This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

OBJECTIVE: To evaluate the effectiveness of early internal fixation combined with free anterolateral thigh perforator flap (ALTPF) transplantation in the treatment of open ankle fracture-dislocation. METHODS: A retrospective analysis was performed on the clinical data of 13 patients with open ankle fracture-dislocation who were admitted and met the inclusion criteria between January 2021 and May 2024. Among them, there were 9 males and 4 females, with the ages ranging from 23 to 61 years (mean, 45.3 years). Fracture types included 5 cases of simple medial or lateral malleolar fracture-dislocation, 7 cases of bimalleolar (medial and lateral) fracture-dislocation, and 1 case of trimalleolar fracture-dislocation. Additionally, 3 cases were complicated with bone defects (1 medial malleolus defect and 2 lateral malleolus defects). All injuries were classified as type ⅢB according to the Gustilo-Anderson classification for open fractures. The size of wound defects ranged from 7 cm×5 cm to 18 cm×12 cm. The time from injury to surgery was 2-20 hours (mean, 4 hours). All patients underwent emergency thorough debridement upon admission. The fracture-dislocation was temporarily stabilized with an external fixator, and the wound was covered with antibiotic-impregnated bone cement sheets or vacuum sealing drainage. Definitive internal fixation of the fracture and free ALTPF transplantation were performed 5-7 days after the initial emergency procedure. Postoperatively, wound healing, flap survival, and fracture union were monitored. At last follow-up, clinical outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. RESULTS: All 13 patients were followed up 6-24 months (mean, 8.2 months). All flaps survived completely, and all fractures achieved union, with an union time of 3-11 months (mean, 5.5 months). One patient developed a superficial infection at the wound margin, which healed after regular dressing changes and drainage. No internal fixation-related complication (e.g., deep infection, implant loosening, or secondary ankle instability) were observed. At last follow-up, the total AOFAS ankle-hindfoot score was 78.6±13.5, with 3 excellent, 7 good, 2 fair, and 1 poor cases, yielding an excellent and good rate of 76.9%. CONCLUSION Early internal fixation combined with ALTPF transplantation for open ankle fracture-dislocation can shorten the treatment course and maximize the recovery of ankle joint function.
Humans ; Fracture Fixation, Internal/methods* ; Male ; Middle Aged ; Female ; Adult ; Retrospective Studies ; Perforator Flap/transplantation* ; Ankle Fractures/surgery* ; Thigh/surgery* ; Fractures, Open/surgery* ; Treatment Outcome ; Young Adult ; Plastic Surgery Procedures/methods* ; Fracture Dislocation/surgery*

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVE: To explore the effect of acupuncture therapy on dysphagia in patients with Parkinson's disease. METHODS: This randomized controlled study lasted 42 days and included 112 patients with Parkinson's disease and dysphagia. Participants were randomly assigned to the experimental and control groups (56 cases each group) using the completely randomized design, all under routine treatment. The experimental group was given acupuncture therapy. The primary outcome was Penetration-Aspiration Scale (PAS). The secondary outcomes were (1) Standardized Swallowing Assessment (SSA), and (2) nutritional status including body mass index (BMI), serum albumin, prealbumin, and hemoglobin. Adverse events were recorded as safety indicators. RESULTS: One participant quitted the study midway. There were no significant differences in baseline assessment (P>0.05). After treatment, both groups showed significant improvement in PAS, SSA and nutritional status except for BMI of the control group. There were significant differences between the two groups in the PAS for both paste and liquid, SSA (25.18±8.25 vs. 20.84±6.92), BMI (19.97±3.34 kg/m²vs. 21.26 ±2.38 kg/m²), serum albumin (35.16 ±5.29 g/L vs. 37.24 ±3.98 g/L), prealbumin (248.33 ±27.72 mg/L vs. 261.39 ±22.10 mg/L), hemoglobin (119.09±12.53 g/L vs. 126.67±13.97 g/L) (P<0.05). There were no severe adverse events during the study. CONCLUSION: The combination of routine treatment and acupuncture therapy can better improve dysphagia and nutritional status in patients with Parkinson's disease, than routine treatment solely. (registration No. CLINICALTRIAL gov NCT06199323).
Humans ; Parkinson Disease/therapy* ; Deglutition Disorders/physiopathology* ; Acupuncture Therapy/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Treatment Outcome ; Nutritional Status ; Body Mass Index

Objective:To compare the clinical efficacy between a single palmar lateral transverse approach and the modified Henry approach in the locking plate fixation for distal radius fractures.Methods:A retrospective study was conducted to analyze the data of 82 patients with distal radius fracture who had undergone locking plate fixation through either a single palmar lateral approach or the modified Henry approach between January 2016 and December 2022 at Department of Traumatic Orthopaedics, Taihe Hospital, Affiliated to Hubei University of Medicine. There were 25 males and 57 females, with an age of (53.8±12.7) years. Based on the difference in surgical approach, the patients were divided into a single transverse approach group ( n=42) and a modified Henry approach group ( n=40). The 2 groups were compared in terms of injury cause, injury location, time from injury to surgery, AO fracture classification, tourniquet time during surgery, incision length, fracture reduction, Patient and Observer Scar Assessment Scale (PSAS & OSAS) and Disability of the Arm, Shoulder, and Hand (DASH) score at the last follow-up, and complications after surgery. Results:There were no statistically significant differences in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (8.2±3.5) months. Follow-ups revealed one case of injury to the palmar cutaneous branch of the median nerve but no other complications like infection, non-union, internal fixation failure, or tendon injury in the single transverse approach group. The single transverse approach group was significantly superior over the modified Henry approach group in incision length [(2.4±0.9) cm versus (5.3±1.6) cm], OSAS (8.1±4.2 versus 10.3±5.7), and PSAS (10.1±5.8 versus 14.7±6.4) ( P<0.05). There were no significant differences between the 2 groups in tourniquet time, fracture reduction quality, and DASH score at the last follow-up ( P>0.05). Conclusion:In locking plate fixation for distal radius fractures, in comparison with the modified Henry approach, a single palmar lateral approach is more minimally invasive so that more aesthetically pleasing outcomes can be achieved to facilitate patients' rapid return to work and society.

ObjectiveTo study the effect of Tanreqing injection （TRQ） on the pulmonary flora in the rat model of chronic obstructive pulmonary disease （COPD）. MethodWistar rats were randomized into control， model， and TRQ groups. The rats in other groups except the control group were treated by smoking combined with intratracheal instillation of lipopolysaccharide for the modeling of COPD. The TRQ group was intraperitoneally injected with TRQ （2 g·kg^-1）. At the end of the experiment， after blood collection from the abdominal aorta of the rats， the lung tissue was collected for hematoxylin-eosin and picric sirius red staining to reveal the pathological changes. The lung lavage fluid was collected， and the diversity and relative abundance of lung flora in different groups were analyzed by 16S rDNA amplicon sequencing. ResultThe lungs of the control group were normal， and those of the model group showed neutrophil infiltration， telangiectasia， lung hemorrhage and emphysema in individual cases， and thickening of collagen fibers in the trachea. Compared with the model group， the TRQ group showed significantly improved lungs and recovered collagen fibers. The MLI analysis showed that compared with the control group， the model group showcased increased alveolar space （P<0.01）， which was reduced in the TRQ group （P<0.05）. Compared with the control group， the model group showed increased wall thickness （P<0.01）， and the increase was attenuated in the TRQ group （P<0.01）. TRQ increased the Simpson index and altered the α diversity of pulmonary flora. The results of principal co-ordinate analysis showed that TRQ changed the β diversity and reduced the β diversity index of pulmonary flora. At the genus level， the model group showed increased relative abundance of g_Bacillus and g_Brevundimonas and decreased relative abundance of g_Pseudomonas， compared with the control group. After treatment with TRQ， the relative abundance of g_Stenotrophomonas increased， and that of g_Bacillus decreased. The LEfSe of differential taxa between groups showed that the modeling increased the relative abundance of g_Lachnospiraceae_NK4A136_group， and TRQ treatment increased the relative abundance of g_Rhodococcus and g_Stenotrophomonas. ConclusionTRQ can regulate the diversity of pulmonary flora and restore the balance of bacterial genera in the rat model of COPD， which may be one of the mechanisms of the prevention and treatment of COPD with TRQ.

Alzheimer's disease(AD)is the most common cognitive disorder in the elderly and manifests primarily as progressive cognitive function decline, neuropsychiatric symptoms and multiple functional impairments.Obstructive sleep apnea(OSA)is a common type of respiratory disorder.Studies have found that AD and OSA are connected in many ways, including the risk of developing these diseases, biomarkers and neuroimaging features.These connections may result from a variety of mechanisms, such as neuropathological protein deposition, exacerbated immune-mediated inflammation, oxidative stress abnormalities, impaired mitochondrial function, and disturbed neurotransmitter systems, among others.This article reviewed the relationship between AD and OSA, the mechanisms linking them and their treatment.

AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Objective: To explore the mechanism by which icariin alleviates viral myocarditis. Methods: CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability, inflammation, and apoptosis. Moreover, the effects of icariin on ferroptosis and TLR4 signaling were assessed. After AC16 cells were transfected with TLR4 overexpression plasmids, the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated. Results: Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α, IL-1β, IL-6, and IL-18. Flow cytometry revealed that icariin decreased apoptosis rate, and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes. Additionally, it suppressed ferroptosis including lipid peroxidation and ferrous ion, as well as the TLR4 signaling. However, TLR4 overexpression abrogated the modulatory effects of icariin. Conclusions: Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis. Further animal study is needed to verify its efficacy.