirmed the positive results of h-SSLF in terms of improvement in function and quality of life following treatment for pelvic organ prolapse.

Hyperthermia enhances the efficacy of chemotherapeutic drugs in heat-sensitive cells through interfering with DNA damage repair.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be clinically effective, but the mechanisms by which hyperthermia enhances the sensitivity of cells to chemotherapeutic drugs has not yet been elucidated. Methods: To identify the key molecules involved in thermochemotherapy, this study used mass spectrometry (MS)-based quantitative proteomics technology to analyze the effects of thermochemotherapy on the heat-sensitive ovarian cancer cell line A2780. We divided the A2780 cell line into four groups, one group served as blank control, and the other three groups were stimulated by oxaliplatin, stimulated by hyperthermia at 42 ℃, and stimulated by hyperthermia combined with oxaliplatin. Samples were then collected for tandem mass tag (TMT) labeling, high-performance liquid chromatography fractionation, and MS-based quantitative proteomics for analysis The differentially expressed proteins were quantitatively compared and identified, and Gene Ontology (GO) assessment and cluster analyses were performed. Finally, the above MS results were verified again by Western blotting experiments. Results: A total of 349 differentially expressed proteins were identified between cells treated with chemotherapy alone (group B) and cells treated with a combination of chemotherapy and hyperthermia (group D). There were 145 upregulated proteins and 204 downregulated proteins. Among the top 20 proteins with significantly different expression levels, nearly two-thirds were involved in DNA damage repair. These proteins were subsequently verified by Western blot analysis. Indeed, consistent with MS data, the expression of the RBL1 protein was significantly upregulated in cells treated with thermochemotherapy (group D) compared to cells treated with chemotherapy alone (group B). Conclusions: In heat-sensitive ovarian cancer cells, the damage repair of tumor cell DNA is disturbed by hyperthermia, making it unable to fully repair when damaged by chemotherapeutic drugs. As a result, hyperthermia enhances the efficacy of chemotherapeutic drugs. RBL1, as a tumor suppressor gene, may be associated with the repair of DNA damage, and thus it may be a key target for hyperthermia to enhance the sensitivity of thermosensitive cells to chemotherapeutic drugs.

Telitacicept following plasma exchange in the treatment of subjects with recurrent neuromyelitis optica spectrum disorders: A single-center, single-arm, open-label study.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD), mainly mediated by B cells and AQP4 antibody, has a high rate of recurrence. Telitacicept is a novel drug specifically targeting the upstream signaling for the activation of B cell with its following production of autoimmune antibodies. Thus, it may be a promising approach. Our study preliminarily explored the potential safety and effectiveness of Telitacicept following plasma exchange in the treatment of recurrent NMOSD. METHODS: This was a single-center, single-arm, open-label study enrolling eight patients with recurrent NMOSD in China. All patients received plasma exchange three times, followed by Telitacicept 240 mg every week for 46 times. The primary endpoint was the time of first recurrence after enrollment. Secondary end points included: changes in Expanded Disability Status Scale score, Optic Spinal Impairment Scale score, Hauser Ambulation Index, number of lesions on MRI, retinal nerve fiber layer thickness measured by optical coherence tomography, latency and amplitude of visual evoked potential, titer of AQP4 antibody, and immune parameters of blood. Safety was also assessed. The study was registered with Chictr.org.cn (ChiCTR1800019427). RESULTS: Eight eligible patients were enrolled. Relapse occurred in two patients (25%) and five patients (63%) remained relapse free after 48 weeks of treatment. The time to first recurrence was prolonged and the number of recurrences was reduced (p < 0.001, power of test = 1). One patient withdrew from the study due to low neutrophil count. No serious adverse events occurred. CONCLUSIONS: In this small, uncontrolled study, Telitacicept following plasma exchange has the potential to be a safe treatment for patients with recurrent NMOSD. It may prolong the recurrence interval and reduces the annual count of recurrences. A multicenter randomized controlled study with a larger sample is thus feasible and needed to further assess its safety and efficacy.

Human Umbilical Cord Mesenchymal Stem Cells to Treat Neuromyelitis Optica Spectrum Disorder (hUC-MSC-NMOSD): A Study Protocol for a Prospective, Multicenter, Randomized, Placebo-Controlled Clinical Trial.

Background: Neuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating NMOSD. Methods: The trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC-MSCs. Patients will be treated with three different doses of hUC-MSCs: 1, 2, or 5 × 106 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years. Discussion: Although hUC-MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC-MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC-MSC in treating NMOSD and might be able to determine the optimal dose of hUC-MSC for NMOSD patients. Trial registration: The study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.

Gender-specific association between non-alcoholic fatty liver disease and type 2 diabetes mellitus among a middle-aged and elderly Chinese population: An observational study.

ABSTRACT: Limited data are available regarding the association of non-alcoholic fatty liver disease (NAFLD) with the risk of type 2 diabetes mellitus (T2DM) in China. Therefore, the purpose of this study is to evaluate the gender-specific association between NAFLD and T2DM risk in a middle-aged and elderly Chinese population.This cross-sectional study was carried out in a group of 1492 Chinese adults (60.30% males) aged between 45 and 69 years old, in Hangzhou city, Zhejiang province who were attending their annual health check-up from June 2015 to December 2016 in the Medical Center for Physical Examination, Zhejiang Hospital. Face-to-face interviews were conducted using a written questionnaire. NAFLD was divided into none, mild, moderate/severe based on ultrasound examination. Logistic regression analyses were employed to determine the relationship between NAFLD and the risk of T2DM, with adjustment of potential confounding variables.Of the 1492 participants, 163 (10.92%) were diagnosed with T2DM. Educational level, smoking, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose (FG), triglycerides (TG), alanine aminotransferase (ALT), asparagine aminotransferase (AST)and the prevalence of T2DM were significantly higher in males than in females (P < .05). Besides, females had significantly higher levels of high density lipoprotein-cholesterol (HDL-C) (1.51 ±â€Š0.37 vs 1.29 ±â€Š0.42, P < .001) than males. Pearson bivariate correlation analysis indicated that FG was positively associated with weight, BMI, WC, WHR, SBP, DBP, TG, TC, ALT and AST in both males and females (P < .05). Besides, FG was inversely associated with HDL-C in females (P < .001). After adjusting for confounding variables, NAFLD was positively associated with the risk of T2DM, and the effect of NAFLD on T2DM was stronger in males (OR = 2.442, 95%CI: 1.003-3.757) than in females (OR = 1.814, 95%CI: 1.011-3.257).Our data showed that NAFLD was significantly associated with the risk of T2DM in middle-aged and elderly males than in females. Further prospective cohort studies are needed to determine the causal effect of NAFLD on T2DM.

Effect of comprehensive care on the negative emotions and life quality in parturients with postpartum depression and gestational hypertension.

OBJECTIVE: To investigate the efficacy of comprehensive care during the nursing process of parturients with gestational hypertension and postpartum depression. METHODS: This prospective study recruited 70 patients with gestational hypertension concurrent with postpartum depression, and the patients were randomly divided into a control group (35 patients received routine care) and an observation group (35 patients, treated by comprehensive care). Indicators including psychological condition, life quality, thyroid function, the incidence of eclampsia, and nursing satisfaction were recorded and compared before intervention (at the diagnosis of postpartum depression) and after intervention (three months after delivery) in the two groups. RESULTS: The Hamilton Anxiety (HAMA) Scale and Hamilton Depression (HAMD) Scale scores were decreased in both groups after care intervention. Scores of Quality of Life Comprehensive Assessment Questionnaire (GQOLI-74) in all dimensions were higher after intervention than those of before intervention, and improvement was greater in the observation group (P<0.05). The levels of thyroid-stimulating hormone, free triiodothyronine and free thyroxine after the intervention were higher than those before the intervention in the two groups, and the increase in the observation group was greater significant than that in the control group (P<0.05). The incidence of postpartum eclampsia in the observation group was lower than that of the control group, and the nursing satisfaction of patients in the observation group was higher than that of the control group (both P<0.05). CONCLUSION: Comprehensive care effectively relieved the abnormal psychological condition, promoted thyroid function, reduced the risk of postpartum eclampsia and improved the quality of life in patients with gestational hypertension and postpartum depression.

Egg consumption and risk of type 2 diabetes mellitus in middle and elderly Chinese population: An observational study.

Data on the association between egg consumption and the risk of type 2 diabetes mellitus (T2DM) in the Chinese population are scarce. In the present study, we aimed to examine the association between egg consumption and the risk of T2DM in a middle and elderly Chinese population. A total of 3298 subjects (1645 men and 1653 women) from the Nutrition and Health Survey (2015-2017) in Hangzhou city were selected for the final analysis. Egg consumption was assessed using a validated food frequency questionnaire. All biochemical data and anthropometric measurements were collected following standardized procedures. Multivariable logistic regression analyses were used to assess the association between egg consumption and the risk of T2DM and the results were presented as odds ratios and 95% confidence interval (CI). Restricted cubic spline combined with logistic regression was used to explore the dose-response relationship between egg consumption and T2DM. Among 3298 subjects, 693 (21.0%) people had T2DM. Compared with participants who did not consume egg per week, the multivariable-adjusted odds ratios were 0.97 (95%CI : 0.78-1.21), 1.08 (95%CI : 0.91-1.06), 1.20 (95%CI : 0.94-1.55), 1.27 (95%CI : 0.99-1.68) in men (P > .05); 1.06 (95%CI : 0.81-1.37), 0.97 (95%CI : 0.78-1.21), 1.26 (95%CI : 0.99-1.59), 1.19 (0.92-1.54) in women (P > .05); 0.89 (95%CI : 0.79-1.04), 0.98 (95%CI : 0.91-1.06), 1.06 (95%CI : 0.87-1.30), 1.09 (95%CI : 0.88-1.34) in both men and women for egg consumption 0∼7, 7, 7∼14, and ≥14 eggs/week, respectively (P > .05). The dose-response curve showed that, with the increase of egg consumption, the risk of T2DM first increased and then decreased (P = .027).We found that the association between egg consumption and T2DM was nonlinear, and higher egg consumption was not associated with an elevated risk for T2DM in middle-aged and elderly Chinese. However, future prospective studies are needed to confirm these findings.

Supramolecular self-assembly of three-dimensional polyaniline and polypyrrole crystals.

Herein, we first report a novel approach for preparing 3D π-π stacked crystals of polyaniline and polypyrrole and show how they self-assemble in a suitable solution environment. 3D crystals of polyaniline and polypyrrole show high charge-transport properties of 130 S cm(-1) and 150 S cm(-1), respectively. Remarkably, the 3D crystals of polyaniline obtain excellent anisotropic conductivity.

[Photosynthetic characteristics and coenological survey of Lactuca serriola in its invaded area].

Lactuca serriola, a national class quarantine object, is a new invasive species in the coastal area of Southeast China. The coenological survey showed that because of its big individual, L. serriola could easily form dominant population in its invaded area, and its main accompany species were Conyza canadensis, C. bonarinisis, Bidentis bipinnata, Oenothera laciniata, Ipomoea hederacea, Setaria viridis, Daucus carota, Xanthium sibiricum, Erigeron annuus, L. indica, Humulus scandens, Solanum nigrum and Aster sublatus. The measurements with LCA-4 portable photosynthesis and transpiration system (ADC, England) revealed that the net photosynthetic rate of L. serriola was as high as 21.22 +/- 0.45 micromol CO2 x m(-2) x s(-1), being slightly lower than that of E. annuus and C. bonarinisis, similar to that of C. canadensis, and higher than that of Chenopodium album, Plantago virginica and L. indica. Based on the photosynthesis-light response equation, the theoretic light compensation point of L. serriola was 37.58 micromol m(-2) x s(-1), its theoretic light saturation point was 1 480 micromol x m(-2) x s(-1), and theoretic maximal net photosynthetic rate was 20.81 micromol CO2 x m(-2) x s(-1). A distinct "noon break" phenomenon was observed in L. serriola photosynthesis, which might result from the high stomatal resistance against high light intensity and temperature. The main factors affecting the net photosynthetic rate of L. serriola were leaf photosynthetic active radiation, stomatal conductance, and leaf transpiration rate.