In this comprehensive review, we delve into the evolution of drug delivery systems in reproductive medicine with a focus on the emerging role of exosomes, a class of extracellular vesicles. Exosomes offer unique advantages in overcoming these challenges due to their inherent biocompatibility, stability, and ability to facilitate targeted delivery. This review provides a detailed examination of exosome biogenesis and their function in cellular communication, setting the stage for understanding their potential as drug delivery vehicles. We explore the mechanisms through which exosomes can be loaded with small molecule drugs and the benefits they offer over synthetic nanoparticles. The review highlights groundbreaking case studies that illustrate the successful application of exosome-mediated drug delivery in reproductive health, including enhancing fertility treatments, supporting gamete and embryo development, and facilitating maternal-fetal communication. This study aims to provide a precise understanding of how exosomal drug delivery can revolutionize treatments for reproductive health disorders, paving the way for future therapeutic applications. Lastly, we touch upon the promising therapeutic implications of exosomal delivery for proteins and genes, offering a window into future treatments for reproductive health disorders.

Acupuncture is an ancient treatment method used in traditional Chinese medicine and has been popularized worldwide. Over the past decade, there has been an increase in the amount of acupuncture research, mostly comprised of randomized controlled trials (RCTs) that aimed to answer the question on the efficacy of acupuncture. However, poor methodology and low replicability in these acupuncture RCTs have resulted in uncertainty about the efficacy of acupuncture. In this review, current advancements and challenges in acupuncture RCTs, regarding the methodological aspects of randomization, blinding, sham acupuncture and quality of reporting, were discussed. While there have been advancements in various aspects, current acupuncture RCTs still face pressing issues such as inadequate randomization and blinding, unviable sham acupuncture controls, and poor reporting quality. Given these limitations, this review seeks to identify the methodological problems that are responsible for these problems and to suggest solutions that could help to overcome them so as to improve the quality of future studies evaluating the efficacy of acupuncture. Please cite this article as: Seetoh WS, Lim RQR, Xu RB, Sun MX, Zhang P, Wang MN. Advancements and challenges of acupuncture randomized controlled trials. J Integr Med. 2025; 23(4): 333-343.
Acupuncture Therapy ; Humans ; Randomized Controlled Trials as Topic/methods* ; Research Design

Objective To investigate the effect of pneumoperitoneum pressure during robotic-assisted kidney transplantation (RAKT) on the function of the transplant kidney. Methods The data of 243 kidney transplant recipients were retrospectively analyzed and divided into open kidney transplantation (OKT) group (n=105) and RAKT group (n=138). The RAKT group was further divided into 13 mmHg group (n=67) and 7 mmHg group (n=71) based on pneumoperitoneum pressure. The donor information, recipient's preoperative general data, intraoperative data, and postoperative recovery of the three groups were compared. In the RAKT group, the renal artery, segmental artery, interlobar artery, and venous flow velocity of the transplant kidney were measured using laparoscopic ultrasound. Results There was a statistically significant difference in donor types among the groups (P<0.05), while other donor information and recipient's preoperative general data showed no statistically significant differences (all P>0.05). There were no statistically significant differences in serum creatinine and complications at 30 days and 1 year postoperatively among the groups (all P>0.05). The OKT group and 7 mmHg group had more intraoperative urine output than the 13 mmHg group. Both RAKT groups had less intraoperative blood loss and shorter hospital stays than the OKT group, and longer operation times than the OKT group (all P<0.05). There were no statistically significant differences in operation time, intraoperative blood loss, and hospital stay between the two RAKT groups (all P>0.05). The vascular flow velocity of the transplant kidney decreased at 13 mmHg compared to 7 mmHg pneumoperitoneum pressure, but the differences were not statistically significant (all P>0.05). Conclusions Controllable pneumoperitoneum pressure has a limited impact on the vascular flow velocity of the transplanted kidney. RAKT is a safe and effective surgical method under appropriate pneumoperitoneum pressure, and choosing a lower pneumoperitoneum pressure is more conducive to the early recovery of renal function postoperatively.

BACKGROUND:As a common disease in middle-aged and elderly,osteoarthritis is difficult to cure,and the pathogenesis is not clear.Long non-coding RNA participates in the pathogenesis of osteoarthritis through many ways,such as regulating translation,promoting or inhibiting mRNA,and adsorbing miRNAs. OBJECTIVE:To review the types of common long non-coding RNA in osteoarthritis,and the influence of multiple long non-coding RNAs on the pathological factors related to osteoarthritis,to analyze the future application of long non-coding RNAs in osteoarthritis. METHODS:Literature retrieval was conducted in CNKI,WanFang Data,VIP database,PubMed,Web of Science and Sciencedirect databases,using the search terms of"osteoarthritis,degenerative joint disease,degenerative arthritis,OA,LncRNA,long non-coding RNA,long noncoding RNA,long intergenic non-coding RNA"in Chinese and English.All relevant literature published from 1976 and May 2024 was retrieved.After literature screening,induction,analysis and summary,93 articles were finally included for review. RESULTS AND CONCLUSION:This review collected 25 long non-coding RNAs that are well studied with osteoarthritis.Long non-coding RNAs,as a molecular sponge for miRNA,are competing endogenous RNAs to competitively adsorb miRNAs and then affect downstream targets.Long non-coding RNAs can regulate physiopathological processes such as chondrocyte apoptosis and proliferation,cartilage extracellular matrix degradation,and inflammatory responses.Long non-coding RNAs are expected to become a biomarker and potential therapeutic target for the clinical diagnosis and therapeutic prognosis of osteoarthritis,and it may become a new strategy for the clinical treatment of osteoarthritis in the future.

Objective To report a rare clinical case of Rickettsia sibirica infection complicated with left ventricular apical thrombus,and to explore its pathogenesis,diagnosis and treatment strategies,as well as the significance of anticoagulant intervention.Methods Clinical analysis was performed on a 71-year-old female patient.The patient presented with fever,coma,and multiple organ damage.Combined with the presence of eschar on the left ankle and a history of contact with pet dogs,the diagnosis of Rickettsia sibirica infection was confirmed by blood metagenomic next-generation sequencing(mNGS).The patient was treated with doxycycline combined with vancomycin for anti-infection,and rivaroxaban for anticoagulation.Inflammatory indicators,coagulation function,cardiac ultrasound,and organ function were dynamically monitored.Results Blood mNGS detected Rickettsia sibirica(11 sequences,relative abundance 29.73%).The diagnosis was confirmed in combination with eschar,skin rash,and shock manifestations.After 4 days of anti-rickettsial treatment,the patient regained consciousness,body temperature and blood pressure returned to normal,and inflammatory and coagulation indicators improved significantly.Cardiac ultrasound showed a left ventricular apical thrombus(3.8 cm×2.4 cm).The thrombus persisted but remained asymptomatic after anticoagulant treatment.Rickettsia-induced vascular endothelial damage,hypercoagulable state,and reduced left ventricular systolic function[ejection fraction(EF)was 0.40]collectively contributed to the formation of the apical thrombus.Conclusions Rickettsia sibirica infection can lead to intracardiac thrombus(the first reported case),with mechanisms related to endothelial damage,hypercoagulable state,and cardiac insufficiency.mNGS has key value in the rapid identification of pathogens in patients with fever of unknown origin accompanied by shock.Doxycycline is a core effective drug for rickettsial infections,and early anticoagulant intervention is required for patients with complicated thrombus.A history of pet contact and skin eschar are important epidemiological clues,which need to be strengthened in clinical identification.

Objective To analyze the stimulation parameters and acupoint selection law of electroacupuncture in the treatment of cervical spondylotic radiculopathy(CSR)through data mining.Methods The clinical research literature about electroacupuncture in the treatment of CSR was retrieved from CNKI,Wanfang Data,VIP,PubMed and Web of Science from the establishment of the databases to September 2024.According to the inclusion and exclusion criteria,the literature was screened and the stimulation parameters and acupoint prescriptions were extracted.The association rule analysis was performed using SPSS Moderler 18.0 software,and clustering analysis was performed using SPSS Statistics 27.0 software.Results A total of 122 acupoint selection prescriptions for electroacupuncture treatment of CSR were extracted.The most commonly used stimulation parameters in electroacupuncture treatment of CSR were 2 Hz of continuous wave,2/100 Hz of dilatational wave,intensity tolerance,30 min/time,1 time/day,10 times/course,and a total of 20 treatments.The top 3 most commonly used acupoints were Jingjiaji,Houxi(SI3)and Fengchi(GB20);the meridians of acupoints were mainly the large intestine meridian,small intestine meridian and gallbladder meridian;the core prescription of association rule analysis was"Jingjiaji,Houxi,Quchi,Fengchi,Jianjing,Waiguan,Tianzhu,Hegu,Dazhui",and the acupoint combination with the highest support was"Jingjiaji-Houxi".5 clusters were obtained through clustering analysis.Conclusion In electroacupuncture treatment for CSR,the selection of acupoints is primarily aimed at unblocking meridians to relieve pain and nourishing the liver and kidney.The core acupoints group is Jingjiaji-Houxi;the stimulation parameters demonstrate a certain degree of regularity and clustering,primarily consisting of low-frequency continuous wave and alternating density wave of low and high frequencies.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

ObjectiveTo explore the effect of Yishen Tongluo prescription on sperm DNA fragmentation index （DFI） and sperm mitochondrial membrane potential （MMP） in patients with asymptomatic idiopathic asthenospermia infertility. MethodsA total of 128 patients with asymptomatic idiopathic asthenospermia were randomly assigned to an experimental group （64 cases） and a control group （64 cases）. The experimental group received Yishen Tongluo prescription， while the control group was treated with Wuzi Yanzongwan combined with L-carnitine oral solution. One treatment course lasted 12 weeks. Spouse pregnancy rate， sperm progressive motility （PR）， total sperm motility （PR+NP）， sperm function （sperm tail hypotonic swelling rate， sperm acrosin activity）， sperm DFI， and sperm MMP were compared between the two groups before and after treatment. Adverse reactions were observed and recorded during the study， and clinical efficacy and safety were systematically evaluated. ResultsA total of 121 patients completed the study， including 61 in the experimental group and 60 in the control group. The spouse pregnancy rate in the experimental group was 14.75% （9/61）， higher than that in the control group at 6.67% （4/60）， though the difference was not statistically significant. Clinical efficacy in the experimental group was superior to that in the control group （P<0.05）. Compared with the results before treatment， sperm PR， PR + NP， sperm tail hypotonic swelling rate， sperm acrosin activity， sperm DFI， and sperm MMP were significantly improved in both groups after treatment （P<0.05）， with greater improvements in the experimental group （P<0.05）. However， there was no significant change in sperm concentration in either group after treatment. During the study， no abnormal safety indicators or significant adverse reactions occurred in either group. ConclusionThe kidney-tonifying and collateral-dredging method shows good clinical efficacy in the treatment of asymptomatic idiopathic asthenospermia infertility. Yishen Tongluo prescription can improve sperm motility， increase spouse pregnancy rate， enhance sperm function， and demonstrates good safety. Its mechanism may be related to reducing sperm DFI and increasing sperm MMP.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.