Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

ObjectiveTo explore the mechanisms of Salviae Miltiorrhizae Radix et Rhizoma in treating metabolic hypertension induced by a high-sugar and high-fat diet in rats based on network pharmacology， proteomics， and animal experiments. MethodsThirty male SD rats were randomized into the control， model， positive drug （tetrandrine， Tet， 50 mg·kg^-1·d^-1）， low-dose Salviae Miltiorrhizae Radix et Rhizoma （DS-L， 45×10⁴ mg·kg^-1·d^-1）， and high-dose Salviae Miltiorrhizae Radix et Rhizoma （DS-H， 90×10⁴ mg·kg^-1·d^-1） groups. Except for the control group， each group was fed a high-fat and high-sugar diet for 8 weeks for the modeling of metabolic hypertension. Following successful modeling， drug interventions were conducted through gavage for 4 weeks. Blood pressure and lipid indicators were monitored， and cardiac function was assessed via echocardiography. Samples from the thoracic aorta and cardiac tissue were collected for histopathological examination. Network pharmacology analysis identified key active components， potential targets， and mechanisms of Salviae Miltiorrhizae Radix et Rhizoma in treating hypertension. Proteomics technology was employed to analyze the differential proteins and major pathway targets to synergistically elucidate the antihypertensive mechanism of Salviae Miltiorrhizae Radix et Rhizoma. Ca²⁺ concentrations in the thoracic aorta and cardiac tissue were measured. The protein levels of transient receptor potential cation channel （TRPC）3， TRPC6， NADPH oxidase （NOX）2， and NOX4 were quantified via Western blotting. The levels of oxidative stress markers and inflammatory factors， including superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β）， were determined by enzyme-linked immunosorbent assay （ELISA）. Molecular docking analysis was performed for the main components of Salviae Miltiorrhizae Radix et Rhizoma with TRPC3， TRPC6， NOX2， and NOX4. ResultsThe experimental results indicated that compared with the control group， the model group exhibited abnormally elevated blood pressure and increased lipid levels （P<0.01）. Compared with the model group， the DS-L group exhibited reduced systolic blood pressure （SBP）， diastolic blood pressure （DBP）， and mean arterial pressure （MAP） （P<0.05）， decreased serum levels of triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05）， and increased level of high-density lipoprotein cholesterol （HDL-C） （P<0.01）. The DS-H and Tet groups showed more significant effects （P<0.01）. Moreover， the interventions attenuated vascular wall thickening， myocardial cell injury， and collagen and lipid deposition. Network pharmacology and proteomics prediction results indicated that the core targets of Salviae Miltiorrhizae Radix et Rhizoma in treating hypertension were TRPC3， TRPC6， NOX2， and NOX4， and the core pathways included calcium signaling， cyclic guanosine monophosphate （cGMP）/cGMP-dependent protein kinase （PKG） signaling， and atherosclerosis-related pathways. The molecular mechanism experiment results indicated that compared with the control group， the model group exhibited significantly elevated tissue Ca²⁺ concentrations， exacerbated oxidative stress and inflammatory responses， and upregulated protein levels of TRPC3， TRPC6， NOX2， and NOX4 in the thoracic aorta and myocardial tissue （P<0.01）. Compared with the model group， DS-L reduced the free Ca²⁺ concentration， lowered the levels of IL-1β， TNF-α， SOD， and MDA （P<0.05）， and downregulated the protein levels of TRPC3， TRPC6， NOX2， and NOX4 in the thoracic aorta and myocardial tissue （P<0.05）. DS-H and Tet exhibited more significant effects （P<0.01）. Meanwhile， the main components of Salviae Miltiorrhizae Radix et Rhizoma had strong binding affinity with the core targets of hypertension. ConclusionSalviae Miltiorrhizae Radix et Rhizoma may ameliorate oxidative stress and mitigate inflammatory responses by regulating the TRPC3/6/NOX2/4 signaling pathway， thereby alleviating abnormal blood pressure abnormality and myocardial injury in hypertensive rats.

Background Diarrhea disease is a common intestinal infectious disease, and its incidence is affected by meteorological conditions. A better understanding of its epidemiological patterns and influencing factors, together with the construction of reliable prediction models, is of great significance for precise public health prevention and control. Objective To clarify the epidemic characteristics of adult diarrhea disease in Shanghai, analyze the associations of meteorological factors and a web search index with adult diarrhea disease, and develop and compare forecasting models to support precise regional prevention and control. Methods Weekly surveillance data of adult diarrhea disease cases from the Shanghai Comprehensive Surveillance Information System for Diarrhea Diseases, together with concurrent meteorological observation data and web search index (Baidu index) data from 2014 to 2019, were collected. A distributed lag non-linear model (DLNM) was adopted to analyze the associations of multiple meteorological factors and the web search index with the number of diarrhea disease cases. By integrating meteorological factors and web search index data, three types of forecasting models were developed, including autoregressive integrated moving average (ARIMA), Random Forest, and extreme gradient boosting (Xgboost), and their predictive performances were evaluated. Results Adult diarrhea disease in Shanghai exhibited seasonal variation, with an major incidence peak in summer and winter peaks in some years. The number of cases declined annually after 2015. Mean temperature was significantly associated with the risk of diarrhea disease, and both low and high temperature exposures were associated with increased risks. The highest risk was observed at 32.8°C (RR=2.04, 95%CI: 1.62, 2.55), while the strongest effect of low temperature was observed at 0.9 °C (RR=1.53, 95%CI: 1.25, 1.88). When relative humidity exceeded 69%, the risk of diarrhea disease increased with relative humidity, reaching a peak at 81% (RR=1.20, 95%CI: 1.07, 1.35). When weekly cumulative precipitation exceeded 16 mm, the risk also increased with increasing precipitation, reaching a maximum at 105 mm (RR=1.23, 95%CI: 1.07, 1.42). The web search index was positively associated with the risk of diarrhea disease. Model prediction indicated that both the Random Forest model and the Xgboost model adequately captured the overall trend in diarrhea disease cases, with R² values generally exceeding 0.7. Notably, the Xgboost model demonstrated greater accuracy in capturing peak intensities. Conclusion Meteorological factors are associated with adult diarrhea disease in Shanghai. The web search index may serve as an auxiliary indicator for diarrhea forecasting. Machine learning models, with advantages in integrating multisource data, may provide effective predictive tools for the prevention and control of diarrhea disease.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a common digestive system disease with high prevalence and recurrence rates for years， high treatment costs， and serious impacts on patients' quality of life and economic burden. Therefore， it is important to explore new and safe treatment methods. The pathogenesis of IBS-D is complex， in which the gut-brain axis is a key factor. The gut-brain axis， a bidirectional signaling pathway connecting the gastrointestinal tract and the central nervous system， regulates gastrointestinal motility， secretion， and immune responses， playing a key role in the occurrence and development of IBS-D. Up to now， antidiarrheal agents， probiotics， and neurotransmitter modulators are the main methods for the clinical treatment of IBS-D. Although they can partially curb the progression of this disease， the therapeutic effects remain to be improved. Studies have confirmed that traditional Chinese medicine （TCM） has significant advantages in the treatment of IBS-D since it can regulate the gut-brain axis via multiple pathways and targets to improve the gastrointestinal motility and strengthen immune defenses. However， there is a lack of systematic reviews on the regulation of the gut-brain axis by TCM in the treatment of IBS-D. Based on the review of IBS-D-related articles published in recent years， this paper systematically summarized the relationship between the gut-brain axis and IBS-D and the role of TCM in the treatment， providing new ideas for the treatment of IBS-D.

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

BACKGROUND:Osteoporotic fracture is the most serious complication of osteoporosis.Previous studies have demonstrated that gut microbiota has a regulatory effect on skeletal tissue and that gut microbiota has an important relationship with osteoporotic fracture,but the causal relationship between the two is unclear. OBJECTIVE:To explore the causal relationship between gut microbiota and osteoporotic fractures using Mendelian randomization method. METHODS:The genome-wide association study(GWAS)datasets of gut microbiota and osteoporotic fracture were obtained from the IEU Open GWAS database and the Finnish database R9,respectively.Using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,Mendelian randomization analyses with random-effects inverse variance weighted,MR-Egger regression,weighted median,simple model,and weighted model methods were performed to assess whether there is a causal relationship between gut microbiota and osteoporotic fracture.Sensitivity analyses were performed to test the reliability and robustness of the results.Reverse Mendelian randomization analyses were performed to further validate the causal relationship identified in the forward Mendelian randomization analyses. RESULTS AND CONCLUSION:The results of this Mendelian randomization analysis indicated a causal relationship between gut microbiota and osteoporotic fracture.Elevated abundance of Actinomycetales[odds ratio(OR)=1.562,95%confidence interval(CI):1.027-2.375,P=0.037),Actinomycetaceae(OR=1.561,95%CI:1.027-2.374,P=0.037),Actinomyces(OR=1.544,95%CI:1.130-2.110,P=0.006),Butyricicoccus(OR=1.781,95%CI:1.194-2.657,P=0.005),Coprococcus 2(OR=1.550,95%CI:1.068-2.251,P=0.021),Family ⅩⅢ UCG-001(OR=1.473,95%CI:1.001-2.168,P=0.049),Methanobrevibacter(OR=1.274,95%CI:1.001-1.621,P=0.049),and Roseburia(OR=1.429,95%CI:1.015-2.013,P=0.041)would increase the risk of osteoporotic fractures in patients.Elevated abundance of Bacteroidia(OR=0.660,95%CI:0.455-0.959,P=0.029),Bacteroidales(OR=0.660,95%CI:0.455-0.959,P=0.029),Christensenellacea(OR=0.725,95%CI:0.529-0.995,P=0.047),Ruminococcaceae(OR=0.643,95%CI:0.443-0.933,P=0.020),Enterorhabdus(OR=0.558,95%CI:0.395-0.788,P=0.001),Eubacterium rectale group(OR=0.631,95%CI:0.435-0.916,P=0.016),Lachnospiraceae UCG008(OR=0.738,95%CI:0.546-0.998,P=0.048),and Ruminiclostridium 9(OR=0.492,95%CI:0.324-0.746,P=0.001)would reduce the risk of osteoporotic fractures in patients.We identified 16 gut microbiota associated with osteoporotic fracture by the Mendelian randomization method.That is,using gut microbiota as the exposure factor and osteoporotic fracture as the outcome variable,eight gut microbiota showed positive causal associations with osteoporotic fracture and another eight gut microbiota showed negative causal associations with osteoporotic fracture.The results of this study not only identify new biomarkers for the early prediction of osteoporotic fracture and potential therapeutic targets in clinical practice,but also provide an experimental basis and theoretical basis for the study of improving the occurrence and prognosis of osteoporotic fracture through gut microbiota in bone tissue engineering.

BACKGROUND:The causal relationship between modifiable factors such as lifestyle,metabolic characteristics,and nutritional intake and joint sports injuries has been increasingly recognized in clinical studies.However,the exact causal relationship between these modifiable factors and joint sports injuries remains unclear. OBJECTIVE:To investigate the causal relationship between modifiable factors and joint sports injuries using Mendelian randomization to provide a basis for sports injury prevention. METHODS:The GWAS dataset of intervening factors and joint sports injuries was obtained from publicly available data.The causal relationships between lifestyle,metabolic characteristics,nutritional intake,and joint sports injuries were explored using the inverse variance weighting method,the MR-Egger method,and the weighted median method.For sensitivity analyses,Cochran's Q test,MR-Egger regression,leave-one-out method,and MR-PRESSO were used to verify the stability and reliability of the results. RESULTS AND CONCLUSION:(1)In terms of lifestyle,coffee(OR=0.29,95%CI:0.10-0.79,P=0.016),and tea consumption(OR=0.41,95%CI=0.19-0.85,P=0.017)were associated with a decreased risk of ankle and foot joint sports injuries,and coffee consumption(OR=3.31,95%CI=1.02-10.73,P=0.046)was potentially causally associated with an increased risk of shoulder joint sports injuries;and never smoking(OR=0.78,95%CI=0.70-0.87,P=1.49×10-5)was significantly causally associated with a decreased risk of ankle and foot joint sports injuries.(2)In terms of metabolic characteristics,calcium levels(OR=0.88,95%CI=0.79-0.98,P=0.017)were potentially causally associated with a decreased risk of wrist and hand joint sports injuries.(3)In terms of nutritional intake,vitamin A intake(OR=1.08,95%CI:1.02-1.13,P=0.007)was potentially causally associated with increased risk of knee joint sports injury.(4)For the sensitivity analysis,Cochran's Q test showed the existence of heterogeneity(P<0.05),so the random effect model was used for the analysis.MR-Egger regression and MR-PRESSO test did not find evidence of pleiotropy(P>0.05),and the leave-one-out method showed that the results were stable after eliminating single nucleotide polymorphisms one by one.(5)This study preliminarily reveals the effects of modifiable factors,such as lifestyle,metabolic characteristics,and nutritional intake,on the risk of joint sports injuries.It provides valuable research evidence and guidance for the prevention of joint sports injuries.