OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

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.

OBJECTIVE To analyze the characteristics and influencing factors of disposal behavior of expired medicines among Chinese residents across regional divisions， and to provide references for regional classification management and precise policy implementation regarding expired medicines. METHODS A stratified random sampling method was employed to conduct a questionnaire survey among residents across sample provinces and cities， utilizing a combination of online and offline approaches. Binary Logistic regression analysis was used to systematically explore the regional （eastern， central and western regions） and urban-rural disparities in the recycling of expired medicines among Chinese residents， identify the core driving factors influencing standardized disposal behaviors， and propose corresponding recommendations. RESULTS A total of 2 200 ques tionnaires were collected， with 2 159 deemed valid， yielding an effective response rate of 98.1%. The surveyed residents commonly stored medicines at home （67.7%）， yet the rate of regular medicine clearance was low （only 57.7%）. Nearly half of the residents （49.7%） had expired medicines in their households， with improper disposal of expired medicines remaining the predominant behavior. Insufficient convenience in recycling was identified as the primary reason for improper disposal of expired medicines （50.1%）. Statistically significant differences were observed between residents in the eastern， central and western regions， as well as between urban and rural residents， in terms of household medicine storage rates and the prevalence of expired medicine possession （ P ＜0.05）. However， no statistically significant difference was found in the standardized disposal rates across regional divisions （ P ＞0.05）. Furthermore， the residents demonstrated a higher level of awareness regarding the health hazards of expired medicines compared to their awareness of environmental hazards， with 46.0% and 32.1% indicating they were “relatively familiar” and “very familiar”， respectively. The participation rate in standardized recycling was only 37.6%. Among non-participating residents， the three primary barriers were “recycling points being too far away” （46.6%）， “unawareness of recycling channels” （46.1%） and “lack of incentives” （48.1%）. The surveyed residents showed relatively high trust in pharmaceutical regulatory authorities and on-site recycling personnel， with “high trust” accounting for 31.2% and 34.7%， respectively. Binary Logistic regression analysis results indicated that the awareness of environmental hazards and the accessibility of recycling points were the core driving factors for proper disposal. CONCLUSIONS Significant issues exist in the recycling of expired medicines among Chinese residents， characterized by “improper behavior， cognitive bias， and unbalanced system”. It is recommended to construct a tiered recycling network focusing on “quality improvement in the eastern region， expansion in the central region， and basic coverage in the western region”， implement targeted educational campaigns and differentiated incentive policies. Moreover， the specific needs of groups such as the elderly should be addressed to achieve spatial equalization and service optimization of the recycling system.

ObjectiveThis paper aims to analyze the variety characteristics and prescription patterns of marketed traditional Chinese patent medicines for treating abortion and provide references for new medicine development and clinical application. MethodsRelevant information of traditional Chinese patent medicines for treating abortion was systematically retrieved and collected. Microsoft Excel 2021 software was used to sort and statistically analyze the medicine syndrome types， quantity， market situation， and status of package inserts. Based on the Ancient and Modern Medical Case Cloud Platform （V2.3.9）， the medicine properties， flavors， meridian tropism， and medication characteristics of standardized prescriptions were analyzed. ResultsA total of 39 marketed traditional Chinese patent medicines for treating abortion in China were included. According to disease type， these medicines were categorized as therapeutic medicines for threatened abortion and recurrent spontaneous abortion. According to clinical function， they were categorized into three groups： fetus stabilization， blood nourishment， and adjunctive conditioning. They were also categorized into pre-pregnancy conditioning and post-pregnancy fetal maintenance by clinical intervention stage. Post-marketing research showed that only three products had undergone safety evaluations and one involved pharmacoeconomic research， indicating a general lack of standardized evidence-based data. Dosage forms were mainly pills and granules. Package insert analysis revealed that 15 products listed "contraindications"， while 28 included "precautions". Based on prescription inclusion and exclusion criteria， 25 products were selected for further analysis. Their therapeutic effects were mainly concentrated on "tonifying the kidney and spleen， replenishing Qi， and nourishing blood"， with core medicines including Paeoniae Radix Alba， Angelicae Sinensis Radix， and Atractylodis Macrocephalae Rhizoma. Most medicines were warm or neutral in nature， predominantly sweet and pungent in flavor， and mainly entered the spleen， liver， and kidney meridians. ConclusionTraditional Chinese patent medicines for treating abortion demonstrate clear clinical value. However， shortcomings remain， including insufficient post-marketing research， prescription homogeneity， and incomplete package inserts. Future efforts should establish a clinically value-oriented modern development pathway， strengthen safety surveillance and evidence evaluation， improve package inserts， and promote precision use to further enhance clinical value.

ObjectiveThis study aims to systematically review the marketed traditional Chinese patent medicines for treating chronic gastritis （CG） in China. By analyzing their variety characteristics and prescription patterns， it seeks to provide references for clinical syndrome differentiation-based drug selection， treatment method optimization， and the design of high-quality clinical research. MethodsInformation on marketed traditional Chinese patent medicines for treating CG was collected. Microsoft Excel software was used to collate and statistically analyze representative drugs for each pathological stage， market status， syndrome types， and other contents. The Ancient and Modern Medical Case Cloud Platform （V2.3.9） was employed to analyze the formula composition patterns of standardized prescriptions. ResultsA total of 141 marketed traditional Chinese patent medicines for treating CG in China were included. Based on the disease's pathological progression， they can be classified into drugs for non-atrophic gastritis， atrophic gastritis， and precancerous lesions. Post-marketing research reveals that relevant evaluation is only conducted on 17 drugs， of which 2 involve pharmacoeconomic studies and 14 possess standardized evidence-based evidence. The primary dosage forms were capsules， granules， and tablets. From the 100 prescriptions screened according to inclusion/exclusion criteria， the varieties indicated for the stomach collateral stasis syndrome in atrophic gastritis accounted for the highest proportion. The main efficacy distributions were clearing heat， detoxifying， and relieving pain by promoting Qi circulation. Core drugs included Glycyrrhizae Radix et Rhizome， Paeoniae Radix Alba， and Aucklandiae Radix. Medicinal properties were predominantly warm and neutral. Flavors were mainly bitter， pungent， and sweet. The drugs primarily entered the spleen and stomach meridians. Analysis of the package inserts reveals that 67 products list "contraindications"， 110 include "precautions"， and 23 explicitly state "adverse reactions". ConclusionTraditional Chinese patent medicines for treating CG hold unique value in clinical practice. However， currently there are challenges such as insufficient clarity in syndrome type descriptions within package inserts and a relative lack of high-level evidence-based medical evidence， as well as pharmacoeconomic evaluations. Future efforts should focus on addressing these shortcomings by advancing research on syndrome characteristics and medication patterns based on syndrome differentiation， systematically conducting pharmacoeconomic evaluations， strengthening the accumulation of high-level evidence-based evidence， and， on this basis， improving patient medication adherence. This will comprehensively enhance the clinical application value and scientific connotation of this category of drugs.

ObjectiveThis study focused on the marketed Chinese patent medicines for the treatment of Functional Diarrhea （FDr） in China and their prescription characteristics， in order to provide support for the clinical application and research and development of anti-FDr Chinese patent medicines. MethodsCollect the information of Chinese patent medicines that have been marketed to treat FDr， use Microsoft Excel 2021 software to conduct preliminary data collation and statistical analysis， and use the ancient and modern medical record cloud platform （V2.3.9） to analyze the standardized Chinese patent medicine prescriptions from the aspects of drug nature and taste， medication characteristics and prescription rules. Results147 kinds of FDr Chinese patent medicines were included in this study. There are a total of 40 varieties of FDr Chinese patent medicines suitable for children； The distribution of dosage forms is mainly pills， tablets， and capsules. 110 prescriptions were screened， among which the proportion of Chinese patent medicines for the treatment of spleen deficiency syndrome was the highest； The top three drug use frequency were licorice， Atractylodes macrocephala， and Poria cocos； The medicinal properties are mainly warm and flat， and the medicinal taste is mostly pungent， sweet and bitter， and most of them belong to the two meridians of the spleen and stomach； The association rules analysis obtains 20 strong association pairing sets； Three drug combinations were obtained by cluster analysis. ConclusionFDr Chinese patent medicine shows unique value in clinical application， especially in the field of children. However， there are still problems such as strong professionalism in the indication expression of drug instructions， limited coverage of the medical insurance catalog， and lack of high-level evidence-based medicine and pharmacoeconomic evidence. To this end， in the future， efforts should be made to build a multi-level evidence-based evidence system， improve medication compliance， and deepen research on syndrome-based medication laws， so as to enhance the clinical application value and scientific connotation of FDr Chinese patent medicines.

ObjectiveTo study the marketed products and prescription characteristics of Chinese patent medicines for rheumatoid arthritis （RA） in China， thus providing support for clinical application and innovative research and development of Chinese patent medicines for RA. MethodsInformation on marketed Chinese patent medicines for RA treatment was collected. Preliminary data organization and statistical analysis were performed in Microsoft Excel 2021. Subsequently， the standardized prescriptions were analyzed via the Ancient and Modern Medical Case Cloud Platform （V2.3.9） across dimensions including medicinal properties， flavors， channel tropisms， usage characteristics， and formulation patterns. ResultsThis study ultimately included 311 marketed Chinese patent medicines for RA in China. Their initial market launch dates were mostly concentrated from the 1990s to the early 21st century. The National Basic Medical Insurance， Work-Related Injury Insurance， and Maternity Insurance Drug Directory included 89 Chinese patent medicines for RA. The primary dosage forms were tablets， capsules， medicated wines， and pills. After screening， 237 prescriptions were obtained， and the research on their origins was lagging. Among them， the Chinese patent medicines for treating wind-cold-dampness obstruction syndrome accounted for the highest proportion. The top three most frequently used medicinals were Angelicae Sinensis Radix， Notopterygii Rhizoma et Radix， and Saposhnikoviae Radix. Medicinal properties were primarily warm and plain， and flavors were mostly pungent， sweet， and bitter. The medicinals predominantly exhibited the liver and spleen channel tropism. Association rule analysis revealed that the herb pairs with the highest confidence were Chuanxiong-Angelicae Sinensis Radix and Myrrha-Olibanum. Cluster analysis yielded three medicinal combinations. ConclusionAlthough Chinese patent medicines for RA have application advantages， issues such as narrow syndrome coverage and insufficient innovation in dosage forms exist. Future development should focus on constructing an evidence-based system， strengthening the textual research on prescription origins and the exploration of classical famous formulas， and promoting dosage form innovation and precise medication to enhance their clinical value.

Background Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

To systematically analyzed the reporting status of core elements in publicly available clinical practice guideline(hereafter referred to as "guideline") protocols published domestically and internationally over the past decade, identified existing problems, and provided evidence to inform the standardized writing and publication of future guideline protocols.

ObjectiveA mouse model of vaccinia virus Tiantan strain (VTT)-induced encephalopathy was developed using AG6 mice. MethodsVTT was amplified by infecting Vero cells at a multiplicity of infection (MOI) of 0.01, followed by concentration and titration. After 72 h of incubation, virus-containing cells were collected and subjected to concentration. The concentrated viral suspension was serially diluted (10-fold dilutions) and added to 6-well plates containing confluent Vero cell monolayers for plaque assay. The number of plaques formed in each well was counted, and the virus titer was calculated based on the dilution factor. Fourteen 5-6-week-old AG6 mice (half male and half female, housed separately by sex) were randomly divided into a control group (n=3, PBS), a low-dose group (n=6, 1×10⁵ PFU), and a high-dose group (n=5, 5×10⁵ PFU). The mice were anesthetized by isoflurane inhalation and then infected via intranasal instillation. The mental state of the mice in each group was observed daily, and the body weight and mortality were recorded. On day 13 post-infection, 2% Evans Blue (4 mL/kg body weight) was administered via tail vein injection to assess blood-brain barrier (BBB) disruption. Subsequently, brain tissue samples were collected for immunofluorescence analysis to evaluate the activation of astrocytes and microglia. ResultsThe titer of purified VTT was 1×10⁷ PFU/mL. Compared with the control group, mice in the low-dose group showed no significant change in body weight, and no lethality was observed. In contrast, mice in the high-dose group exhibited significant weight loss starting on day 5 post-infection (P<0.05), accompanied by lethality. On day 13 post-infection, no Evans Blue extravasation was detected in the brain tissues of the low-dose group, while the olfactory bulb region of the high-dose group displayed distinct blue staining, indicating disruption of the BBB. Immunofluorescence analysis revealed no significant proliferation of astrocytes and microglia in the olfactory bulb region of the low-dose group on day 13 post-infection. In contrast, marked activation of glial cells was observable in the high-dose group. ConclusionAn animal model of VTT-induced encephalopathy in AG6 mice is successfully established, characterized by BBB disruption and reactive gliosis specifically localized to the olfactory bulb region, manifested as astrocytic and microglial proliferation.