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.

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 clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Objective: To investigate the longitudinal association between attention deficit hyperactivity disorder (ADHD) symptoms and Internet gaming addiction among junior and senior high school students, as well as gender differences in the association, so as to provide evidence for understanding the complex interactions underlying adolescent mental health problems. Methods: Using stratified random cluster sampling, two surveys were conducted among 2 100 junior and senior high school students from six schools in Bijie City, Qianxi City, and Jinsha County, Guizhou Province, from January to March 2023 (T1) and from July to September 2023 (T2). ADHD symptoms were assessed using the Barkley Current Symptoms Scale (BCSS), and Internet gaming addiction was assessed using the Internet Gaming Disorder Scale-Short Form (IGDS9-SF). Pearson correlation analysis, cross lagged model, and multi group models were used to examine the longitudinal relationship between ADHD symptoms and Internet gaming addiction and to test gender differences. Results: The detection rate of Internet gaming addiction was 4.57% at T1. ADHD symptoms were positively correlated with Internet gaming addiction at T1 and T2 time points ( r =0.32-0.80, all P < 0.05 ). Cross lagged analysis showed that T1 ADHD symptoms positively predicted T2 ADHD symptoms ( β =0.85) and T2 Internet gaming addiction ( β =0.65) (both P <0.01). Gender stratified analyses showed that T1 ADHD symptoms positively predicted T2 ADHD symptoms among both boys and girls ( β =0.91, 0.84) and T2 Internet gaming addiction ( β =0.31, 0.29) (all P <0.01). Multi group difference tests showed a statistically significant gender difference in the T1 ADHD→T2 ADHD pathway (Wald χ 2= 7.27 , P < 0.01 ), whereas no statistically significant gender difference was found in the T1 ADHD→T2 Internet gaming addiction pathway (Wald χ 2=1.07, P > 0.05 ). Conclusions ADHD symptoms are antecedent risk factors for Internet gaming addiction among junior and senior high school students. The longitudinal predictive effect of ADHD symptoms on subsequent Internet gaming addiction is present in both boys and girls, with no gender difference in the predictive pathway.

Objective To summarize the current status and trends of clinical research on gallbladder cancer (GBC) from 2016 to 2026. Methods Literature of GBC clinical research published from 2016 to 2026 was collected from the Web of Science Core Collection. VOSviewer 1.6.21 software was applied to perform cluster and chronological analyses on countries, academic institutions, authors, and keywords of the included publications, alongside cluster analysis on co-citation references. The visualization maps were generated to analyze collaborative networks among countries, academic institutions, and researchers, and to predict the future research hot spots and directions. Results A total of 411 publications in English were included. From 2016 to 2026, the amount of literature on GBC clinical research has shown a fluctuating upward trend, with publications concentrated mainly in professional journals in the field of oncology. China ranks first globally in the publication output, but its average citation is lower than that of United Kingdom and Germany. Institutions of publications exhibit distinct regional clustering characteristics, with close collaboration within regions but a need for strengthened cross-regional collaboration. Keyword analysis reveals that research hot spots are shifting from traditional surgical treatment toward systemic therapy, immunotherapy, and precision medicine, which may represent future development directions. Conclusions Clinical research on GBC has flourished from 2016 to 2026, with global publication output showing a fluctuating upward trend. China leads in publication amount, but the quality of articles and citation counts still need improvement. To foster continued development and transformation in GBC, it is necessary to strengthen cross-regional international collaboration, promote the integration of precision medicine and systemic therapy, and emphasize patient-centered research strategies.

This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history* ; Humans ; Medicine, Chinese Traditional/history* ; History, Ancient ; Astragalus Plant/chemistry* ; China ; Astragalus propinquus

Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.

Objective To investigate the effect of splenectomy on the repair of full-thickness skin tissue defects,as well as the impact of different recovery times after splenectomy on the healing of skin tissue defects.Methods According to a random number table,39 8-week-old female C57 mice were randomly divided into three groups:sham surgery group(sham group,n=13),splenectomy group with 3 days of recovery(Spx3d group,n=13),and splenectomy group with 3 weeks of recovery(Spx3w group,n=13).Full-thickness skin defects were created on the backs of the mice in each group.The wound healing conditions at different times after skin defects were observed,and the wound healing rates after the injury were calculated.Peripheral blood cell analysis was performed on day 14 after the defect,and tissue samples from the wound area were taken for hematoxylin and eosin(HE)staining to observe the granulation tissue thickness at the defect site and the re-epithelialization rate.Masson's trichrome staining was used to observe the proportion of collagen fibers.Results After splenectomy and sham surgery,the mice recovered well without significant discomfort.From 1 to 14 days after the skin defect modeling,the wound areas of the mice in all three groups gradually decreased.Compared with sham group,the wound areas were smaller in Spx3d and Spx3w groups at 3,5 and 7 days after the injury,and the differences were statistically significant(P<0.05).The wound healing rates were also significantly higher(P<0.05).Moreover,at 3 days and 5 days after the injury,the wound healing rates of Spx3d group were significantly higher than those of Spx3w group(P<0.05 or P<0.01).The peripheral blood white blood cell(WBC)count in Spx3w group was significantly higher than that in sham group and Spx3d group(P<0.01).The platelet counts in both sham group and Spx3w group were significantly higher than that in Spx3d group(P<0.05).Additionally,the lymphocyte and neutrophil counts in Spx3w group were markedly higher than those in sham group(P<0.05).No statistically significant differences in red blood cell(RBC)counts were observed among the three groups(P>0.05).HE staining results showed that compared with sham group,the wound healing of the mice in Spx3d and Spx3w groups were better,and the thickness of the granulation tissue in Spx3d group were better than that in Spx3w group.At 7 days,the thickness of the granulation tissue in Spx3d and Spx3w groups was significantly higher than that in sham group(P<0.01,P<0.05)and the re-epithelialization rate in Spx3d group was significantly higher than that in sham group and Spx3w group(P<0.05).At 14 days,the re-epithelialization rates of Spx3d and Spx3w groups were significantly higher than those of sham group(P<0.05).The results of Masson's staining showed that the collagen fiber proportion in the wounds of Spx3d group at 7 and 14 days and that of Spx3w group at 14 days were significantly higher than that in sham group(P<0.05).Conclusion The healing of skin defects in mice is accelerated after splenectomy,and the recovery time after splenectomy has a certain effect on the healing of skin defects.

Objective To investigate the characteristics of thickness changes in peripapillary retinal nerve fiber layer(pRNFL)and identify related risk factors in patients with Moyamoya disease(MMD).Methods A retrospective study was conducted on 150 MMD patients(150 eyes)aged 6-65 years admitted to the Neurosurgery Department of the Fifth Medical Center,Chinese PLA General Hospital from May 2016 to December 2023(observation group),and 150 age-matched healthy volunteers(150 eyes)from the hospital's ophthalmology outpatient department(control group).Both groups were subdivided into pediatric(≤18 years),young adult(18-40 years),and middle-aged(40-65 years)subgroups.The pRNFL thickness in four quadrants was measured by optical coherence tomography(OCT):superior(pRNFL-Sup),inferior(pRNFL-Inf),nasal(pRNFL-Nas),temporal(pRNFL-Tmp),and average thickness(pRNFL-Avg).General clinical data and pRNFL thickness were compared between two groups.Univariate and multivariate logistic regression analyses were performed to identify risk factors for pRNFL thinning in MMD patients.The cohort was randomly divided into training(n=210)and validation(n=90)sets at a 7:3 ratio.A predictive model for pRNFL thinning in MMD patients was constructed based on logistic regression results.Model performance was evaluated using the area under the receiver operating characteristic curve(AUC),and clinical utility was assessed via decision curve analysis.Results Compared with control group,MMD patients exhibited significantly reduced pRNFL-Avg,pRNFL-Sup,pRNFL-Tmp,and pRNFL-Inf thickness(P<0.05 or P<0.001),while pRNFL-Nas showed no significant difference(P>0.05).In the pediatric subgroup,pRNFL-Avg and pRNFL-Inf were thinner(P<0.05).In the young adult subgroup,pRNFL-Avg and pRNFL-Sup were reduced(P<0.001 or P<0.05).In the middle-aged subgroup,pRNFL-Avg,pRNFL-Sup,pRNFL-Inf,and pRNFL-Tmp were all thinner(P<0.05 or P<0.001).Multivariate logistic regression identified visual field defects(OR=15.28,95%CI 2.95-79.10),disease duration(OR=1.11,95%CI 1.05-1.18),and the number of involved cerebral vessels(OR=1.49,95%CI 1.01-2.22)as independent risk factors for pRNFL thinning.The predictive model achieved AUC of 0.94(95%CI 0.91-0.97)and 0.95(95%CI 0.91-0.99)in the training and validation sets,respectively.Decision curve analysis confirmed the model's favorable clinical net benefit.Conclusion Thinning of pRNFL was observed in Moyamoya disease patients with visual field defects,disease duration,and cerebral vascular involvement identified as independent risk factors for pRNFL atrophy.