Endoplasmic Reticulum-Targeting Self-Assembly Nanosheets Promote Autophagy and Regulate Immunosuppressive Tumor Microenvironment for Efficient Photodynamic Immunotherapy.

The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP-TER-Zn@RSV nanosheets (TZR NSs) that co-assembled from the endoplasmic reticulum (ER)-targeting photosensitizer TCPP-TER-Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine-(2, 3)-dioxygenase (IDO) inhibitor-like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER-targeting TZR NSs developed in this paper presents a simple but valuable reference for high-efficiency tumor photodynamic immunotherapy.

Inhibition of autophagy enhances the anticancer effect of Schisandrin B on head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is among the most common malignant tumors worldwide and has a poor prognosis. Autophagy regulation has been proposed as a possible treatment option for HNSCC. Schisandrin B (Sch B) exerts anticancer effects by regulating apoptosis and autophagy, but the anticancer effect of Sch B in HNSCC remains unclear. This study aimed to investigate the effects of Sch B on human Cal27 HNSCC cells and to further reveal its potential regulatory mechanisms. The anticancer effect of Sch B was evaluated in vitro by flow cytometry, clonogenic assays, and Western blot analysis. The regulatory mechanism of Sch B-induced apoptosis and autophagy was further explored by polymerase chain reaction, luciferase assay, and reactive oxygen species (ROS) detection. The results showed that Sch B significantly induced apoptosis and autophagy in Cal27 cells and that inhibition of autophagy enhanced the apoptotic effect of Sch B on Cal27 cells. Additionally, Sch B-activated autophagy in Cal27 cells was dependent on the nuclear factor-kappa B (NF-κB) pathway, and ROS acted as a regulator of the NF-B pathway. N-acetylcysteine, a scavenger of ROS, inhibited Sch B-dependent autophagy via the NF-κB pathway. Based on the results, Sch B is a potential therapeutic agent for HNSCC and activates the NF-κB pathway by increasing ROS production, which subsequently promotes autophagy in HNSCC cells. Therefore, the strategy of enhancing the anticancer effect of Sch B by inhibiting autophagy deserves further attention.

Manganese-derived biomaterials for tumor diagnosis and therapy.

Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials with applications across diverse fields, particularly in tumor diagnosis and therapy. Systematic reviews specifically addressing the tumor diagnosis and therapy aspects of Mn-derived biomaterials are lacking. This review comprehensively explores the physicochemical characteristics and synthesis methods of Mn-derived biomaterials, emphasizing their role in tumor diagnostics, including magnetic resonance imaging, photoacoustic and photothermal imaging, ultrasound imaging, multimodal imaging, and biodetection. Moreover, the advantages of Mn-based materials in tumor treatment applications are discussed, including drug delivery, tumor microenvironment regulation, synergistic photothermal, photodynamic, and chemodynamic therapies, tumor immunotherapy, and imaging-guided therapy. The review concludes by providing insights into the current landscape and future directions for Mn-driven advancements in the field, serving as a comprehensive resource for researchers and clinicians.

Comparative Effectiveness of Team-Based Care With and Without a Clinical Decision Support System for Diabetes Management : A Cluster Randomized Trial.

BACKGROUND: Uncontrolled hyperglycemia, hypercholesterolemia, and hypertension are common in persons with diabetes. OBJECTIVE: To compare the effectiveness of team-based care with and without a clinical decision support system (CDSS) in controlling glycemia, lipids, and blood pressure (BP) among patients with type 2 diabetes. DESIGN: Cluster randomized trial. (ClinicalTrials.gov: NCT02835287). SETTING: 38 community health centers in Xiamen, China. PATIENTS: 11 132 persons aged 50 years or older with uncontrolled diabetes and comorbid conditions, 5475 receiving team-based care with a CDSS and 5657 receiving team-based care alone. INTERVENTION: Team-based care was delivered by primary care physicians, health coaches, and diabetes specialists in all centers. In addition, a computerized CDSS, which generated individualized treatment recommendations based on clinical guidelines, was implemented in 19 centers delivering team-based care with a CDSS. MEASUREMENTS: Coprimary outcomes were mean reductions in hemoglobin A1c (HbA1c) level, low-density lipoprotein cholesterol (LDL-C) level, and systolic BP over 18 months and the proportion of participants with all 3 risk factors controlled at 18 months. RESULTS: During the 18-month intervention, HbA1c levels, LDL-C levels, and systolic BP significantly decreased by -0.9 percentage point (95% CI, -0.9 to -0.8 percentage point), -0.49 mmol/L (CI, -0.53 to -0.45 mmol/L) (-19.0 mg/dL [CI, -20.4 to -17.5 mg/dL]), and -9.1 mm Hg (CI, -9.9 to -8.3 mm Hg), respectively, in team-based care with a CDSS and by -0.6 percentage point (CI, -0.7 to -0.5 percentage point), -0.32 mmol/L (CI, -0.35 to -0.29 mmol/L) (-12.5 mg/dL [CI, -13.6 to -11.3 mg/dL]), and -7.5 mm Hg (CI, -8.4 to -6.6 mm Hg), respectively, in team-based care alone. Net differences were -0.2 percentage point (CI, -0.3 to -0.1 percentage point) for HbA1c level, -0.17 mmol/L (CI, -0.21 to -0.12 mmol/L) (-6.5 mg/dL [CI, -8.3 to -4.6 mg/dL]) for LDL-C level, and -1.5 mm Hg (CI, -2.8 to -0.3 mm Hg) for systolic BP. The proportion of patients with controlled HbA1c, LDL-C, and systolic BP was 16.9% (CI, 15.7% to 18.2%) in team-based care with a CDSS and 13.0% (CI, 11.7% to 14.3%) in team-based care alone. LIMITATION: There was no usual care control, and clinical outcome assessors were unblinded; the analysis did not account for multiple comparisons. CONCLUSION: Compared with team-based care alone, team-based care with a CDSS significantly reduced cardiovascular risk factors in patients with diabetes, but the effect was modest. PRIMARY FUNDING SOURCE: Xiamen Municipal Health Commission.

Effects of oropharyngeal exercises on CPAP compliance: A prospective intervention study.

PURPOSE: To investigate the effects of oropharyngeal exercise on continuous positive airway pressure (CPAP) compliance in patients with moderate to severe obstructive sleep apnea over a period of 6 months. MATERIALS AND METHODS: This study was conducted as a prospective, observational, and interventional investigation. A total of 70 patients with moderate to severe obstructive sleep apnea were randomly assigned to either the oropharyngeal exercise group (n = 44) or the sham-therapy group (n = 26). The compliance of the enrolled patients with CPAP therapy was assessed at baseline, 3-month follow-up and 6-month follow-up. Objective sleep data, questionnaire and CPAP use time were collected over a half-year period (i.e., baseline, 6 months, and 12 months). RESULTS: The study found that the average use time of CPAP within one month was significantly longer in the oropharyngeal exercises group compared to the sham-therapy group at the 3-month assessment (5.5 ± 1.2 vs 4.8 ± 1.3 h per night; p=0.030), and much significantly longer at 6-months assessment (6.0 ± 1.4 vs 4.9 ± 1.3 h per night; p=0.001). Furthermore, the average use time of CPAP increased over time, with the oropharyngeal exercises group exhibiting a more pronounced growth from baseline to the six-month follow-up (4.8 ± 1.0 h per night to 6.0 ± 1.3 h per night, p < 0.001) compared to the sham-therapy group (4.8 ± 1.3 h per night to 4.9 ± 1.3 h per night, p=0.952). Additionally, the oropharyngeal exercise group demonstrated an improvement in the Epworth sleepiness scale compared to the sham-therapy group at the 3-month follow-up (6.0 ± 2.0 vs 8.8 ± 3.2; p < 0.001), as well as decreased significantly at 6-month follow-up (p = 0.032). CONCLUSIONS: CPAP adherence can be improved with oropharyngeal exercises therapy among moderate to severe OSA patients. Notably, the average duration of CPAP usage and reduction in daytime sleepiness were maintained even after six months of oropharyngeal exercise therapy.

P66Shc is increased in peripheral blood mononuclear cells of the patients with obstructive sleep apnea.

Objective: Obstructive sleep apnea (OSA) is characterized by nocturnal intermittent hypoxemia and linked to oxidative stress. Evidence demonstrated that p66Shc plays a key role in regulating oxidative stress. This study aimed to investigate the expression of p66Shc in peripheral blood mononuclear cells (PBMCs) of patients with OSA and the association with polysomnographic parameters. Methods: Fifty-four OSA subjects and 19 no OSA controls were enrolled in this study. All the subjects underwent standard polysomnography. P66Shc mRNA and protein levels in the PBMCs were detected by quantitative real-time polymerase chain reaction and western blotting. Plasma 3-nitrotyrosine (3-NT), oxidized low density lipoprotein (oxLDL), and advanced oxidation protein products (AOPP) were measured by ELISA method. Results: P66Shc mRNA and protein levels in PBMCs were significantly higher in OSA patients than in controls. P66Shc mRNA was positively correlated with plasma 3-NT, oxLDL, AOPP, hypopnea index (AHI), oxygen desaturation index (ODI), percentage of total sleep time with oxygen saturation (SaO2) below 90% (CT90), epworth sleepiness scale (ESS) and lymphocytes; negatively correlated with lowest SaO2 (LSaO2) and mean SaO2 (MSaO2). Further multivariate linear regression analysis showed that p66Shc mRNA levels were independently associated with AHI, MSaO2 and CT90. Conclusions: Oxidative stress regulator p66Shc may play a role in the pathophysiology of OSA and might serve as a potential biomarker for this disease.

Esketamine Combined with Propofol TCI versus Propofol TCI for Deep Sedation during Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: A Prospective, Randomized, and Controlled Trial.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an invasive procedure that required deep sedation to suppress coughing and body movements. Deep sedation, on the other hand, has been shown to cause respiratory and circulatory depression, especially when the airway is shared with the endoscopist. Esketamine is a novel sedative and analgesic with little respiratory inhibition that appears to be an appropriate adjuvant in propofol sedation for EBUS-TBNA. We compared the efficacy and safety of esketamine combined with propofol target-controlled infusion (TCI) and propofol TCI for deep sedation in EBUS-TBNA. Methods: The study included 135 patients with ASA II-III undergoing EBUS-TBNA. They were randomly divided into two groups (group E and group P). Both groups received midazolam (0.01-0.03 mg/kg) and oxycodone (0.07-0.08 mg/kg). Then, patients in group E received 0.3 mg/kg esketamine, propofol TCI, and 0.2 mg·kg-1·h-1 esketamine for sedative maintenance. Patients in group P received only propofol TCI. The primary outcome was the dose of 1% lidocaine administrated by the endoscopist and the times of lidocaine sprays. Secondary outcome indicators were cough score, propofol dosage, patient satisfaction, endoscopist satisfaction, the incidence of sedation-related adverse effects and side effects, and recovery time. Results: Patients in group E were given significantly less lidocaine (4.36 ml/h (2.67-6.00) vs 6.00 ml/h (4.36-7.20), P < 0.001) and less spraying frequency (2.18 times/h (1.33-3.00) vs 3.00 times/h (2.18-3.60), P < 0.001) than group P. There was a statistically significant difference in cough score between the two groups (group E 2 (0-4) vs group P 3 (2-4), P=0.03). Also, mean arterial pressure (MAP) was higher in group E in the 30th min (T5, 84.10 ± 12.91 mmHg versus 79.04 ± 10.01 mmHg, P=0.012) and 40th min (T6, 87.72 ± 15.55 mmHg versus 82.14 ± 10.51 mmHg, P=0.026). There were no significant differences between the two groups in terms of sedation-related adverse events and side effects, recovery time, endoscopist satisfaction, and patient satisfaction. Conclusions: In patients with ASA II-III, esketamine as an adjuvant in combination with propofol TCI deep sedation for EBUS-TBNA can improve the sedation effect, reduce coughing reaction during the procedure, and obtain more stable blood pressure. No reduction in the occurrence of sedation-related side effects was observed. This trial is registered with ChiCTR2200061124.

Age-specific effects on adverse pregnancy outcomes vary by maternal characteristics: a population-based retrospective study in Xiamen, China.

BACKGROUND: Advanced maternal age (AMA; ≥35 years) is considered to be a major risk factor for adverse pregnancy outcomes. Along with the global trend of delayed childbearing, and in particular, the implementation of China's second and third-child policy leading to a dramatic increase of AMA in recent years, the association between maternal age and pregnancy outcomes requires more investigation. METHODS: A population-based retrospective study was performed. Data were derived from the Medical Birth Registry of Xiamen from 2011 to 2018. Univariate and multivariate logistic regression was used to evaluate the effects of maternal age on pregnancy outcomes. RESULTS: A total of 63,137 women categorized into different age groups (< 25 years, 25-29 years, 30-34 years, and ≥ 35 years) were included in this study. Compared with the mothers aged 25-29 years, the univariate regression analysis showed that mothers aged < 25 years had lower risks of gestational diabetes mellitus (GDM) and cesarean. AMA was associated with higher risks of GDM, hypertension, cesarean, preterm birth, low-birth weight (LBW), large-for-gestational-age (LGA), macrosomia, and stillbirth (all P < 0.01). After adjustment for potential confounding factors, increased risks of GDM, hypertension, cesarean, preterm birth, and LBW remained significantly associated with AMA (all P < 0.05), whereas AMA mothers showed a lower risk of macrosomia than their younger counterparts. Additionally, no significant differences were detected in terms of Apgar score < 7. CONCLUSION: AMA was associated with adverse pregnancy outcomes including increased risks of GDM, hypertension, cesarean, preterm birth, and LBW. This study confirmed the relationship between AMA and certain adverse maternal and fetal outcomes and emphasizes the necessity for women to be cautious about the age at which they become pregnant.

Circ_0000523 regulates miR-1184/COL1A1/PI3K/Akt pathway to promote nasopharyngeal carcinoma progression.

BACKGROUND: The present study is to investigate the biological functions and mechanisms of circular RNA_0000523 (circ_0000523) in nasopharyngeal carcinoma (NPC). METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to examine the expression levels of circ_0000523 and microRNA-1184 (miR-1184) in NPC tissues and cells. Collagen type 1 alpha 1 chain (COL1A1) expression was assessed by qRT-PCR and immunohistochemistry (IHC) assay. Cell proliferation, cell cycle progression, migration and invasion were examined by cell counting kit-8 (CCK-8), 5-bromo-2'-deoxyuridine (BrdU), flow cytometry and Transwell assays. Xenograft nude mouse models were used to investigate the metastatic potential of NPC cells in vivo. The binding relationships between circ_0000523 and miR-1184, and between miR-1184 and COL1A1 were detected by dual-luciferase reporter gene assay. The protein expressions of COL1A1, phosphatidylinositol 3-kinase (p85), phosphorylated (p)-p85, protein kinase B (Akt) and p-Akt were detected through Western blot. The DAVID database was used for the enrichment analysis of the potential targets of miR-1184. RESULTS: Circ_0000523 and COL1A1 mRNA expressions were significantly increased in NPC tissues and cell lines. Circ_0000523 overexpression promoted NPC cell proliferation and accelerated cell cycle progression, whereas miR-1184 overexpression reversed these effects; circ_0000523 knockdown suppressed NPC cell proliferation and induced cell cycle arrest, while miR-1184 inhibition counteracted these effects. MiR-1184 was the downstream target of circ_0000523, and COL1A1 was the target gene of miR-1184 and could be positively modulated by circ_0000523. COL1A1 overexpression increased the expression levels of p-p85 and p-Akt, whereas knocking down COL1A1 repressed their expressions. CONCLUSIONS: Circ_0000523 facilitates NPC progression through regulating the miR-1184/COL1A1 axis.

The correlation between triiodothyronine and the severity of liver fibrosis.

BACKGROUND: The severity of liver fibrosis is an important predictor of death in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). However, there is still no definite conclusion on the relationship between triiodothyronine (T3) and the severity of liver fibrosis. Thus, the aim of this study was to analyze the correlation between T3 level and the severity of liver fibrosis. METHODS: We performed a cross-sectional study of 2072 T2DM patients with normal thyroid function from January 2017 to January 2020. NAFLD fibrosis score (NFS), Fibrosis index based on the 4 factors (FIB-4) and BARD score (BARD) were used to assess the severity of fibrosis in T2DM patients, and linear regression analyses were used to determine the factors independently associated with liver fibrosis. Further experiments were performed to assess the impact of low T3 on fibrosis progression in mice model and explore possible mechanisms. RESULTS: Free triiodothyronine (fT3) levels had significantly inverse correlations with NFS and FIB-4, and BARD in T2DM patients (P < 0.05). In multiple linear regression analyses, decreased fT3 level was an independent risk factor for the severity of liver fibrosis of T2DM patients (P < 0.01). Findings from in-vivo experiment using mice model proved that hypothyroidism mice had more severe of liver fibrosis than those mice with normal thyroid function. We also found that T3 could inhibit the profibrotic TREM2+CD9+ macrophage, which had been identified an important player in the progression of liver fibrosis. CONCLUSION: The findings from this study proved an inverse correlation between T3 level and the severity of liver fibrosis, and lower fT3 level within the normal range was an independent risk factor for severe liver fibrosis.

Diagnostic value of Lipoarabinomannan antigen for detecting Mycobacterium tuberculosis in adults and children with or without HIV infection.

OBJECTIVES: Even today, tuberculosis (TB) remains a leading public health problem; yet, the current diagnostic methods still have a few shortcomings. Lipoarabinomannan (LAM) provides an opportunity for TB diagnosis, and urine LAM detection seems to have a promising and widely applicable prospect. DESIGN OR METHODS: Four databases were systematically searched for eligible studies, and the quality of the studies was evaluated using the quality assessment of diagnostic accuracy studies-2 (QUADAS-2). Graphs and tables were created to show sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), the area under the curve (AUC), and so on. RESULTS: Based on the included 67 studies, the pooled sensitivity of urine LAM was 48% and specificity was 89%. In the subgroup analyses, the FujiLAM test had higher sensitivity (69%) and specificity (92%). Furthermore, among patients infected with human immunodeficiency virus (HIV), 50% of TB patients were diagnosed using a urine LAM test. Besides, the CD4+ cell count was inversely proportional to the sensitivity. CONCLUSIONS: Urine LAM is a promising diagnostic test for TB, particularly using the FujiLAM in HIV-infected adults whose CD4+ cell count is ≤100 per µl. Besides, the urine LAM test shows various sensitivities and specificities in different subgroups in terms of age, HIV infection status, CD4+ cell count, and testing method.

Comparative effectiveness of team-based care with a clinical decision support system versus team-based care alone on cardiovascular risk reduction among patients with diabetes: Rationale and design of the D4C trial.

BACKGROUND: Diabetes has become a major public health challenge worldwide, especially in low- and middle-income countries (LMICs). Uncontrolled hyperglycemia, hypertension, and dyslipidemia major risk factors for all-cause mortality and cardiovascular disease (CVD) are common in patients with diabetes in China. We propose to compare the effectiveness of team-based care plus a clinical decision support system (CDSS) with team-based care alone on glycemic, blood pressure (BP), and lipid control, and clinical CVD reduction among patients with type-2 diabetes and at high risk for CVD. METHODS: The Diabetes Complication Control in Community Clinics (D4C) study is a cluster-randomized trial conducted among 38 community health centers in Xiamen City, China. Nineteen clinics have been randomly assigned to team-based care plus CDSS and 19 to team-based care alone. Team-based care includes primary care providers, health coaches, and diabetes specialists working collaboratively with patients to achieve shared treatment goals for CVD risk factor reduction. The CDSS integrates guideline-based treatment algorithms for glycemic, BP, and lipid control, along with a patient's medical history and insurance policy, to recommend treatment and follow-up plans. In phase 1, the co-primary outcomes are mean reduction in glycated hemoglobin (HbA1c), systolic BP (SBP), and low-density lipoprotein (LDL)-cholesterol over 18 months, and the proportion of patients with controlled HbA1c, SBP, and LDL-cholesterol at 18 months' between the 2 comparison groups. In phase 2, the primary outcome is the difference in major CVD incidence (non-fatal stroke, non-fatal myocardial infarction, hospitalized heart failure, and CVD mortality) between the 2 comparison groups. Mean reduction in HbA1c, SBP, and LDL-cholesterol levels will be simultaneously modeled for a single overall treatment effect. CONCLUSION: The D4C trial will generate evidence on whether a CDSS will further reduce the CVD burden among patients with diabetes beyond team-based care at community clinics. If proven effective, this implementation strategy could be scaled up within primary care settings in China and other LMICs to reduce CVD incidence and mortality among patients with diabetes.

[Bayesian network Meta-analysis of traditional Chinese medicine injections combined with antiviral western medicine in treatment of influenza].

To systematically evaluate the efficacy and safety of traditional Chinese medicine injections combined with antiviral wes-tern medicine in the treatment of influenza by Bayesian network Meta-analysis. Four Chinese databases(CNKI, Wanfang, VIP, CBM) and three English databases(PubMed, EMbase, Cochrane Library) were retrieved by computer for randomized controlled trials(RCT) about the comparison between the combined administration of traditional Chinese medicine injections with antiviral western medicine(or with placebo) and the single administration of antiviral western medicine in the treatment of influenza, or the comparison between two different traditional Chinese medicine injections combined with antiviral western medicine in the treatment of influenza. The retrieval time was from the establishment of the databases to July 2020. Two researchers independently screen out the literatures and extracted the data according to the inclusion criteria and exclusion criteria. The included studies were evaluated by the Cochrane 5.1 bias risk assessment tool, and data analysis was conducted by ADDIS 1.16.8 and Stata 14.0. A total of 49 literatures about 5 061 cases were included finally, involving six traditional Chinese medicine injections, namely Reduning Injection, Xiyanping Injection, Tanreqing Injection, Yanhuning Injection, Qingkailing Injection and Shuanghuanglian Injection. The results of network Meta-analysis,(1)in terms of total effective rate, 6 traditional Chinese medicine injections combined with antiviral western medicine was better than antiviral western medicine alone. In terms of probability sorting, Shuanghuanglian Injection combined with antiviral western medicine ranked first.(2)There was no significant statistical difference in adverse reaction rate among all groups, but Reduning Injection ranked first in the probability sorting, due to the least side effects.(3)In terms of antipyretic time, Yanhuning Injection, Xiyanping Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Xiyanping Injection ranked first in the probability sorting.(4)In terms of cough relief time, Qingkailing Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Qingkailing Injection was superior to Yanhuning Injection. Qingkailing Injection combined with antiviral western medicine ranked first in the probability sorting.(5)In terms of the length of hospital stay, Xiyanping Injection, Tanreqing Injection and Reduning Injection combined with antiviral western medicine was superior to antiviral western medicine alone, and Reduning Injection ranked first in the probability sorting due to the shortest hospital stay. Because of the small quantity and low quality of included studies, the results of this study shall be regarded cautiously and comprehensively. In the future, multi-center, large-sample and clinical randomized controlled trials shall be conducted to verify the results.

MATERNAL GESTATIONAL DIABETES MELLITUS AND OFFSPRING BODY MASS INDEX FROM 1 TO 4 YEARS.

Objective: Using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria to diagnose gestational diabetes mellitus (GDM), the association between GDM and offspring body mass index (BMI) gains in early childhood in China remains unclear. We aimed to assess the association between GDM diagnosed by the IADPSG criteria and BMI gain and the risk for overweight/obesity in offspring from 1 to 4 years. Methods: This prospective cohort study was based on the healthcare records data from the Medical Birth Registry in Xiamen, China. We included 10,412 mother-child pairs tested for GDM using IADPSG criteria. Results: A total of 1,786 (17.2%) offspring were exposed to GDM. The offspring exposed to GDM had higher mean BMI Z-score (difference, 0.07; 95% confidence interval [CI], 0.02 to 0.12) and risk for overweight/obesity (odds ratio [OR], 1.22; 95% CI, 1.06 to 1.40) compared to those unexposed to GDM from 1 to 4 years of age. However, after adjustment for maternal pre-pregnancy BMI (Model 2), these associations attenuated towards the null (difference in BMI Z-score, 0.02; 95% CI, -0.03 to 0.07; OR for overweight/obesity, 1.09; 95% CI, 0.95 to 1.25). Conclusion: The associations between GDM diagnosed using IADPSG criteria and BMI Z-score and the risk for overweight/obesity in offspring at the age of 1 to 4 years were largely explained by maternal pre-pregnancy BMI. Reducing the prevalence of childhood overweight and obesity in China should focus on maternal weight status before pregnancy, in addition to glycemia during pregnancy. Abbreviations: BMI = body mass index; CI = confidence interval; GDM = gestational diabetes mellitus; IADPSG = International Association of Diabetes and Pregnancy Study Groups; LGA = large for gestational age; MBRX = Medical Birth Registry in Xiamen; OGTT = oral glucose tolerance test; OR = odds ratio.

Clinical significance of neuropilin-2 expression in laryngeal squamous cell carcinoma.

PURPOSE: The purpose of the study is to evaluate the expression of NRP-2 and explore its role in Laryngeal squamous cell carcinoma (LSCC). MATERIALS AND METHODS: NRP-2 expression in 70 primary LSCC tissue specimens were analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients´ survival rate. Additionally, 9 paired LSCC tissues were evaluated for NRP-2 expression by Western blotting. RESULTS: The Western blotting indicated that NRP-2 expression levels in LSCC were significantly higher than those in the paraneoplastic tissues (P < 0.05). Immunohistochemistry staining revealed that NRP-2 was detected in all primary tumor samples, moreover, high expression of NRP-2 was significantly correlated with TNM stage (P < 0.05), clinical stage (P < 0.05), histological classification (P < 0.05), lymph node metastasis (P < 0.05) and recurrence (P = 0.001). Survival curves determined by the Kaplan-Meier method showed that high expression of NRP-2 can reduce overall survival (both group P < 0.05). Then we combined the NRP-2 expression and lymph node status, and Kaplan-Meier survival showed patients with high expression of NRP-2 or lymph node metastasis (+) had both shorter disease-free and overall survival than others (both P < 0.05). Multivariate Cox proportional hazards model analysis confirmed that histological grade (P = 0.045), lymph node metastasis (P = 0.020) and high expression of NRP-2 (P = 0.033) were statistically significant, independent predictor of prognosis. CONCLUSIONS: NRP-2 may contribute to LSCC progression and represents as a novel prognostic indicator as well as a potential therapeutic target for LSCC.

Effects of Prepregnancy Body Mass Index, Weight Gain, and Gestational Diabetes Mellitus on Pregnancy Outcomes: A Population-Based Study in Xiamen, China, 2011-2018.

BACKGROUND: It is unclear that how prepregnancy body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM) affect pregnancy outcomes in -China. Thus, we explored how BMI, GWG, and GDM affect the risks of adverse pregnancy outcomes. METHODS: We performed a retrospective, population-based study included all births in Xiamen, China, 2011-2018. Demographic data and pregnancy outcomes of 73,498 women were acquired from the Medical Birth Registry of Xiamen. Women were categorized into groups on prepregnancy BMI and GWG in order to assess the risk of pregnancy outcomes. Multivariable logistic regression was performed to evaluate risk factors. RESULTS: Overall, 6,982 (9.37%) women were obese, and 8,874 (12.07%) women were overweight. Obese women are more vulnerable to cesarean delivery, preterm birth, large-for-gestational age (LGA), and macrosomia (crude OR [cOR] 2.00, 1.89-2.12; 1.35, 1.20-1.51; 2.12, 1.99-2.26; 2.53, 2.25-2.86, respectively, adjusted ORs 1.73, 1.62-1.84; 1.25, 1.10-1.42; 2.03, 1.90-2.18; 2.77, 2.44-3.16, respectively). Similar results were observed in overweight women (cORs 1.49, 1.42-1.57; 1.02, 0.91-1.15; 1.60, 1.50-1.70; 2.01, 1.78-2.26, respectively). Furthermore, women who gain weight in excessive group were 1.43, 2.06, and 2.16 times to deliver cesarean, LGA, and macrosomia, respectively. Additionally, GDM women were easily subjected to cesarean section, preterm birth, LGA, low birth weight, and macrosamia (cORs 1.52, 1.55, 1.52, 1.37, 1.27, respectively). CONCLUSIONS: Obesity prior to pregnancy, excessive GWG, and GDM were all associated with increased odds of cesarean, LGA, and macrosomia. Blood glucose and weight control before and during pregnancy are needed that may reduce the complications of pregnancy.

Elevated circulating irisin is associated with lower risk of insulin resistance: association and path analyses of obese Chinese adults.

BACKGROUND: Evidence on the role of irisin in insulin resistance is limited and controversial, and pathways between them remain unknown. We aimed to examine the independent effects of circulating irisin and different adiposity measurements, as well as their potential interactions, on insulin resistance. We also aimed to explore possible pathways among circulating irisin, adiposity, glucose and insulin levels and insulin resistance. METHODS: A cross-sectional study of 1,115 community- living obese Chinese adults, with data collection on clinical characteristics, glucose and lipid metabolic parameters and circulating irisin levels. RESULTS: Among the 1,115 subjects, 667 (59.8 %) were identified as insulin-resistance, and showed significantly decreased serum irisin than their controls (log-transformed irisin: 1.19 ± 2.34 v.s. 1.46 ± 2.05 ng/ml, p = 0.042). With adjustment for potential confounders, elevated circulating irisin was significantly associated with reduced risk of insulin resistance, with adjusted odds ratio per standard deviation increase of irisin of 0.871 (0.765-0.991, p = 0.036). As for different adiposity measurements, body fat percentage, but neither BMI nor waist, was significantly associated with increased risk of insulin resistance (OR: 1.152 (1.041-1.275), p = 0.006). No significant interaction effect between serum irisin and adiposity on insulin resistance was found. A one pathway model about the relationship between serum irisin and insulin resistance fits well (χ (2) = 44.09, p < 0.001; CFI-0.994; TLI =0.986; and RMSEA = 0.067), and shows that elevated circulating irisin might improve insulin resistance indirectly through lowering fasting insulin levels (standardized path coefficient = -0.046, p = 0.032). CONCLUSIONS: Elevated circulating irisin is associated with lower risk of insulin resistance indirectly through lowering fasting insulin.

Comparative efficacy of commercial oral poly-herbal traditional Chinese medicine formulations combined with western medicine in benign prostatic hyperplasia management: a systematic review and network meta-analysis.

Background: Benign prostatic hyperplasia (BPH) is prevalent among the aging male population and often presents with distressing lower urinary tract symptoms. There is emerging evidence that commercial oral poly-herbal traditional Chinese medicine (TCM) formulation combined with Western medicine (WM) may offer enhanced therapeutic effects compared to WM alone in BPH treatment. Nevertheless, determining the optimal formulations for BPH remains controversial. We aimed to employ a network meta-analysis to compare and assess differences among commonly used and recommended poly-herbal TCM formulations outlined in the Chinese guidelines for BPH treatment, providing clinical medication recommendations and guidance. Methods: We extensively searched for RCTs of BPH patients that had oral poly-herbal TCM formulations and WM treatment, covering both English and Chinese databases up to 31 October 2023. The quality of the included studies was evaluated using the Cochrane risk-of-bias tool Version 2 (ROB2). A Bayesian network meta-analysis was performed to assess the effectiveness of various formulations, followed by sensitivity and subgroup analyses. Results: Our meta-analysis included 107 RCTs involving 11,037 patients across 16 oral poly-herbal TCM formulations. The quality of the selected studies was assessed as "Some concerns". Most formulations combined with WM demonstrated superior therapeutic efficacy compared to WM alone. For clinical effective rate, Jingui Shenqi pill (JGSQ) + WM had the highest-ranking probability (87.38%). Concerning International Prostate Symptom Score (IPSS) and maximum flow rate of urine, Guizhi Fuling capsule (GZFL) + WM was most effective (91.10% and 98.55%). Regarding the quality of life score and postvoid residual urine, Pulean tablet (PLA) + WM ranked first (86.71% and 91.81%). In controlling prostate volume, Huange capsule (HE) + WM demonstrated the highest efficacy (95.65%). Additionally, among the interventions, Lingze (LZ) + WM capsule exhibited the lowest incidence of adverse drug reactions (2.32%). Conclusion: Combining oral poly-herbal TCM formulations with WM may provide greater therapeutic benefits in BPH treatment compared to WM alone. JGSQ, GZFL, PLA, and HE emerged as promising treatment options. However, further rigorous empirical studies are essential to substantiate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459651, CRD 42023459651.

Comprehensive effect of Naoxintong capsule combined with Western medicine on coronary heart disease after percutaneous coronary intervention: a meta-analysis.

Aims: To systematically evaluate the comprehensive effect of combining Naoxintong capsule (NXT) with Western medicine (WM) on coronary heart disease post-percutaneous coronary intervention (PCI). Methods: Randomized controlled trials (RCTs) of NXT for patients with CHD after PCI were systematically searched across multiple databases, including the Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP), and Wan Fang, from inception until 31 January 2023. Study selection, data extraction, and quality assessment were performed by two independent reviewers. The quality of the included studies was evaluated using version 2 of the Cochrane risk-of-bias tool (RoB 2), and data analysis was performed using R4.2.2. Results: Fifteen RCTs conducted between 2011 and 2022 and involving 1,551 patients were identified, with 774 and 777 patients in the experimental and control groups respectively. It was found that the NXT and WM combination was superior to the WM therapy alone in terms of the effective clinical rate (odds ratio [OR] = 4.69, 95% confidence interval [CI] = 2.13-10.30), effective rate in electrocardiogram (OR = 6.92, 95% CI = 3.44-13.92), effective rate in angina (OR = 5.90, 95% CI = 3.04-11.46), left ventricular ejection fraction (mean difference [MD] = 4.94, 95% CI = 2.89-6.99), brain natriuretic peptide (MD = -294.00, 95% CI = -584.60 to -3.39), creatine kinase-MB (MD = -7.82, 95% CI = -13.26 to -2.37), major adverse cardiovascular events (OR = 0.24, 95% CI = 0.14-0.43), maximum platelet aggregation rate (MD = -8.33, 95% CI = -11.64 to -5.01), and Chinese medicine evidence score (OR = 9.79, 95% CI = 3.57-26.85). However, there was no significant difference in cardiac troponin I level reduction (MD = -0.13, 95% CI = 0.35-0.09) or the occurrence of adverse medicine events (OR = 0.92, 95% CI = 0.41-2.05). Meta-regression and subgroup analyses indicated that NXT capsule dosage, treatment duration, and patient baseline characteristics contributed to the heterogeneity. Conclusion: A combination of NXT and WM can improve clinical outcomes in patients undergoing PCI. However, further studies are needed to confirm the reliability and safety of this combined treatment approach. Systematic Review Registration: PROSPERO, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=369174, Identifier CRD42022369174.

Molecular mechanism of the NOS/NOX regulation of antibacterial activity in Eriocheir sinensis.

To elucidate the role of nitric oxide synthase (NOS), which produces the free radical nitric oxide (NO), and nicotinamide adenine dinucleotide phosphate oxidase (NOX), which produces the superoxide anion (O2-), in the innate immunity of Eriocheir sinensis, the full lengths of the NOS and NOX genes were cloned via rapid amplification of the cDNA ends and then expressed in the prokaryotic form to obtain the recombinant proteins, NOS-HIS and NOX-HIS. Through bacterial binding and stimulation experiments, the molecular mechanisms of NOS and NOX in the innate immunity of E. sinensis were explored. Based on the results, NOS and NOX were 5900 bp and 4504 bp long, respectively, and were evolutionarily conserved. Quantitative real-time PCR revealed that NOS and NOX were expressed in all studied tissues, and both were expressed in the highest amounts in hemocytes. NOS-HIS and NOX-HIS could bind to bacteria with different binding powers; their binding ability to gram-positive bacteria was higher than that of binding to gram-negative bacteria. After stimulation with Aeromonas hydrophila, NOS expression was significantly up-regulated at 3, 6, and 48 h, and NOX expression was significantly down-regulated at 3, 12, 24, and 48 h. After bacterial stimulation, the NOS enzyme activity in the serum of E. sinensis was also significantly up-regulated at 6 and 48 h, and the NOX enzyme activity was significantly down-regulated at 12 and 48 h, aligning with the gene expression trend. Moreover, the related free radical molecules, NO, O2-, and H2O2, tended to decrease after bacterial stimulation. Overall, the gene expression and enzyme activity of NOS and NOX had been changed respectively, and the contents of a series of free radical molecules (NO, O2- and H2O2) were induced in E. sinensis after bacterial stimulation, which then exert antibacterial immunity.