Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

To summarize the clinical experience of treating idiopathic olfactory disorder from the perspective of heart and lungs. It is believed that the sense of olfaction is based on the nose， rooted in the heart， functioning through the lungs， and conveyed by pectoral qi. The key pathogenesis of idiopathic olfactory disorder lies in the accumulation of pathogenic factors in the heart and lungs， blood vessel obstruction， the failure of the lungs to disperse and descend， and the loss of control of pectoral qi. In treatment， internal and external therapies could be combined. The internal therapy can correct the imbalance of the zang-fu organs， using the self-prescribed Bilong Formula （鼻聋方） to dispel wind and diffuse the lung， invigorate blood and relieving stuffy orifices； the external therapy can clear nasal obstruction， supplemented by intradermal needle embedding at three acupoints， bilateral Yingxiang （LI 20）， bilateral Shangyingxiang （EX-HN 8） and Yintang （GV 29）， and integrated olfactory training for comprehensive treatment.

Neuraminidase(NA),a glycoprotein on the surface of the influenza virus,plays a crucial role in viral escape and serves as a stable target for drug candidates.Monoclonal antibodies targeting the NA active site can bind to multiple influenza virus subtypes and inhibit the spread of influenza virus through various mechanisms,such as neutralizing,mediating antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotox-icity.In vivo experiments have shown that human monoclonal antibodies targeting the influenza virus NA can ef-fectively exert preventive and therapeutic effects,rescuing mice infected with lethal doses and reducing viral ti-ters in lungs of mice.This article provides a review of the currently reported human monoclonal antibodies targe-ting NA of Influenza A and Influenza B viruses,providing new ideas and prospects for the subsequent development of anti-influenza drugs.

Retinitis pigmentosa (RP) is a kind of ophthalmic hereditary disease characterized by degenerative dystrophy of photoreceptors in the retina.It is one of the main causes of hereditary visual impairment and blindness. USH2A gene is the primary pathogenic gene of both syndromic RP (e.g., Usher syndrome type Ⅱ, USH2) and non-syndromic RP, so elucidating its function and pathogenesis is of important theoretical significance and clinical application value.However, due to the wide range of USH2A gene variations, as well as USH2A protein has huge molecular weight and complex protein structure, the molecular pathogenesis of RP caused by USH2A variations remains unknown, which has hindered the progress of gene therapy and also poses many challenges to researchers and clinicians.Recently, with the development of gene editing technology and the establishment of animal models, the function of USH2A gene has been further studied.For example, USH2A is involved in cell adhesion at retinal basal membrane.USH2A interacts with other USH proteins to maintain photoreceptor structure and plasticity.USH2A can participate in vesicle transport from the inner segment to the outer segment of photoreceptors.USH2A maintains the normal function of photoreceptor cells by regulating autophagy.This article reviews the pathogenesis of RP induced by variations of USH2A gene.

Objective To investigate the abnormal changes characteristics of the degree centrality(DC)of the brain functional network in patients with benign paroxysmal positional vertigo(BPPV)in the classical frequency band(0.010-0.080 Hz),the slow-4 frequency band(0.027-0.073 Hz),and the slow-5 frequency band(0.010-0.027 Hz).Methods Twenty patients with BPPV(BPPV group)and 14 healthy controls(HC)(HC group)were selected.Resting-state functional magnetic resonance imaging(rs-fMRI)scans were performed,and the clinical data were analyzed.The DC method was used to analyze the changes of centrality of resting state network in patients with BPPV.Results Compared with the HC group,the BPPV group showed an increase in DC in the left caudate nucleus in the classical frequency band(P＜0.05),and a decrease in DC in the right auxiliary motor region in the classical frequency band(P＜0.05);within the slow-4 frequency band,no significant differences were observed in brain regions(P＞0.05);within the slow-5 frequency band,the BPPV group showed an increase in DC in the left thalamus(P＜0.05),while the left anterior cingulate and paracingulate gyrus showed a decrease in DC(P＜0.05).Conclusion Patients with BPPV have spontaneous activity disorders in multiple brain regions at resting states,and these changes show frequency band specificity.

Objective To investigate the effects of galectin-3(Gal3)on autophagy in high glucose-induced human telomerase reverse transcriptase-immortalized retinal pigment epithelial(hTERT-RPE)cells.Methods The hTERT-RPE cells cultured in vitro were randomly divided into a normal group(group C),a high glucose group(group HG),a high glu-cose+si-NC group(group HG+si-NC)and a high glucose+si-Gal3 group(group HG+si-Gal3).Reverse transcrip-tion polymerase chain reaction(RT-PCR)was used to detect the relative mRNA expression levels of Gal3,intercellular ad-hesion molecule(ICAM)-1,interleukin(IL)-6 and tumor necrosis factor(TNF)-α in hTERT-RPE cells of each group.The expression levels of IL-1 and IL-6 in the supernatant of hTERT-RPE cells were measured by enzyme-linked immunosorbent assay(ELISA).The expression level of reactive oxygen species(ROS),the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in hTERT-RPE cells were analyzed by dichlorofluorescin diacetate(DCFH-DA)staining,the colorimetric method and the microplate method,respectively.The protein expression levels of Gal3,the ratio of microtubule associated protein 1 light chain 3(LC3)type Ⅱ to type Ⅰ(LC3 Ⅱ/LC3 Ⅰ),Beclin 1,and autophagy-associat-ed 5(ATG5)and 7(ATG7)in hTERT-RPE cells from each group were detected by Western blot analysis.After the hTERT-RPE cells in each group were transfected with double fluorescent mRFP-GFP-LC3 plasmids alone and with RFP-LAMP1 and GFP-LC3 plasmids jointly,the changes of autophagy flow in hTERT-RPE cells were detected by laser confocal microscopy.Results Compared with the group C,the group HG showed an increase in the expression of Gal3,IL-1,IL-6,TNF-α,ICAM-1,P62,ROS and MDA content(all P＜0.05).However,the expression of LC3 Ⅱ/LC3 Ⅰ,Beclin1,ATG7,ATG5,the SOD activity,and the number of red(autolysosomes)and yellow fluorescence spots(autophagosomes)of the double fluo-rescent mRFP-GFP-LC3 plasmid were all lower in the group HG than those in the group C(all P＜0.05).There was no sig-nificant difference in the number of yellow fluorescent spots(autolysosomes)co-located by RFP-LAMP1 and GFP-LC3 plas-mids between groups C and HG(P＞0.05).There were no significant differences in the expression levels of the above-mentioned indexes in hTERT-RPE cells between groups HG and HG+si-NC(all P＞0.05).The expression levels of Gal3,IL-1,IL-6,TNF-α,ICAM-1,P62,ROS and MDA content in hTERT-RPE cells of the group HG+si-Gal3 were lower than those of the group HG+si-NC(all P＜0.05).Compared with those in the group HG+si-NC,the expression levels of LC3 Ⅱ/LC3 Ⅰ,Beclin1,ATG7,ATG5,SOD activity,and the number of red and yellow fluorescent spots of the double fluo-rescent mRFP-GFP-LC3 plasmid were increased in the group HG+si-Gal3(all P＜0.05).There was no significant differ-ence in the number of yellow fluorescent spots co-located by RFP-LAMP1 and GFP-LC3 plasmids between groups HG+si-GaL3 and HG+si-NC(P＞0.05).Conclusion Gal3 is significantly elevated in hTERT-RPE cells induced by high glu-cose,resulting in impaired autophagy flow.It produces a direct regulatory effect on the formation of autophagosomes,and plays a highly active role in oxidative damage and expression of inflammatory factors in hTERT-RPE cells induced by high glucose.

Objective To construct a risk prediction model for intraoperative acquired pressure injury(IAPI)during neurosurgery in pediatric patients,and verify the predictive effect of the model,to provide a reference for preventing IAPI during neurosurgery in pediatric patients.Methods The clinical data of 776 pediatric patients undergoing neurosurgery in a tertiary-level hospital in Chongqing from January to June 2023 were retrospectively collected.The risk factors for IAPI were explored through univariate analysis and binary Logistic regression analysis.The fitting degree and predictive effect of the model were verified by Hosmer-Lemeshow test and receiver operator characteristic(ROC)curve,respectively.The model was validated internally by Bootstrap.Results The incidence of IAPI during neurosurgery in pediatric patients was 7.99％.Logistic regression analysis showed that bleeding volume,anesthesia time,age,intraoperative use of instruments such as drills and milling cutters that increase external force,and surgical position were the factors influencing IAPI in neurosurgical children(all P＜0.05).The results of the Hosmer-Lemeshow test showed that x2=3.636,P=0.888.The results of internal verification showed that the sensitivity of the model was 0.59;the specificity was 0.81;the area under the ROC curve was 0.79.Conclusion This study analyzes the risk factors for IAPI during neurosurgery in pediatric patients and constructs a line chart prediction model with good predictive performance,which can provide a reference for individualized prediction of the risk of IAPI during neurosurgery in pediatric patients.It can provide a scientific basis for clinical nursing staff to identify high-risk children with IAPI early and take personalized preventive measures in time.

OBJECTIVE To evaluate the quality of diagnosis and treatment guidelines and expert consensuses on childhood immune thrombocytopenic purpura(ITP)published domestically and internationally,in order to provide reference for clinical practice and future guideline/expert consensus development and improvement.METHODS A systematic search was conducted across multiple databases,including PubMed,Cochrane Library,Embase,CNKI,Wanfang data,VIP,CBM;additionally,supplementary searches were carried out on websites such as Medlive,the Chinese Medical Association's official website,and National Institute for Health and Clinical Excellence in the UK.The retrieval time ranged from the inception to September 2,2024.Researchers who had undergone systematic training independently evaluated the methodology and report quality included in the guideline/consensus using the Appraisal of Guidelines Research and Evaluation Ⅱ(AGREE Ⅱ)and the Reporting Items for Practice Guidelines in Healthcare(RIGHT).RESULTS A total of 11 guidelines/consensuses were included.The average scores for the six domains of AGREE Ⅱ tool respectively were"range and purpose"[(66.67±17.98)%],"participants"[58.33%(13.89%,73.61%)],"rigor"[(41.81±23.85)%],"clarity"[(69.57±19.35)%],"applicability"[(35.98±17.83)%],and"independence"[27.08%(0,75.00%)];out of 11 articles,9 had a recommendation level of B,2 had a recommendation level of C,and there were no A-level articles.The average reporting rates of the 7 areas in the RIGHT tool were"basic information"[(72.35±12.95)%],"background"[(54.55±15.40)%],"evidence"[(36.36±24.81)%],"recommended opinions"[(53.25±19.20)%],"review and quality assurance"[0(0,25.00%)],"funding and conflict of interest statement and management"[12.50%(0,25.00%)],and other aspects[8.33%(0,50.00%)].In addition,there was no statistically significant difference in the AGREE Ⅱ and RIGHT scores between the guidelines and consensuses(P＞0.05).CONCLUSIONS The overall quality of the guidelines and consensuses included in this study is not high,with a recommended level of B or C.It is recommended that clinical decision-making prioritize referring to the relatively high-quality guideline/consensus among them.The quality of evidence in the existing traditional Chinese medicine guidelines for children with ITP needs to be improved,and there is no integrated guideline/consensus for traditional Chinese and Western medicine.It is recommended to revise or write relevant guideline/consensus according to the requirements of AGREE Ⅱ and RIGHT in various fields to guide clinical practice.

Objective:To analyze the dynamic plantar pressure distribution of persons with chronic plantar fasciitis (PF).Methods:Twenty persons with unilateral, chronic PF were recruited as the PF group, while twenty-three healthy counterparts were recruited as the control group. A foot-pressure measurement system was used to collect data describing the plantar pressure for each subject with or without PF while walking. The pressure data included the load of peak plantar pressure (PP), the mean plantar pressure (MP), the total foot ground contact area (TCA), and the load percentage and the foot ground contact area beneath the medial heel (MH), the lateral heel (LH), the medial longitudinal arch (MLA), the lateral longitudinal arch (LLA), the first metatarsal head (M1), the second to third metatarsal heads (M2-3), the fourth to fifth metatarsal heads (M4-5), the hallux (T1), and toes two to five (T2-5).Results:In the PF group, significant differences were observed during walking between the affected and unaffected feet in terms of PP [(2.41±0.44)kg/cm 2 versus (3.02±0.63)kg/cm 2]. Both were significantly greater than among the control group. Asymmetry in the load distribution was identified beneath the MH, M2-3, M1, MLA, M4-5 and T2-5 among the chronic PF group. There were also significant differences between the affected foot of the chronic PF group and the non-dominant foot of the control group with regard to the load percentage beneath the LH, M4-5, T2-5, M2-3 and T1. The load percentage under the LH was significantly higher under the unaffected foot of the PF group than under the dominant foot of the control group. In terms of ground contact area, the T2-5 area of the affected foot of the PF group was significantly smaller than that of the unaffected foot, as well as compared to the non-dominant foot of the control group. The TCA of both feet among the PF group was significantly smaller than under the corresponding feet of the control group. Conclusions:Patients with chronic plantar fasciitis apply plantar pressure asymmetrically during walking. They tend to shift their weight laterally onto the asymptomatic foot. During walking, those with PF apply higher plantar pressure over a smaller ground contact area.

Objective:To observe any therapeutic effect of repeated high-frequency transcranial magnetic stimulation (rTMS) on patients with medication overuse headache (MOH).Methods:Fifty-seven persons with MOH were divided at random into a control group of 29 cases and an rTMS group of 28 cases. Both groups of patients stopped taking analgesics and were treated with topiramate and trazodone. The rTMS group received an additional 20 minutes of rTMS treatment daily, 5 days a week for 8 consecutive weeks. The control group received sham stimulation. Before and after the treatment, both groups′ headache symptoms, disability, depression, anxiety, cognition and sleep quality were evaluated using a visual analog scale (VAS) for pain, a migraine disability assessment scale (MIDAS), the Montreal cognitive assessment (MoCA), the Hamilton depression scale (HAMD), the Hamilton anxiety scale (HAMA) and the Pittsburgh sleep quality index (PSQI). Auditory event-related potential P300 was also measured for both groups.Results:After the treatment, the average VAS, MIDAS, HAMD, HAMA and PSQI scores of both groups had decreased significantly. The HAMD, HAMA and PSQI average scores of the rTMS group were then significantly better than the control group′s averages. The average MoCA score of the rTMS group had also improved significantly. The average latency of the auditory event-related potential P300 in the rTMS group was then (368.25±9.25)ms and its amplitude was (6.62±1.40)μV, showing significant improvement compared to before the treatment and compared with the control group.Conclusions:On the basis of oral administration of topiramate and trazodone, additional high-frequency rTMS treatment can significantly alleviate anxiety and depression in MOH patients, and improve their sleep quality and the latency and amplitude of event-related potential P300.