Aim To observe the mechanism of salvian-olic acid B(SalB)against oxygen glucose deprivation/re-oxygenation(OGD/R)injury in H9c2 cardiomyo-cytes.Methods The protective concentration of SalB against OGD/R-injured H9c2 cardiomyocytes was screened by CCK-8 assay.The levels of lactate dehy-drogenase(LDH),aspartate transaminase(AST)and creatine kinase(CK)were detected by ELISA kit.The mechanism of action of SalB on OGD/R-injured H9c2 cardiomyocytes was explored using high-through-put sequencing of the transcriptome.The binding of SalB to differential proteins was assessed using molecu-lar docking assays.Fatty acid content was determined using free fatty acid kits.The relative expressions of mRNA and protein of differential genes were verified by RT-qPCR and Western blot.The causal relationship between the target of action of SalB and heart failure was examined by Mendelian randomization experiment.Results SalB protected OGD/R-injured H9c2 cardio-myocytes and significantly reduced the levels of CK,LDH and AST compared with the blank control group.One hundred differential genes were screened by tran-scriptome sequencing,which were mainly involved in fatty acid elongation,central carbon metabolism of cancer,tryptophan metabolism pathways.Molecular docking showed that SalB had good binding energy to differential proteins.The mRNA and protein expression of core differential genes Elovl6,Echs1 and Acot1 were consistent with the transcriptome sequencing results.SalB reduced fatty acidsafter OGD/R injury.Mende-lian randomization experiments suggested that SalB might reduce the risk of heart failure through fatty acid metabolism,thereby reducing the risk of heart failure.Conclusion SalB can protect H9c2 cardiomyocytes after OGD/R injury by down-regulating Elovl6,Echs1 and Acot1 expression through the fatty acid metabolism pathway.

Objective To analyze the risk factors of fluconazole resistance in Candida tropicalis(C.tropicalis)urinary tract infection(UTI),and evaluate the efficacy of different treatment regimens.Methods Patients with C.tropicalis UTI at Xiangya Hospital of Central South University from January 2021 to December 2023 were in-cluded for single center retrospective study.The minimum inhibitory concentration(MIC)of fluconazole was deter-mined by microbroth dilution.Patients were divided into a fluconazole-resistant group and a fluconazole-sensitive group based on fluconazole resistance.Risk factors for fluconazole resistance were analyzed based on clinical data,and therapeutic efficacy in patients in fluconazole-resistant group was analyzed.Results A total of 198 patients were included in the study.133(67.2％)C.tropicalis strains were detected to be sensitive to fluconazole,while 65(32.8％)strains were resistant,and 63.1％(n=41)had MIC values ≥128 μg/mL.Compared with fluconazole-sensitive group,fluconazole-resistant group had a higher proportion of pulmonary infection(P=0.019).Pulmonary infection(OR=3.282)was a risk factor for fluconazole resistance in C.tropicalis UTI,while urinary system ob-struction(OR=0.269)was a protective factor for fluconazole resistance in C.tropicalis UTI.There was no statis-tically significant difference in the usage rate of different antimicrobial agent types between the two groups(all P＞0.05).The therapeutic efficacy analysis showed that the effective rates of treatment with fluconazole dosage regi-mens of ≤200 mg/d,≥400 mg/d,and fluconazole monotherapy against fluconazole-resistant strains were 66.7％(6/9),83.3％(5/6),and 100％(6/6),respectively.For patients treated with monotherapy using other drugs or with multidrug sequential treatment regimens,the treatment effective rate was 60.0％(3/5).The proportion of pa-tients in the effective treatment group who removed their urinary catheters after detecting C.tropicalis was higher than that in the ineffective treatment group(P＜0.001).Conclusion The fluconazole resistance of C.tropicalis is related to urinary tract obstruction and concurrent pulmonary infection.When treating UTI caused by fluconazole-resistant strains,the catheter should be removed as early as possible.In addition to increasing the dosage of flucon-azole,other antifungal drugs such as flucytosine alone or sequential treatment with multiple drugs can also be con-sidered.

Objective:To explore the hemodynamic characteristics of the middle cerebral artery (MCA) in atherosclerotic stenosis using four-dimensional flow (4D Flow) MRI, and combining high-resolution magnetic resonance vessel wall imaging (HR VW-MRI) to analyze the relationship between hemodynamics and the degree of stenosis, as well as the morphological characteristics of plaques.Methods:The study was a cross-sectional study. A total of 24 patients with middle cerebral artery(MCA) M1 atherosclerotic stenosis and 10 age and sex matched healthy controls (HC group) were prospectively recruited from September 2018 to March 2021 at Beijing Tiantan Hospital, Capital Medical University. All subjects underwent MRI examination. The hemodynamic of MCA were collected by 4D Flow MRI, and the hemodynamic parameters of proximal and distal MCA stenosis were calculated by blood flow post-processing software, including average blood flow rate (FR avg), average blood flow velocity (V avg), peak blood flow velocity (V pk), time average wall shear stress (TAWSS), minimum wall shear stress (WSS min) and oscillatory shear index (OSI). The differences in hemodynamic parameters among the proximal and distal ends of MCA stenosis and the HC group were compared using one-way ANOVA or Kruskal-Wallis H test. The stenosis rate and characteristics of MCA plaque were analyzed by HR VW-MRI, including remodeling index (RI), normalized wall index (NWI) and plaque length. Pearson or Spearman correlation analysis was used to explore the correlation between stenosis rate and hemodynamic parameters. Taking the stenosis rate as the control variable, partial correlation analysis was used to explore the correlation between plaque morphological characteristics and hemodynamic parameters. Results:There were statistically significant differences in FR avg, V avg, V pk, TAWSS, OSI, WSS min among the proximal and distal stenosis of MCA and HC groups ( P<0.05). The proximal end of the MCA stenosis had significantly higher FR avg, V avg, TAWSS and WSS min than those of the distal end of the stenosis ( P<0.01). The FR avg, V avg, V pk, TAWSS, and WSS min in the distal end of MCA stenosis were lower than those in the HC group, while the OSI was higher than that in the HC group ( P<0.01). The correlation analysis results showed that the MCA proximal V pk ( r=-0.425, P=0.027) and distal V pk ( r=-0.538, P=0.004) were negatively correlated with the diameter stenosis rate. When the stenosis rate was taken as the control factor, in the MCA proximal stenosis, V avg ( r=0.553, P=0.003), TAWSS ( r=0.543, P=0.004) and WSS min ( r=0.547, P=0.004) were positively correlated with RI, proximal OSI was negatively correlated with RI ( r=-0.492, P=0.011), and was positively correlated with the plaque length ( r=0.437, P=0.026). At the distal end of the stenosis, V pk was negatively correlated with NWI ( r=-0.556, P=0.003), OSI was negatively correlated with RI ( r=-0.511, P=0.008), NWI ( r=-0.390, P=0.049). TAWSS was positively correlated with RI ( r=0.393, P=0.047). Conclusions:The 4D Flow MRI demonstrates characteristic hemodynamic changes in the proximal and distal ends of the stenotic MCA. The local hemodynamic characteristics of the stenotic MCA are correlated with plaque morphological parameters, including lumen stenosis, plaque load, and RI. It suggests an interaction between the occurrence and development of MCA plaque and local hemodynamic changes.

Objective To analyze the risk factors of fluconazole resistance in Candida tropicalis(C.tropicalis)urinary tract infection(UTI),and evaluate the efficacy of different treatment regimens.Methods Patients with C.tropicalis UTI at Xiangya Hospital of Central South University from January 2021 to December 2023 were in-cluded for single center retrospective study.The minimum inhibitory concentration(MIC)of fluconazole was deter-mined by microbroth dilution.Patients were divided into a fluconazole-resistant group and a fluconazole-sensitive group based on fluconazole resistance.Risk factors for fluconazole resistance were analyzed based on clinical data,and therapeutic efficacy in patients in fluconazole-resistant group was analyzed.Results A total of 198 patients were included in the study.133(67.2％)C.tropicalis strains were detected to be sensitive to fluconazole,while 65(32.8％)strains were resistant,and 63.1％(n=41)had MIC values ≥128 μg/mL.Compared with fluconazole-sensitive group,fluconazole-resistant group had a higher proportion of pulmonary infection(P=0.019).Pulmonary infection(OR=3.282)was a risk factor for fluconazole resistance in C.tropicalis UTI,while urinary system ob-struction(OR=0.269)was a protective factor for fluconazole resistance in C.tropicalis UTI.There was no statis-tically significant difference in the usage rate of different antimicrobial agent types between the two groups(all P＞0.05).The therapeutic efficacy analysis showed that the effective rates of treatment with fluconazole dosage regi-mens of ≤200 mg/d,≥400 mg/d,and fluconazole monotherapy against fluconazole-resistant strains were 66.7％(6/9),83.3％(5/6),and 100％(6/6),respectively.For patients treated with monotherapy using other drugs or with multidrug sequential treatment regimens,the treatment effective rate was 60.0％(3/5).The proportion of pa-tients in the effective treatment group who removed their urinary catheters after detecting C.tropicalis was higher than that in the ineffective treatment group(P＜0.001).Conclusion The fluconazole resistance of C.tropicalis is related to urinary tract obstruction and concurrent pulmonary infection.When treating UTI caused by fluconazole-resistant strains,the catheter should be removed as early as possible.In addition to increasing the dosage of flucon-azole,other antifungal drugs such as flucytosine alone or sequential treatment with multiple drugs can also be con-sidered.

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.

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

Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

Objective:To investigate the therapeutic value of visual endoscopic retrograde appendicitis therapy (vERAT) in pediatric patients with acute suppurative appendicitis (ASA).Methods:This was a retrospective cohort study. A total of 55 ASA patients who underwent vERAT at the Pediatric Department of the Tangdu Hospital of Air Force Medical University between November 2023 and January 2025 were selected and divided into groups based on the presence or absence of fecaliths: fecalith group and non-fecalith group. The baseline characteristics, initial treatment success rates, treatment costs, hospital stay duration, procedure time, and recurrence rates between two groups were compared. Mann-Whitney U test and χ2 test were used to evaluate group differences. Results:A total of 55 ASA patients were enrolled, including 38 males and 17 females, with the age of 11.2 (9.2, 13.1) years. Based on the presence of fecaliths, patients were divided into two groups: fecalith group (32 cases) and non-fecalith group (23 cases). No statistically significant differences were observed between the two groups in terms of age, gender, duration of abdominal pain, white blood cell count, neutrophil percentage, diameter of appendix, thickness of appendix clinical symptoms or signs (all P>0.05). The initial treatment success rates were 91% (29/32) in fecalith group and 96% (22/23) in non-fecalith group, with no statistically significant difference ( P=0.632). However, significant differences were noted in stent placement ( χ2=5.85, P=0.026) and procedure time ( Z=4.75, P<0.001). The follow-up duration time was 6.0 (2.0, 12.0) and 7.0 (2.0, 8.5) months for the fecalith and non-fecalith groups, respectively, with no significant difference ( Z=0.05, P=0.962). The recurrence rates were 14% (4/29) in fecalith group and 5% (1/22) in non-fecalith group, with no statistically significant difference ( P=0.375). Conclusions:vERAT can safely and effectively treat pediatric ASA, regardless of the presence or absence of fecaliths. It can provide a new treatment option for ASA.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.