Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVE: To explore short-term effectiveness of floating island laminectomy surgery in treating thoracic spinal stenosis and myelopathy caused by ossification of the ligamentum flavum. METHODS: A total of 31 patients with thoracic spinal stenosis and myelopathy caused by ossification of the ligamentum flavum between January 2019 and April 2022 were managed with floating island laminectomy surgery. The patients comprised 17 males and 14 females, aged between 36 and 78 years, with an average of 55.9 years. The duration of symptoms of spinal cord compression ranged from 3 to 62 months (mean, 27.2 months). The lesions affected T _1-6 in 4 cases and T _7-12 in 27 cases. The preoperative neurological function score from the modified Japanese Orthopaedic Association (mJOA) was 4.7±0.6. Surgical duration, intraoperative blood loss, and complications were recorded. The thoracic MRI was conducted to reassess the degree of spinal cord compression and decompression after operation. The mJOA score was employed to evaluate the neurological function and calculate the recovery rate at 12 months after operation. RESULTS: The surgical duration ranged from 122 to 325 minutes, with an average of 204.5 minutes. The intraoperative blood loss ranged from 150 to 800 mL (mean, 404.8 mL). All incisions healed by first intention after operation. All patients were followed up 12-14 months, with an average of 12.5 months. The patients' symptoms, including lower limb weakness, gait disorders, and pain, significantly improved. The mJOA scores after operation significantly increased when compared with preoperative scores ( P<0.05), gradually improving with time, with significant differences observed among 1, 3, and 6 months ( P<0.05). The recovery rate at 12 months was 69.76%±11.38%, with 10 cases exhibiting excellent neurological function and 21 cases showing good. During the procedure, there were 3 cases of dural tear and 1 case of dural defect. Postoperatively, there were 2 cases of cerebrospinal fluid leakage. No aggravated nerve damage, recurrence of ligamentum flavum ossification, or postoperative thoracic deformity occurred. CONCLUSION The floating island laminectomy surgery is safe for treating thoracic spinal stenosis and myelopathy caused by ossification of the ligamentum flavum, effectively preventing the exacerbation of neurological symptoms. Early improvement and recovery of neurological function are achieved.
Humans ; Male ; Spinal Stenosis/diagnostic imaging* ; Female ; Laminectomy/methods* ; Ligamentum Flavum/pathology* ; Middle Aged ; Aged ; Thoracic Vertebrae/surgery* ; Adult ; Decompression, Surgical/methods* ; Treatment Outcome ; Ossification, Heterotopic/surgery* ; Spinal Cord Compression/etiology* ; Spinal Cord Diseases/etiology* ; Magnetic Resonance Imaging

OBJECTIVE: To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO). METHODS: Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications. RESULTS: The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05). CONCLUSION Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans ; Male ; Female ; Middle Aged ; Radius Fractures/physiopathology* ; Adult ; Bone Plates ; Fracture Fixation, Internal/methods* ; External Fixators ; Retrospective Studies ; Fracture Fixation/methods* ; Wrist Fractures

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*

BACKGROUND: A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain. OBJECTIVE: This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment. SEARCH STRATEGY: We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025. INCLUSION CRITERIA: (1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs). DATA EXTRACTION AND ANALYSIS: Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence. RESULTS: Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: -9.2; 95% confidence interval [CI]: [-16.0, -2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: -41.0; 95% CI: [-66.0, -16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and Lactobacillus casei strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality. CONCLUSION Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings. Please cite this article as: Chen CS, Wen L, Yang F, Deng YC, Ji JH, Chen RJ, Chen Z, Chen G, Gu JY. Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis. J Integr Med. 2025; 23(4): 357-369.
Humans ; Dietary Supplements ; Osteoarthritis/drug therapy* ; Randomized Controlled Trials as Topic

Mitophagy, a highly precise form of autophagy, plays a pivotal role in maintaining cellular homeostasis by selectively targeting and eliminating damaged mitochondria through a process known as mitophagy. Within this tightly regulated mechanism, dysfunctional mitochondria are specifically delivered to lysosomes for degradation. Disruptions in mitophagy have been implicated in a diverse range of pathological conditions, spanning diseases of the nervous system, cardiovascular system, cancer, aging, and metabolic syndrome. The elucidation of mitophagy’s impact on cardiovascular disorders, liver diseases, metabolic syndromes, immune dysfunctions, inflammatory conditions, and cancer has significantly advanced our understanding of the complex pathogenesis underlying these conditions. These studies have shed light on the intricate connections between dysfunctional mitophagy and disease progression. Among the disorders associated with mitochondrial dysfunction, insulin resistance (IR) stands out as a prominent condition linked to metabolic disorders. IR is characterized by a diminished response to normal levels of insulin, necessitating higher insulin levels to trigger a typical physiological reaction. Hyperinsulinemia and metabolic disturbances often coexist with IR, primarily due to defects in insulin signal transduction. Oxidative stress, stemming from mitochondrial dysfunction, exerts dual effects in the context of IR. Initially, it disrupts insulin signaling pathways and subtly contributes to the development of IR. Additionally, by inducing mitochondrial damage and autophagy, oxidative stress indirectly impedes insulin signaling pathways. Consequently, mitophagy acts as a protective mechanism, encapsulating damaged or dysfunctional mitochondria through the autophagy-lysosome pathway. This efficient process eliminates excessive oxidative stress reactive. The intricate interplay between mitochondrial function, oxidative stress, mitophagy, and IR represents a captivating field of investigation in the realm of metabolic disorders. By unraveling the underlying complexities and comprehending the intricate relationships between these intertwined processes, researchers strive toward uncovering novel therapeutic strategies. With a particular focus on mitochondrial quality control and the maintenance of redox homeostasis, these interventions hold tremendous potential in mitigating IR and enhancing overall metabolic health. Emerging evidence from a myriad of studies has shed light on the active involvement of mitophagy in the pathogenesis of metabolic disorders. Notably, interventions such as exercise, drug therapies, and natural products have been documented to induce mitophagy, thereby exerting beneficial effects on metabolic health through the activation of diverse signaling pathways. Several pivotal signaling molecules, including AMPK, PINK1/Parkin, BNIP3/Nix, and FUNDC1, have been identified as key regulators of mitophagy and have been implicated in the favorable outcomes observed in metabolic disorders. Of particular interest is the unique role of PINK1/Parkin in mitophagy compared to other proteins involved in this process. PINK1/Parkin exerts influence on mitophagy through the ubiquitination of outer mitochondrial membrane proteins. Conversely, BNIP3/Nix and FUNDC1 modulate mitophagy through their interaction with LC3, while also displaying certain interrelationships with each other. In this comprehensive review, our objective is to investigate the intricate interplay between mitophagy and IR, elucidating the relevant signaling pathways and exploring the treatment strategies that have garnered attention in recent years. By assimilating and integrating these findings, we aim to establish a comprehensive understanding of the multifaceted roles and intricate mechanisms by which mitophagy influences IR. This endeavor, in turn, seeks to provide novel insights and serve as a catalyst for further research in the pursuit of innovative treatments targeting IR.

Objective To observe the clinical efficacy of"hegu needling"combined with"joint needling"in the treatment of chronic lumbar muscle strain.Methods A total of 64 patients with chronic lumbar muscle strain were randomly divided into observation group and control group,32 cases in each group.The control group was treated with routine acupuncture,and the observation group was treated with"hegu needling"combined with"joint needling"on the basis of the control group.One week for a course of treatment,a total of two courses of treatment.After two weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes of Visual Analogue Scale(VAS)of pain score and simplified Oswestry Dysfunction Index questionnaire(simplified ODI)score were observed before and after treatment.The changes of spinal mobility were compared before and after treatment between the two groups.Results(1)The total effective rate was 93.75%(30/32)in the observation group and 78.13%(25/32)in the control group.The curative effect of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the simplified ODI score and spinal activity score of the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the simplified ODI score and spinal activity score,the differences were statistically significant(P＜0.05).(3)After two weeks of treatment,the VAS scores of the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the VAS score,the difference was statistically significant(P＜0.05).After one month of treatment,there was no significant difference in VAS score of the observation group when compared with that after two weeks of treatment(P＞0.05).Conclusion"Hegu needling"combined with"joint needling"in the treatment of chronic lumbar muscle strain can significantly improve the patients'pain symptoms,enhance the patient's waist function,and improve the patients'spinal mobility.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.