Polycystic ovary syndrome(PCOS)is clinically characterized by insulin resistance,ovulatory dysfunction and hyperandrogenemia,often accompanied by obesity,type 2 diabetes,and dyslipidemia.This article reviews the recent studies on the intervention of PCOS with herbal medicines,including traditional Chinese medicine(TCM)compound formulas and single active compounds.The results demonstrate that both TCM compound formulas and single active compounds are effective on improving PCOS symptoms,with the advantages of multi-target actions and personalized treatment.TCM compound formulas for PCOS can be categorized into kidney-tonifying formulas(e.g.,Antai Fanglou Decoction,Gui Zhu Yikun Formula,Liuwei Dihuang Pills,Bushen Huayu Formula),phlegm-resolving formulas(e.g.,Cang Fu Daotan Decoction,Erchen Decoction),liver-soothing formulas(e.g.,Xiaoyao San,Shaoyao Gancao Decoction),and blood-activating formulas(e.g.,Jiawei Shaoyao Gancao Decoction,Gexia Zhuyu Decoction,Huayu Xiaozheng Decoction).These compound formulas separately exhibit actions of tonifying kidney essence,soothing liver and relieving depression,and activating blood circulation to resolve stasis,which are aligned with the TCM etiology and pathogenesis of PCOS.Single active compounds from herbal medicine primarily include flavonoids,alkaloids,terpenoids and polyphenols.Extractives from herbal medicines exert therapeutic effects by inhibiting ovarian inflammatory responses and relieveing hyperandrogenemia insulin resistance.Key signaling pathways for the intervention of PCOS with TCM include PI3K/AKT/mTOR,SIRT1/AMPK,TLR4/NF-κB,IRS1/PI3K/GLUT4,RIP1/RIP3/MLKL,HMGB1/RAGE,and Hippo-YAP.The review of recent advances in TCM formulas and single active compounds for the treatment of PCOS along with their underlying mechanisms will provide valuable insights for clinical management and new drug development for PCOS.

Objective To explore the regulatory role of N-methyl berbamine(N-MB)in intracellular calcium homeostasis in H9c2 car-diomyocytes,and,thereby,clarify the possible mechanism of the myocardial protective effect of N-MB.Methods Binding of N-MB to CaV1.2 channels was simulated using the MOE software,and the binding affinity and binding mode were determined.The hCaV1.2 gene was transfected into HEK293 cells,and the effect of N-MB(30 μmol/L)on the CaV1.2 current was detected using the whole-cell patch clamp technique.In addition,a Fluo 3-AM fluorescent probe was loaded into H9c2 cardiomyocytes,and the effect of N-MB(3,30 μmol/L)on intracellular calcium ion concentration was observed under a laser confocal microscope.The effect of N-MB(3,30 μmol/L)on the expression of Ca2+regulation-related genes Cacna1c,Cacnb2,Ryr2,Serca2a,and Ncx1 in H9c2 cardiomyocytes was examined using real-time quantitative PCR.Results N-MB was predicted to bind to CaV1.2 channels.The binding sites mainly involved Phe1191,Thr1420,and Asn771,and the binding modes were H-donor,pi-pi,and pi-H.N-MB(30 μmol/L)significantly inhibited CaV1.2 currents,with an inhibition rate of 76.09％±7.41％.The fluorescence intensity of intracellular Ca2+level in H9c2 cardiomyocytes was significantly enhanced with N-MB treatment(3,30 μmol/L,P＜0.01).Compared with the control group,differences in the expression of Cacna1c,Serca2a,and Ncx1 in H9c2 cardiomyocytes were not significant after N-MB(3,30 μmol/L)intervention(P＞0.05),whereas the expression of Cacnb2 significantly reduced(P＜0.001)and the expression of Ryr2 significantly increased(P＜0.05).Conclusion N-MB binds to CaV1.2 calcium channels.N-MB may regulate intracellular calcium homeostasis by inhibiting calcium currents by decreasing the gene expression of CaV1.2 calcium channels.Additionally,N-MB may also increase intracellular Ca2+concentration by promoting the expression of Ryr2,which could be the mechanism underlying the myocardial protective effect of N-MB.

OBJECTIVE To provide a reference for standardizing the conduct of positron-emitting radiopharmaceuticals'phase 0 clinical trials(hereinafter referred to as"phase 0 clinical trials")and advancing the development of innovative drug by medical institutions.METHODS Initiated by the First Affiliated Hospital of Jinan University,a panel of experts consisting of pharmacy,clinical medicine and medical ethics from multiple institutions was established to investigate the current landscape,and discuss the necessary conditions,procedures,and other aspects for conducting phase 0 clinical trials in medical institutions by integrating relevant national policies,regulations and expert consensus.Finally,an agreement was reached to formulate this consensus.RESULTS&CONCLUSIONS Currently,most medical institutions have deficiencies in pharmaceutical care during the management of radiopharmaceuticals and the phase 0 clinical trials.In conjunction with the Expert Consensus on the Establishment of Nuclear Pharmacist Positions,this consensus explicitly defines the responsibilities of nuclear pharmacists in the phase 0 clinical trials on the basis of the Expert Consensus for the Application of Positron Emission Tomography Radioligands for Translational Study in the Phase 0 Clinical Trials(2020 edition),providing a guidance for high-quality participation of nuclear pharmacists from medical institutions in China in phase 0 clinical research.Additionally,in consideration of some constraints imposed by current relevant regulations,this consensus also proposes strategic recommendations,such as encouraging medical institutions to form a consortium,leading to the establishment of dedicated bases or industrial parks,holding significant implications to strengthen institutional capacity for advancing radiopharmaceutical innovation through phase 0 clinical trials.

Objective To explore the regulatory role of N-methyl berbamine(N-MB)in intracellular calcium homeostasis in H9c2 car-diomyocytes,and,thereby,clarify the possible mechanism of the myocardial protective effect of N-MB.Methods Binding of N-MB to CaV1.2 channels was simulated using the MOE software,and the binding affinity and binding mode were determined.The hCaV1.2 gene was transfected into HEK293 cells,and the effect of N-MB(30 μmol/L)on the CaV1.2 current was detected using the whole-cell patch clamp technique.In addition,a Fluo 3-AM fluorescent probe was loaded into H9c2 cardiomyocytes,and the effect of N-MB(3,30 μmol/L)on intracellular calcium ion concentration was observed under a laser confocal microscope.The effect of N-MB(3,30 μmol/L)on the expression of Ca2+regulation-related genes Cacna1c,Cacnb2,Ryr2,Serca2a,and Ncx1 in H9c2 cardiomyocytes was examined using real-time quantitative PCR.Results N-MB was predicted to bind to CaV1.2 channels.The binding sites mainly involved Phe1191,Thr1420,and Asn771,and the binding modes were H-donor,pi-pi,and pi-H.N-MB(30 μmol/L)significantly inhibited CaV1.2 currents,with an inhibition rate of 76.09％±7.41％.The fluorescence intensity of intracellular Ca2+level in H9c2 cardiomyocytes was significantly enhanced with N-MB treatment(3,30 μmol/L,P＜0.01).Compared with the control group,differences in the expression of Cacna1c,Serca2a,and Ncx1 in H9c2 cardiomyocytes were not significant after N-MB(3,30 μmol/L)intervention(P＞0.05),whereas the expression of Cacnb2 significantly reduced(P＜0.001)and the expression of Ryr2 significantly increased(P＜0.05).Conclusion N-MB binds to CaV1.2 calcium channels.N-MB may regulate intracellular calcium homeostasis by inhibiting calcium currents by decreasing the gene expression of CaV1.2 calcium channels.Additionally,N-MB may also increase intracellular Ca2+concentration by promoting the expression of Ryr2,which could be the mechanism underlying the myocardial protective effect of N-MB.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Click chemistry has been proven to be very useful in drug delivery. Due to the availability of a large number of click reactions with a various characteristics, selection of appropriate chemistry for a given application is often not a trivial task. This review is written for pharmaceutical researchers who are interested in click chemistry applications and yet may not be click chemistry experts. For this, the review gives an overview of available click reactions organized by application types. Further, the general understanding of click reactions being fast and high yielding sometimes overshadows the need to analyze reaction kinetics in assessing suitability of a given reaction for certain applications. For this, we highlight the need to analyze the relationship among reaction kinetics, concentration effects, and reaction time scales, knowing that lack of such analysis could easily lead to failures. Further, possible issues such as chemical stability with various click reagents are also discussed to aid experimental designs. Recent examples and extensive references are also provided to aid in-depth understanding of technical details. We hope this review will help those interested in using click chemistry in drug delivery to select the appropriate reactions/reagents and minimize the number of pitfalls.

Objective:To investigate a 3D method of radiological evaluation of extra-articular scapular fracture and the treatment outcomes.Methods:A total of 19 patients with extra-articular scapular fracture were operatively treated and completely followed up at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from January 2014 to January 2020. They were 17 males and 2 females with an average age of 41 years (from 24 to 65 years). The medial-lateral displacement, antero-posterior angulation and glenopolar angle were measured on images of 3D reconstruction of the fractured scapulae by Mimics software. 3D reconstructions of the intact scapulae were made as controls in the patients with proximal humerus fracture matched in time and age (17 males and 2 females with an average age of 41 years). Operations were carried out via the modified Judet approach in the experimental group. The treatment outcomes in the experimental group were evaluated by the Constant-Murley absolute value scoring at 6 months after operation.Results:All the patients in the experimental group obtained a mean follow-up of 48 months (from 11 to 73 months). All fractures in the experimental group acquired anatomical reduction and fixation intraoperatively and bony union within 6 months after operation. In the experimental group, the medial-lateral displacement averaged 17.9 mm and the antero-posterior angulation 26.9° before operation while the anteflexion lifting angle 162.2°, the lateral external rotation 41.6°, and the Constant-Murley absolute value scores 93.2 points at 6 months after operation. Pre-operatively, the glenopolar angles were 34.4°±6.3° and 40.6°±6.6° for the experimental and control groups respectively, showing a significant difference between the 2 groups ( P<0.05). At 6 months after operation, the glenopolar angle was 38.4°±5.0° for the experimental group, showing a significant difference between pre- and post-operation ( P<0.05). Conclusions:3D reconstruction measurements with Mimics software help accurate characterization of extra-articular scapular fracture and evaluation of surgical indications. Open reduction and internal fixation of scapular fractures via the modified Judet approach may promise a satisfactory union rate and functional outcomes.

Objective:To analyze the treatment of scapular glenoid fractures via the modified Judet approach.Methods:A retrospective study was conducted of the 25 patients who had been treated for scapular glenoid fractures via the modified Judet approach and completely followed up at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital from January 2014 to January 2020. They were 19 males and 6 females with an average age of 46 years (from 29 to 66 years). According to the Goss-Ideberg classification, 8 cases were diagnosed as type Ⅱ, 2 cases as type Ⅳ, 10 cases as type Ⅴ and 5 cases as type Ⅵ. 3D reconstruction of the CT scans by software Mimics 16.0 was made to confirm the diagnoses and classifications of the fractures. Articular step-off and displacement of the scapular glenoid were calculated and recorded. The functional outcomes were evaluated by Constant-Murley scoring system at 6 months postoperatively.Results:Preoperatively, the mean articular step-off was 5.8 mm (from 1.2 to 6.3 mm) and the mean displacement 7.7 mm (from 2.1 to 12.9 mm). All fractures obtained bony union within postoperative 6 months. The mean follow-up period was 58.8 months (from 7 to 92 months). The forward flexion was 158.6° (from 125° to 180°) and the external rotation 39.0° (from 30° to 45°) at 6 months postoperatively. The mean Constant-Murley score was 92.6 (from 75 to 100) at 6 months post-operatively; 19 cases were excellent (76%), 5 were good (20%) and one was fair (4%), giving an excellent to good rate of 96% (24/25).Conclusion:For scapular glenoid fractures of Goss-Ideberg types Ⅱ/Ⅳ/Ⅴ/Ⅵ, surgery via the modified Judet approach may promise satisfactory reduction and fixation and fine clinical outcomes.

OBJECTIVE: To systematically evaluate therapeutic efficacy and safety of Compound muni ziqi granules in the adjuvant treatment of chloasma, and to provide evidence-based reference for clinical treatment. METHODS; Retrieved from Chinese Journal Full-text Database (CJFD), China Scientific Journal Database (CSJD), Wanfang database, Medline and Embase, randomized controlled trials (RCTs) about therapeutic efficacy (total response rate, cure rate, the decrease level of E2, FSH and LH in serum) and safety of Compound muni ziqi granules alone or combined with routine drug (trial group) vs. routine drug (control group) in the treatment of chloasma were collected. Meta-analysis was conducted by using Rev Man 5. 3 statistical software after data extraction of clinical studies meeting inclusion criteria and quality evaluation with Cochrane systematic evaluator manual 5. 1. 0. RESULTS: Totally 12 RCTs were enrolled, involving 1 100 patients. Results of Meta-analysis showed that total response rate [OR=2. 84, 95％CI(2. 20, 3. 67), P<0. 001], cure rate [OR=2. 11, 95％CI(1. 59, 2. 79),P<0. 001],decrease level of Ez [OR=-98. 64, 95％ CI (-110. 84, -86. 44), P <0. 001], decrease level of FSH [OR=-1. 85, 95％CI(-2. 58,-1. 11),P<0. 001] and decrease level of LH [OR= - 5. 85, 95％ CI (-6. 83, -4. 87), P<0. 001] in trial group were significantly better than control group, with statistical significance. In trial group, a few patients suffered from the increase of menstruation, the decrease of menstruation, temporary pigmentation and transient burnout; but all symptoms did not affect the treatment. CONCLUSIONS: Compound muni ziqi granules show definite clinical efficacy and good response rate in the adjuvant treatment of chloasma with mild ADR.

As a kind of intervention measures of traditional Chinese medicine, acupuncture-moxibustion is highly adopted on global clinical practice. Even though the global clinical trial registration system was established more than 10 years ago, the proportion of acupuncture-moxibustion clinical trial registration is still very low; and it is very problematic on the methodological quality and report quality in the published acupuncture-moxibustion clinical trials. In order to manage particularly the acupuncture-moxibustion clinical trials, China Academy of Chinese Medical Sciences, collaborated with China Association of Acupuncture and Moxibustion and World Federation of Acupuncture Societies, established the Acupuncture-Moxibustion Clinical Trail Registry (AMCTR). AMCTR is a secondary registry platform affiliated to the Chinese Clinical Trial Registry (ChiCTR) and WHO International Clinical Trials Registry Platform (ICTRP), specifically for the acceptance and management of clinical trials in the field of acupuncture and moxibustion. It is a nonprofit academic organization, located in China Academy of Chinese Medical Sciences.