Discovery of a potent inhibitor, D-132, targeting AsfvPolX, via protein-DNA complex-guided pharmacophore screening and in vitro molecular characterizations.

The heightened transmissibility and capacity of African swine fever virus (ASFV) induce fatal diseases in domestic pigs and wild boars, posing significant economic repercussions and global threats. Despite extensive research efforts, the development of potent vaccines or treatments for ASFV remains a persistent challenge. Recently, inhibiting the AsfvPolX, a key DNA repair enzyme, emerges as a feasible strategy to disrupt viral replication and control ASFV infections. In this study, a comprehensive approach involving pharmacophore-based inhibitor screening, coupled with biochemical and biophysical analyses, were implemented to identify, characterize, and validate potential inhibitors targeting AsfvPolX. The constructed pharmacophore model, Phar-PolX-S, demonstrated efficacy in identifying a potent inhibitor, D-132 (IC50 = 2.8 ± 0.2 µM), disrupting the formation of the AsfvPolX-DNA complex. Notably, D-132 exhibited strong binding to AsfvPolX (KD = 6.9 ± 2.2 µM) through a slow-on-fast-off binding mechanism. Employing molecular modeling, it was elucidated that D-132 predominantly binds in-between the palm and finger domains of AsfvPolX, with crucial residues (R42, N48, Q98, E100, F102, and F116) identified as hotspots for structure-based inhibitor optimization. Distinctively characterized by a 1,2,5,6-tetrathiocane with modifications at the 3 and 8 positions involving ethanesulfonates, D-132 holds considerable promise as a lead compound for the development of innovative agents to combat ASFV infections.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

Evaluation of compliance of CONSORT-CHM formula 2017 in randomized controlled trials of Chinese herbal medicine formulas: protocol of a five-year review.

Background: The CONSORT Extension for Chinese Herbal Medicine Formula 2017 (CONSORT-CHM Formula 2017) has established a reporting standard for randomized controlled trials (RCTs) of Chinese Herbal Medicine Formula (CHMF) interventions; however, its adherence and implications for the design and execution of study design remain ambiguous. It is necessary to evaluate the level of compliance with the CONSORT-CHM Formula 2017 in RCTs conducted over the past 5 years, and to determine the reporting quality of clinical trials in this field. Methods: First, a systematic search is conducted for RCTs on CHMF in EBM Reviews, Allied and Complementary Medicine (AMED), Embase, Ovid-MEDLINE(R), Wanfang data, China National Knowledge Infrastructure (CNKI), VIP Chinese Medical Journal Database (VIP) and Chinese Biomedical Literature (CBM) database, that encompassed CHMF interventional RCTs published from 1 January 2018 to 8 June 2022, with language restriction to English or Chinese. Second, a descriptive analysis will be performed regarding the study design and general characteristics of the included trials. Third, for the quality assessment, we have subdivided the CONSORT-CHM Formula 2017 checklist (consisting of 22 extended items) into a total of 42 sub-questions to facilitate scoring, with a specific focus on the description, quality control, and safety assessment of CHMF interventions. Professional training and a pilot test on 100 randomly selected articles will be provided for all reviewers. Throughout this process, a standard operating procedure (SOP) for quality assessment will be developed to ensure consistency. Each item will be assessed by two reviewers in a paired back-to-back manner, and the compliance rate will be calculated to assess inter-rater agreement. Discussion: This review will identify the current reporting characteristics and quality of CHMF interventional studies and further evaluate the impact of CONSORT-CHM Formula 2017. The results may provide suggestions for future application or promotion of the guideline. Registration: The study has been registered on Open Science Framework (https://osf.io/xpn7f).

Yin Yang 1 expression predicts a favourable survival in diffuse large B-cell lymphoma.

Aims: Yin Yang 1 (YY1) is a multifunctional transcription factor that plays an important role in tumour development and progression, while its clinical significance in diffuse large B-cell lymphoma (DLBCL) remains largely unexplored. This study aimed to investigate the expression and clinical implications of YY1 in DLBCL. Methods: YY1 expression in 198 cases of DLBCL was determined using immunohistochemistry. The correlation between YY1 expression and clinicopathological parameters as well as the overall survival (OS) and progression-free survival (PFS) of patients was analyzed. Results: YY1 protein expression was observed in 121 out of 198 (61.1 %) DLBCL cases. YY1 expression was significantly more frequent in cases of the GCB subgroup than in the non-GCB subgroup (P = 0.005). YY1 was positively correlated with the expression of MUM1, BCL6, pAKT and MYC/BCL2 but was negatively associated with the expression of CXCR4. No significant relationships were identified between YY1 and clinical characteristics, including age, sex, stage, localization, and B symptoms. Univariate analysis showed that the OS (P = 0.003) and PFS (P = 0.005) of patients in the YY1-negative group were significantly worse than those in the YY1-positive group. Multivariate analysis indicated that negative YY1 was a risk factor for inferior OS (P < 0.001) and PFS (P = 0.017) independent of the international prognostic index (IPI) score, treatment and Ann Arbor stage. Furthermore, YY1 is more powerful for stratifying DLBCL patients into different risk groups when combined with MYC/BCL2 double-expression (DE) status. Conclusions: YY1 was frequently expressed in DLBCL, especially in those of GCB phenotype and with MYC/BCL2-DE. As an independent prognostic factor, YY1 expression could predict a favourable outcome in DLBCL. In addition, a complex regulatory mechanism might be involved in the interactions between YY1 and MYC, pAKT as well as CXCR4 in DLBCL, which warrants further investigation.

[Role of macrophage polarization in hypertension and traditional Chinese medicine intervention: a review].

Hypertension is known to be a chronic inflammatory state and a key risk factor for heart failure, coronary heart disease, and atherosclerosis. Macrophages in the circulatory system are the main cell group that constitutes the immune system and participates in the inflammatory response. Depending on the local microenvironment, macrophages can be polarized into pro-inflammatory(M1) and anti-inflammatory(M2) phenotypes. When blood pressure is elevated, M1 macrophages can release pro-inflammatory cytokines and chemokines to generate an immune response. However, an excessive immune response can lead to tissue damage, and M2 macrophages release anti-inflammatory cytokines to promote the repair of wounds and tissue damage. It is clear that the dynamic balance between M1 and M2 macrophages resembles the traditional Chinese medicine(TCM) theory of Yin and Yang. That is, when Yin and Yang are imbalanced, the human body will exhibit pathological states, e.g., altered blood pressure rhythms. Studies have confirmed that TCM can produce positive therapeutic effects on hypertension by regulating macrophage polarization. Therefore, this study reviews the studies about the TCM regulation of macrophage polarization and summarized the mechanisms of TCM intervention in hypertension, with the aim of providing evidence for clinical treatment and ideas for scientific research design.

Alleviation of allergic asthma by rosmarinic acid via gut-lung axis.

BACKGROUND: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. PURPOSE: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. METHODS: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. RESULTS: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. CONCLUSIONS: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.

Predictive Model Construction And Prevention Strategies Of Surgical Site Infection In Laparoscopic Appendectomy.

Objective: To construct a nomogram model for predicting the occurrence of the laparoscopic appendectomy surgical site infection (LASSI) and explore prevention strategies. Methods: A total of 995 patients who underwent laparoscopic appendectomy in Shanxi Bethune Hospital from October 2017 to August 2022 were selected. According to whether there was incision infection within 30 days after operation, the patients were divided into the LASSI (97 cases) and non-LASSI (898 cases) group. The following clinicopathological data from these two groups of patients were collected: gender, age, body mass index, ect. The subjects were randomly divided into training group and verification group according to the 7:3 ratio. Univariate and multivariate analysis was used to screen the related influencing factors and construct a nomogram model to predict the occurrence of LASSI. Rreceiver operating characteristic (ROC) curves and the calibration curve were used to evaluate the predictive value of the model. For patients with LASSI, a more effective preventive measure was explored. Results: Multivariate logistic regression analysis showed that operation time >1h (OR: 1.891; 95% CI: 1.07 to 3.36; P = .029), perforated and gangrenous appendix (OR: 4.078; 95% CI: 1.84 to 9.86; P = .001), free intraperitoneal fluid (OR: 2.836; 95% CI: 1.57 to 5.35; P = .001), BMI>30 kg/m2 (OR: 2.828; 95% CI:1.54 to 5.12; P = .001), diabetes mellitus (DM) (OR: 2.795; 95% CI: 1.54 to 5.28; P = .001) were the independent prognostic factors of LASSI. The prediction nomogram model showed satisfactory performance in predicting the occurrence of LASSI, ROC curve area value of the training and verification groups were respectively 0.753 (95 % CI: 0.688 ~ 0.818) and 0.772 (95 % CI: 0.691-0.852). In the event of LASSI, we took out appendix specimens in sections and sterilized surgical site, which effectively prevented it. Conclusion: This study evaluated the risk factors related to the occurrence of LASSI and established a prediction model for LASSI. The prediction model provides a convenient and fast risk assessment tool for clinicians to predict the occurrence of LASSI. Combined with the newly discovered prevention strategy of segmental removal of appendix and incision disinfection, it can effectively avoid the occurrence of LASSI and potentially reduce the hospitalization time and costs.

Study on the Digestive Behavior of Chlorogenic Acid in Biomimetic Dietary Fiber and the Antioxidative Synergistic Effect of Polysaccharides and Chlorogenic Acid.

Chlorogenic acid (CA) is often combined with dietary fiber polysaccharides in plant foods, which may affect its digestive behavior and antioxidant activity. This study constructed a biomimetic dietary fiber (BDF) model by combining bacterial cellulose (BC) and pectin with CA and investigated the digestive behavior of CA in BDF. Additionally, the study examined the interaction and synergistic effects of polysaccharides and CA against oxidation. Results showed that BDF and natural dietary fiber had similar microstructures, group properties, and crystallization properties, and polysaccharides in BDF were bound to CA. After simulated gastrointestinal digestion, 41.03% of the CA existed in a conjugated form, and it was possibly influenced by the interaction between polysaccharides and CA. And the release of CA during simulated digestion potentially involved four mechanisms, including the disintegration of polysaccharide-CA complex, the dissolution of pectin, escape from BC-pectin (BCP) network structure, and diffusion release. And polysaccharides and CA may be combined through noncovalent interactions such as hydrogen bonding, van der Waals force, or electrostatic interaction force. Meanwhile, polysaccharides-CA combination had a synergistic antioxidant effect by the results of free-radical scavenging experiments, it was probably related to the interaction between polysaccharides and CA. The completion of this work has a positive significance for the development of dietary intervention strategies for oxidative damage.

One-lung Ventilation for Patients With Laryngo-tracheal Stenosis: A Case Report and Literature Review.

Context: Laryngo-tracheal stenosis (LTS) is a relatively rare disease, and conventional methods have difficulty achieving one-lung ventilation (OLV) when an anatomical abnormality exists. Selecting an appropriate method for patients with LTS can ensure oxygenation, collapse the lung, and reduce damage. Objective: The study intended to perform a comprehensive review of the literature and a systematic review to examine the characteristics and management of OLV for LTS patients. Design: The research team performed a narrative review by searching the PubMed and China National Knowledge Infrastructure (CNKI) databases. The search used the keywords one-lung ventilation and tracheal stenosis. The team then performed a review, including the studies found in the search and the research team's own case study. Setting: The study took place at the First Hospital of Jilin University in Changchun, Jilin, China. Participant: The participant in the current case study was a 72-year-old, female patient with generalized tracheal narrowing. Results: Nine participants achieved OLV through BB, with the anesthesiologist performing SLT and using extraluminal BB for six participants. Conclusions: Several methods can successfully achieve OLV for patients with difficult airways, but the current research team found that a small, single-lumen tube (SLT) and extraluminal bronchial blocker (BB) may be a better choice for patients with tracheal stenosis.

[Potential targets for traditional Chinese medicine treatment of chronic inflammation in obesity: macrophage polarization].

Obesity has been identified as a chronic low-grade systemic inflammation and a key risk factor for diseases such as diabetes, hypertension, and malignancies, and has become an urgent global health burden. Adipose tissue macrophages play a significant role in adipose immune homeostasis and inflammatory responses. Under different conditions, they can be polarized into pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype. In obese individuals, there is abnormal polarization of macrophages in adipose tissue, leading to an imbalance in the M1/M2 phenotype dynamic equilibrium and the development of pathological inflammation. Therefore, restoring the balance of M1/M2 macrophage polarization is an important potential target for the treatment of chronic inflammation in obesity. Studies have shown that traditional Chinese medicine(TCM) can positively modulate macrophage polarization and produce beneficial effects on obesity. Based on existing evidence, this paper systematically reviewed the potential mechanisms of TCM in improving chronic inflammation in obesity from the perspective of macrophage polarization, in order to provide evidence for the clinical diagnosis and treatment of chronic inflammation in obesity with TCM and offer new insights for related research design and the development of new TCM.

Global research trends and hotspots of Helicobacter pylori eradication based on clinical trial registration platforms: A cross-sectional analysis.

BACKGROUND: This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS: We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS: A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION: How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.

Co-inoculation of phosphate-solubilizing bacteria and phosphate accumulating bacteria in phosphorus-enriched composting regulates phosphorus transformation by facilitating polyphosphate formation.

This study aimed to explore the impact of co-inoculating phosphate-solubilizing bacteria (PSB) and phosphate accumulating bacteria (PAB) on phosphorus forms transformation, microbial biomass phosphorus (MBP) and polyphosphate (Poly-P) accumulation, bacterial community composition in composting, using high throughput sequencing, PICRUSt 2, network analysis, structural equation model (SEM) and random forest (RF) analysis. The results demonstrated PSB-PAB co-inoculation (T1) reduced Olsen-P content (1.4 g) but had higher levels of MBP (74.2 mg/kg) and Poly-P (419 A.U.) compared to PSB-only (T0). The mantel test revealed a significantly positive correlation between bacterial diversity and both bioavailable P and MBP. Halocella was identified as a key genus related to Poly-P synthesis by network analysis. SEM and RF analysis showed that pH and bacterial community had the most influence on Poly-P synthesis, and PICRUSt 2 analysis revealed inoculation of PAB increased ppk gene abundance in T1. Thus, PSB-PAB co-inoculation provides a new idea for phosphorus management.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and the Risk of Incident Rosacea: Insights from Mendelian Randomization and Cohort Study in the UK Biobank.

BACKGROUND: Previous cross-sectional studies have failed to definitively establish a causal relationship between serum 25-hydroxyvitamin D (25OHD) concentrations and the onset of rosacea. OBJECTIVE: To investigate the potential association between serum 25OHD levels, vitamin D receptor (VDR) polymorphisms, and the risk of developing incident rosacea. METHODS: This cross-sectional population-based cohort study utilizing 370,209 individuals from the UK Biobank. Cox proportional hazard regression models and two-sample Mendelian randomization (MR) analyses were applied to explore the causative relationship between 25OHD and incident rosacea. RESULTS: Our findings revealed that elevated levels of serum 25OHD were inversely correlated with the risk of incident rosacea. Specifically, compared to participants with 25OHD levels below 25 nmol/L, the multivariate-adjusted HR for incident rosacea was 0.81 (95% CI: 0.70, 0.94) in those with 25OHD levels exceeding 50 nmol/L. Further, in comparison to individuals with serum 25OHD less than 25 nmol/L and the rs731236 (TaqI) AA allele, those with serum 25OHD higher than 75 nmol/L and the TaqI GG allele had a multivariate-adjusted HR of 0.51 (95% CI 0.32 to 0.81) for developing rosacea. Results from the MR study supported a significant association, with each standard deviation increase in serum 25OHD concentrations correlating to a 23% reduced risk of rosacea (HR = 0.77, 95% CI: 0.63, 0.93). CONCLUSIONS: The findings of this cohort study indicate an inverse association between increased concentrations of serum 25OHD and the risk of developing incident rosacea. While our results highlight the potential protective role of vitamin D, the definitive efficacy of vitamin D supplementation as a preventive strategy against rosacea requires further investigation.

Co-assembled Supramolecular Hydrogel of Salvianolic Acid B and a Phosphopeptide for Enhanced Wound Healing.

Supramolecular natural product gels (NPGs) have emerged as promising biomaterials for scalable and adjustable drug delivery systems. These gels possess biocompatibility, biodegradability, and the ability to mimic the extracellular matrix. Salvianolic acid B (SAB), derived from Salvia miltiorrhiza, a Chinese medicinal plant, exhibits various beneficial properties such as antioxidant, antifibrotic, and angiogenic effects. In our research, we serendipitously discovered that the co-assembly of SAB and a soluble phosphopeptide results in the formation of a robust and adhesive hydrogel termed 1&SAB hydrogel. This hydrogel effectively prolongs the retention time of the therapeutic agents on the skin's wound surface, thereby promoting wound healing. The hydrogel demonstrates antioxidant effects, enhances cell migration, accelerates angiogenesis, and inhibits scar hyperplasia. This innovative gel material offers a simple and efficient approach to managing skin wounds and holds promise for application in complex wound-healing treatments.

Could long-term dialysis vintage and abnormal calcium, phosphorus and iPTH control accelerate aging among the maintenance hemodialysis population?

OBJECTIVE: Aging is a complex process of physiological dysregulation of the body system and is common in hemodialysis patients. However, limited studies have investigated the links between dialysis vintage, calcium, phosphorus, and iPTH control and aging. The purpose of the current study was to examine these associations. METHODS: During 2020, a cross-sectional study was conducted in 3025 hemodialysis patients from 27 centers in Anhui Province, China. Biological age was calculated by a formula using chronological age and clinical indicators. The absence of the target range for serum phosphorus (0.87-1.45 mmol/L), corrected calcium (2.1-2.5 mmol/L) and iPTH (130-585 pg/mL) were identified as abnormal calcium, phosphorus, and iPTH control. RESULTS: A total of 1131 hemodialysis patients were included, 59.2% of whom were males (669/1131). The mean (standard deviation) of actual age and biological age were 56.07 (12.79) years and 66.94 (25.88), respectively. The median of dialysis vintage was 4.3 years. After adjusting for the confounders, linear regression models showed patients with abnormal calcium, phosphorus, and iPTH control and on hemodialysis for less than 4.3 years (B = 0.211, p = .002) or on hemodialysis for 4.3 years or more (B = 0.302, p < .001), patients with normal calcium, phosphorus, and iPTH control and on hemodialysis for 4.3 years or more (B = 0.087, p = .013) had a higher biological age. CONCLUSION: Our findings support the hypothesis that long-term hemodialysis and abnormal calcium, phosphorus, and iPTH control may accelerate aging in the hemodialysis population. Further studies are warrant to verify the significance of maintaining normal calcium-phosphorus metabolism in aging.

Apigenin inhibits macrophage pyroptosis through regulation of oxidative stress and the NF-κB pathway and ameliorates atherosclerosis.

Pyroptosis plays an important role in inflammatory diseases such as viral hepatitis and atherosclerosis. Apigenin exhibits various bioactivities, particularly anti-inflammation, but its effect on pyroptosis remains unclear. The aim of this study is to investigate the effect of apigenin on pyroptosis and explore its potential against inflammatory diseases. THP-1 macrophages treated by lipopolysaccharides/adenosine 5'-triphosphate were used as the in vitro pyroptosis model. Western blot was used to detect the expression of NLRP3 inflammasome components and key regulators. Immunofluorescence was used to observe ROS production and intracellular location of p65. The potential of apigenin against inflammatory diseases was evaluated using atherosclerotic mice. Plaque progression was observed by pathological staining. Immunofluorescence was used to observe the expression of NLRP3 inflammasome components in plaques. The results showed that apigenin inhibited NLRP3 inflammasome activation. Apigenin reduced ROS overproduction and inhibited p65 nuclear translocation. Additionally, apigenin decreased the expression of NLRP3 inflammasome components in the plaque. Plaque progression was inhibited by apigenin. In conclusion, apigenin exhibited a preventive effect on macrophage pyroptosis by reducing oxidative stress and inhibiting the NF-κB pathway. Apigenin may alleviate atherosclerosis at least partially by inhibiting macrophage pyroptosis. These findings suggest apigenin to be a promising therapeutic agent for inflammatory diseases.

[Network Meta-analysis of Qi-supplementing and Yin-nourishing Chinese patent medicines in treatment of early diabetic nephropathy].

This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.

Concurrent chemoradiotherapy followed by adjuvant cisplatin-gemcitabine versus cisplatin-fluorouracil chemotherapy for N2-3 nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Patients with N2-3 nasopharyngeal carcinoma have a high risk of treatment being unsuccessful despite the current practice of using a concurrent adjuvant cisplatin-fluorouracil regimen. We aimed to compare the efficacy and safety of concurrent adjuvant cisplatin-gemcitabine with cisplatin-fluorouracil in N2-3 nasopharyngeal carcinoma. METHODS: We conducted an open-label, randomised, controlled, phase 3 trial at four cancer centres in China. Eligible patients were aged 18-65 years with untreated, non-keratinising, stage T1-4 N2-3 M0 nasopharyngeal carcinoma, an Eastern Cooperative Oncology Group performance status score of 0-1, and adequate bone marrow, liver, and renal function. Eligible patients were randomly assigned (1:1) to receive concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 of intensity-modulated radiotherapy followed by either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 3 weeks or fluorouracil (4 g/m2 in continuous intravenous infusion for 96 h) and cisplatin (80 mg/m2 intravenously for 4 h on day 1) once every 4 weeks, for three cycles. Randomisation was done using a computer-generated random number code with a block size of six, stratified by treatment centre and nodal category. The primary endpoint was 3-year progression-free survival in the intention-to-treat population (ie, all patients randomly assigned to treatment). Safety was assessed in all participants who received at least one dose of chemoradiotherapy. This study was registered at ClinicalTrials.gov, NCT03321539, and patients are currently under follow-up. FINDINGS: From Oct 30, 2017, to July 9, 2020, 240 patients (median age 44 years [IQR 36-52]; 175 [73%] male and 65 [27%] female) were randomly assigned to the cisplatin-fluorouracil group (n=120) or cisplatin-gemcitabine group (n=120). As of data cutoff (Dec 25, 2022), median follow-up was 40 months (IQR 32-48). 3-year progression-free survival was 83·9% (95% CI 75·9-89·4; 19 disease progressions and 11 deaths) in the cisplatin-gemcitabine group and 71·5% (62·5-78·7; 34 disease progressions and seven deaths) in the cisplatin-fluorouracil group (stratified hazard ratio 0·54 [95% CI 0·32-0·93]; log rank p=0·023). The most common grade 3 or worse adverse events that occurred during treatment were leukopenia (61 [52%] of 117 in the cisplatin-gemcitabine group vs 34 [29%] of 116 in the cisplatin-fluorouracil group; p=0·00039), neutropenia (37 [32%] vs 19 [16%]; p=0·010), and mucositis (27 [23%] vs 32 [28%]; p=0·43). The most common grade 3 or worse late adverse event (occurring from 3 months after completion of radiotherapy) was auditory or hearing loss (six [5%] vs ten [9%]). One (1%) patient in the cisplatin-gemcitabine group died due to treatment-related complications (septic shock caused by neutropenic infection). No patients in the cisplatin-fluorouracil group had treatment-related deaths. INTERPRETATION: Our findings suggest that concurrent adjuvant cisplatin-gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2-3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Major Project of Basic and Applied Basic Research, Sci-Tech Project Foundation of Guangzhou City, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Guangdong Province for Distinguished Young Scholar, Natural Science Foundation of Guangdong Province, Postdoctoral Innovative Talent Support Program, Pearl River S&T Nova Program of Guangzhou, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, the Rural Science and Technology Commissioner Program of Guangdong Province, and Fundamental Research Funds for the Central Universities.

Research status and prospects of acupuncture for autism spectrum disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder and has a predilection for children. Its symptoms, such as lifelong social communication deficits and repetitive sensory-motor behaviors, put a huge burden on the patient's family and society. Currently, there is no cure for ASD, and some medications that can improve its symptoms are often accompanied by adverse effects. Among many complementary and alternative medicine (CAM) therapies, acupuncture has shown promising application potential, but after years of practice, it has not been recognized as the preferred CAM therapy for ASD. Therefore, we analyzed and discussed the clinical study reports of acupuncture in the treatment of ASD in the past 15 years from the aspects of study subjects, group setting, intervention modalities, acupoint selection, outcome evaluation, and safety. The data accumulated at present are not sufficient to support the clinical effectiveness of acupuncture in ASD and to justify its use in clinical practice. They provide, however, initial evidence of possible effectiveness and encourage further investigation in order to reach firm conclusions. Based on a comprehensive analysis, we believed that following the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) and Consolidated Standards of Reporting Trials (CONSORT), screening the optimal combination of acupoints applying a rigorous scientific study design, and performing the related functional experiments may be the effective way to convincingly test the hypothesis that acupuncture may be beneficial in ASD patients. The significance of this review is to provide a reference for researchers to carry out high-quality clinical trials of acupuncture in the treatment of ASD from the perspective of the combination of modern medicine and traditional Chinese medicine.

Reporting quality of randomized controlled trials of angina pectoris with integrated traditional Chinese and western medicine interventions: a cross-sectional study.

BACKGROUND AND OBJECTIVE: Integrated traditional Chinese and western medicine (ITCWM), as a representative type of complex intervention, is commonly used for the treatment of angina pectoris (AP) in clinical practice. However, it is unclear whether the details of ITCWM interventions, such as rationale for selection and design, implementation and potential interactions for different therapies, were adequately reported. Therefore, this study aimed to describe the reporting characteristics and quality in randomized controlled trials (RCTs) of AP with ITCWM interventions. METHODS: Through a search of 7 electronic databases, we identified RCTs of AP with ITCWM interventions published in both English and Chinese from 1st Jan 2017 to 6th Aug 2022. The general characteristics of included studies were summarized, further, the quality of reporting was assessed based on three Checklists, including the CONSORT with 36 items (except for one item 1b about abstract), the CONSORT for abstracts (17 items), and a self-designed ITCWM-related checklist (21 items covering rationale and details of interventions, outcome assessment and analysis). The quality of RCTs published in English and Chinese, as well as journals and dissertations were also compared. RESULTS: A total of 451 eligible RCTs were included. For the reporting compliance, the mean score (95% Confidence Interval) of the CONSORT (72 scores in total), CONSORT for abstract (34 scores in total), and ITCWM-related (42 scores in total) checklists was 27.82 (27.44-28.19), 14.17 (13.98-14.37) and 21.06 (20.69-21.43), respectively. More than half items were evaluated as poor quality (reporting rate < 50%) among each Checklist. Moreover, the reporting quality of publications in English journals was higher than that in Chinese journals in terms of the CONSORT items. The reporting of published dissertations was better than that in journal publications regarding both the CONSORT and ITCWM-specific items. CONCLUSION: Although the CONSORT appears to have enhanced the reporting of RCTs in AP, the quality of ITCWM specifics is variable and in need of improvement. Reporting guideline of the ITCWM recommendations should be developed thus to improve their quality.