Objective To study the bioequivalence of generic and original dapoxetine hydrochloride tablets in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.Fasting and fed tests were performed on 36 subjects each.Single oral dose 60 mg of test and reference pre parations were taken under fasting and fed conditions,respectively.Plasma concentration of dapoxetine was determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic(PK)parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main PK parameters of the test and reference preparations of dapoxetine tablets in the fasting group were as follows:Cmax were(449.36±203.01)and(432.85±199.75)ng·mL-1;AUC0-t were(2 400.96±1 392.58)and(2 251.82±1 225.84)ng·mL-1·h;AUC0-∞ were(2 529.94±1 498.05)and(2 371.06±1 305.22)ng·mL-1·h.The main PK parameters of the test and reference preparations of dapoxetine tablets in the fed group were as follows:Cmax were(651.29±179.38)and(672.83±249.42)ng·mL-1;AUC0-t were(3 391.27±1 358.73)and(3 314.56±1 360.39)ng·mL-1·h;AUC0-∞ were(3 630.79±1 605.89)and(3 549.22±1 526.61)ng·mL-1·h.Under the fasting and fed conditions,the 90％confidence intervals of the main PK parameters of the test and reference preparations of dapoxetine tablets are 80.00％-125.00％.Conclusion Under the fasting and fed conditions,a single oral dose of generic and original dapoxetine hydrochloride tablets in Chinese healthy adult volunteers showed bioequivalence.

Objective To study the bioequivalence of generic and original dapoxetine hydrochloride tablets in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.Fasting and fed tests were performed on 36 subjects each.Single oral dose 60 mg of test and reference pre parations were taken under fasting and fed conditions,respectively.Plasma concentration of dapoxetine was determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic(PK)parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main PK parameters of the test and reference preparations of dapoxetine tablets in the fasting group were as follows:Cmax were(449.36±203.01)and(432.85±199.75)ng·mL-1;AUC0-t were(2 400.96±1 392.58)and(2 251.82±1 225.84)ng·mL-1·h;AUC0-∞ were(2 529.94±1 498.05)and(2 371.06±1 305.22)ng·mL-1·h.The main PK parameters of the test and reference preparations of dapoxetine tablets in the fed group were as follows:Cmax were(651.29±179.38)and(672.83±249.42)ng·mL-1;AUC0-t were(3 391.27±1 358.73)and(3 314.56±1 360.39)ng·mL-1·h;AUC0-∞ were(3 630.79±1 605.89)and(3 549.22±1 526.61)ng·mL-1·h.Under the fasting and fed conditions,the 90％confidence intervals of the main PK parameters of the test and reference preparations of dapoxetine tablets are 80.00％-125.00％.Conclusion Under the fasting and fed conditions,a single oral dose of generic and original dapoxetine hydrochloride tablets in Chinese healthy adult volunteers showed bioequivalence.

Objective:To investigate the impact of retaining part of the urethral mucosa on postoperative urinary control,erec-tile function,and ejaculatory function in patients undergoing holmium laser enucleation of the prostate(HoLEP)surgery.Methods:A retrospective analysis was conducted on 176 benign prostatic hyperplasia(BPH)patients who underwent surgical treatment at our hospital from January 2019 to January 2022,including 80 cases of modified HoLEP surgery and 96 cases of standard HoLEP surgery.Preoperative and postoperative clinical data were collected and analyzed.Results:At 3 months postoperatively,both groups showed significant improvement in maximum flow rate(Qmax),International Prostate Symptom Score(IPSS),residual urine volume(RUV),and quality of life(QOL)compared to pre-treatment values,with statistically significant differences(P＜0.05).There was a sig-nificant difference in QOL scores between the experimental and control groups(P＜0.05).At 3 months postoperatively,the incidence of urinary incontinence was significantly lower in the experimental group compared to the control group(P＜0.05).At 6 months post-operatively,both groups showed a significant increase in International Index of Erectile Function-5(IIEF-5)scores compared to preop-erative values(P＜0.05),with no significant difference between the two groups.The incidence of retrograde ejaculation in the exper-imental group was significantly lower than that in the control group(P＜0.05).Conclusions:Retaining part of the urethral mucosa in HoLEP surgery can effectively treat BPH,providing significant advantages in terms of urinary control and playing a positive role in o-verall postoperative sexual function recovery.

ObjectiveTo improve the current standard of Belladonnae Herba in the 2020 edition of Chinese Pharmacopoeia. MethodTaking hyoscyamine sulfate， atropine sulfate and scopoletin as reference substances， and ethyl acetate-methanol-concentrated ammonia（17∶4∶2）as developing solvent， thin layer chromatography （TLC） was applied in the qualitative identification of Belladonnae Herba. The moisture， total ash and ethanol-soluble extract of Belladonnae Herba were determined based on the general principles in the 2020 edition of Chinese Pharmacopoeia （volume Ⅳ）. The contents of hyoscyamine sulfate and scopolamine hydrobromide were analyzed by high performance liquid chromatography （HPLC） with mobile phase of acetonitrile-54 mmol·L^-1 phosphate buffer solution （14∶86）， flow rate of 1.0 mL·min^-1 and detection wavelength at 210 nm. ResultThe spots in the TLC were clear with good separation and specificity. Hyoscyamine sulfate and scopolamine hydrobromide showed a good linearity with peak area in the range of 0.024 7-0.789 6 g·L^-1 （r=0.999 9） and 0.003 9-0.124 0 g·L^-1 （r=0.999 9）， the average recoveries of these two ingredients were 100.29% （RSD 1.6%） and 99.04% （RSD 1.4%）， respectively. The limits for moisture， total ash in Belladonnae Herba should be less than 13.0% and the limit for the ethanol-soluble extract should be more than 10.0%. Due to the low content and wide variation of scopolamine hydrobromide， the content of hyoscyamine sulfate should not be less than 0.098%. ConclusionThe established method is simple， specific and reproducible， which can be used to improve the quality control standard of Belladonnae Herba.

Histone lysine-specific demethylase 1(LSD1) has become a promising molecular target for lung cancer therapy. Upon the screening platform for LSD1 activity, some Chinese herbal extracts were screened for LSD1 activity inhibition, and the underlying mechanism was preliminarily investigated at both molecular and cellular levels. The results of LSD1 inhibition showed that Puerariae Lobatae Radix extract can effectively reduce LSD1 expression to elevate the expression of H3 K4 me2 and H3 K9 me2 substrates in H1975 and H1299 cells. Furthermore, Puerariae Lobatae Radix was evaluated for its anti-lung cancer activity. It had a potent inhibitory ability against the proliferation and colony formation of both H1975 and H1299 cells. Flow cytometry and DAPI staining assays indicated that Puerariae Lobatae Radix can induce the apoptosis of lung cancer cells. In addition, it can significantly suppress the migration and reverse the epithelial-mesenchymal transition(EMT) process of lung cancer cells by activating E-cadherin and suppressing the expression of N-cadherin, slug and vimentin. To sum up, Puerariae Lobatae Radix displayed a robust inhibitory activity against lung cancer, and the mechanism may be related to the down-regulation of LSD1 expression to induce the cell apoptosis and suppress the cell migration and EMT process. These findings will provide new insights into the action of Puerariae Lobatae Radix as an anti-lung cancer agent and offer new ideas for the study on the anti-cancer action of Chinese medicine based on the epigenetic modification.
Pueraria/chemistry* ; Histone Demethylases/analysis* ; Plant Roots/chemistry* ; Epithelial-Mesenchymal Transition ; Neoplasms

Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E₂ and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E₂ levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.
AMP-Activated Protein Kinases ; Animals ; Cyclin D2 ; Female ; Follicle Stimulating Hormone/therapeutic use* ; Humans ; Luteinizing Hormone/therapeutic use* ; Metformin/pharmacology* ; Mice ; Mice, Inbred C57BL ; Oogonial Stem Cells/metabolism* ; Ovarian Cysts/drug therapy* ; Ovarian Neoplasms ; Polycystic Ovary Syndrome/drug therapy* ; Proliferating Cell Nuclear Antigen/therapeutic use* ; TOR Serine-Threonine Kinases

OBJECTIVE: To evaluate the existing randomized controlled trials (RCTs) for evidence of the efficacy and safety of head acupuncture (HA) plus Schuell's language rehabilitation (SLR) in post-stroke aphasia. METHODS: Seven databases including Embase, PubMed, Cochrane Library, Technology Periodical Database, the China National Knowledge Infrastructure, SinoMed and Wanfang Data Information Site were searched for RCTs published from database inception until November 14, 2021. RCTs that compared HA plus SLR with sham (or blank) control, acupuncture therapy alone, certain language rehabilitation therapy alone or other therapies for post-stroke aphasia were included. Data were extracted and assessed, and the quality of RCTs was evaluated. Fixed-effects model was used, with meta-inflfluence analysis, meta-regression, and regression-based sub-group analyses applied for exploration of heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 32 RCTs with 1,968 patients were included and 51 comparisons were conducted classified as types of strokes and aphasia. (1) For patients with aphasia after ischemic stroke, HA plus PSA showed significantly higher accumulative markedly effective rate [relative risk (RR)=1.55, 95% confidence interval (CI): 1.19-2.02, I²=0%] and accumulative effective rate (RR=1.22, 95% CI: 1.09-1.36, I²=0%). (2) For patients with comprehensive types of stroke, HA plus PSA was more effective in increasing recovery rate (RR=1.89, 95% CI: 1.39-2.56, I²=0%), accumulative markedly effective rate (RR=1.53, 95% CI: 1.36-1.72, I²=9%) and accumulative effective rate (RR=1.14, 95% CI: 1.09-1.19, I²=34%). (3) For patients with aphasia after stroke, HA plus PSA was superior to PSA alone with statistical significance in increasing recovery rate (RR=2.08, 95% CI: 1.24-3.46, I²=0%), accumulative markedly effective rate (RR=1.49, 95% CI: 1.24-1.78, I²=0%) and accumulative effective rate (RR=1.15, 95% CI: 1.06-1.24, I²=39%). (4) For patients with multiple types of aphasia, HA plus PSA also demonstrated significantly higher recovery rate (RR=1.86, 95% CI: 1.28-2.72, I²=0%), accumulative markedly effective rate (RR=1.55, 95% CI: 1.35-1.78, I²=22%), and accumulative effective rate (RR=1.17, 95% CI: 1.11-1.23, I²=41%). (5) For patients with motor aphasia after ischemic stroke, compared with PSA alone, HA plus PSA showed significantly higher accumulative markedly effective rate (RR=1.38, 95% CI: 1.06-1.79, I²=0%) and accumulative effective rate (RR=1.20, 95% CI: 1.05-1.37, I²=0%). Meta-regression analyses were performed without significant difference, and publication bias was found in some comparisons. CONCLUSION HA plus SLR was significantly associated with better language ability and higher effective rate for patients with post-stroke aphasia, and HA should be operated cautiously especially during acupuncture at eye and neck. (Registration No. CRD42020154475).
Acupuncture Therapy ; Aphasia/rehabilitation* ; Humans ; Ischemic Stroke ; Language ; Prostate-Specific Antigen ; Randomized Controlled Trials as Topic ; Stroke/therapy*

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

OBJECTIVE: To explore the effect of intermittent pneumatic compression(IPC) combined with 3M thermometer on the prevention of deep venous thrombosis(DVT) in patients with femoral intertrochanteric fracture. METHODS: From March 2016 to August 2019, 127 patients with femoral intertrochanteric fractures who underwent proximal femoral nail antirotation(PFNA) were retrospectively analyzed. They were divided into two groups according to different methods of thrombus prevention and treatment. Among them, 63 patients in group A did not use IPC and 3M thermometer;64 cases in group B were treated with IPC combined with 3M thermometer. Color Doppler ultrasound was used to dynamically monitor the DVT and changes of lower limbs during perioperative period. The venous thrombosis of lower limbs was monitored at 0, 24, 72 h and > 72 h after operation(recheck every 3 days until discharge). RESULTS: Occurrence of DVT of lower limbs after PFNA operation in two groups:there were 5 cases (7.8%) in group B and 20 cases (31.7%) in group A, there was significant difference between two groups (P=0.001). There was no significant difference in lower limb DVT between two groups at 0, 72 and > 72 h after operation(P>0.05), but the formation rate of group A was significantly higher than that of group B at 24 h after operation (P=0.049). There was no significant difference in DVT formation between group A and group B(P>0.05). However, the formation of DVT in group A was significantly higher than that in group B(P=0.012). CONCLUSION Intraoperative IPC combined with 3M thermostat can effectively prevent DVT of lower limbs in patients undergoing PFNA surgery.
Femoral Fractures/surgery* ; Fracture Fixation, Intramedullary/methods* ; Hip Fractures/surgery* ; Humans ; Lower Extremity/surgery* ; Retrospective Studies ; Venous Thrombosis/prevention & control*

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.
Biomedical Research ; Clinical Trials as Topic ; Consensus ; Drugs, Chinese Herbal ; Ethical Review ; Humans ; Medicine, Chinese Traditional ; Multicenter Studies as Topic ; Pharmaceutical Preparations