Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y₁₂ receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography-tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y₁₂ receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y₁₂ receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y₁₂ occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug-drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y₁₂ occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y₁₂ signaling pathway in cases of abnormal on-treatment platelet reactivity.

Perinatal depression is a psychological disorder that occurs during pregnancy and within one year of delivery, which can seriously affect the physical and mental health of pregnant and postpartum women, as well as the cognitive and behavioral abilities of offspring, with potential multigenerational effects. Therefore, it is important to identify its potential modifiable risk factors. Phthalic acid esters (PAEs), as common environmental endocrine disruptors, can affect maternal estrogen through multiple mechanisms and are important potential modifiable risk factors for developing maternal perinatal depression. At present, studies on the correlation between PAEs and perinatal depression are still very limited, and the mechanisms by which PAEs affect perinatal depression have not been clarified. Based on existing epidemiological and toxicological studies at home and abroad, the article briefly introduced the characteristics of multiple pathways, high doses, and long-term exposure to maternal PAEs, focused on reviewing the current status of epidemiological studies, pointed out the possible associations between some specific PAEs exposure and elevated risk of perinatal depression. It also summarized the potential roles of hormone-neurotransmitter pathway, inflammation mediation, gene regulation, and other possible mechanisms in the association between exposure to PAEs and perinatal depression. The article concluded with a look at how future research on the association between exposure to PAEs and perinatal depression can be scientifically validated, with a view to providing more high-quality evidence for the scientific prevention of the onset and progression of maternal depressive symptoms.

Objective To explore the effects of long non-coding RNA(lncRNA)small nucleolar molecule RNA host gene 12(SNHG12)targeting inhibition of miR-495-3p/phospholipinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling pathway on the proliferation,migration and invasion of prostate cancer cells.Methods The expressions of SNHG12 and miR-495-3p in prostate cancer tissues and cells(LNCaP,C4-2,DU145)were detected with real-time fluorescence quantitative PCR(qRT-PCR).After DU145 cells were divided into si-NC,si-SNHG12,si-SNHG12+anti-miR-NC and si-SNHG12+anti-miR-495-3p groups,the expressions of SNHG12 and miR-495-3p were detected with qRT-PCR;the targeting relationship between SNHG12 and miR-495-3p was determined with dual luciferase assay;cell proliferation was assessed with MTT assay;cell migration and invasion were evaluated with Transwell assay;the protein expressions of proliferating cell nuclear antigen(PCNA),N-cadherin,and E-cadherin were detected with Western blot.Results The expressions of SNHG12 were significantly increased,while the expression of miR-495-3P was significantly decreased in prostate cancer tissues and cells(LNCaP,C4-2,DU145)(P＜0.05).Knockdown of SNHG12 decreased DU145 cell activity,lowered the protein expressions of PCNA and N-cadherin,reduced the number of migrating and invading cells,but increased the protein expression of E-cadherin(P＜0.05).SNHG12 targeted and negatively regulated miR-495-3p,and down-regulation of miR-495-3p reversed the effects of SNHG12 knockdown on the proliferation,migration and invasion of prostate cancer cells.Compared with the si-NC group,the si-SNHG12 group had significantly decreased expressions of p-PI3K and p-Akt(P＜0.05).Compared with the si-SNHG12+anti-miR-NC group,the si-SNHG12+anti-miR-495-3p group had significantly increased protein expressions of p-PI3K and p-Akt(P＜0.05).Conclusion lncRNA SNHG12 can promote the proliferation,migration and invasion of prostate cancer cells through targeted inhibition of miR-495-3p/PI3K/Akt signaling pathway.

Objective To systematically retrieve,evaluate and integrate evidences about the assessment and management of perioperative pain in patients with acute aortic dissection.Methods PIPOST model was used to identify themes of assessment and management of perioperative pain.The literatures in the themes was systematically searched through the databases of UpToDate,JBI,BMJ Best Practice,practice guide REgistration for trans RAREncy(PREPARE),Guidelines International Network(GIN),National Guideline Clearinghouse(NGC),National Institute for Health and Care Excellence(NICE),Scottish Intercollegiate Guidelines Network(SIGN),New Zealand Guidelines Group(NZGG),Registered Nurses'Association of Ontario(RNAO),Australian Clinical Practice Guidelines(ACPG),American Heart Association(AHA),European Society of Cardiology(ESC),the Chinese Cochrane Center,Medlive,Cochrane library,PubMed,SinoMed,CNKI,Wangfan Data,and VIP.The retrieved literatures were evaluated and the evidences that met the inclusive criteria were extracted from the literatures by researchers who had trained for evidence-based study.Results A total of 17 studies,including 5 guidelines,3 expert consensus,6 systematic reviews and 3 randomised controlled trials were included in this study.Totally,29 pieces of best evidence were extracted in the assessment and management of pain in perioperative patients with acute aortic dissection,including pain assessment,basic principles of pain management,medication intervention strategies of pain management,non-medication intervention strategies of pain management,pain evaluation,education of pain management and organising pain management.Conclusion Evidences in assessment and management of pain in perioperative patients with acute aortic dissection can provide references and guidance for clinical practice.

Humans ; COVID-19 ; HIV Infections/drug therapy* ; Risk Factors

OBJECTIVE: To investigate the effectiveness of arthroscopic autologous iliac bone grafting with double-row elastic fixation in treatment of recurrent anterior shoulder dislocation combined with massive glenoid bone defects. METHODS: Between January 2018 and December 2021, 16 male patients with recurrent anterior shoulder dislocation combined with massive glenoid bone defects were treated with arthroscopic autogenous iliac bone grafting and double-row elastic fixation. The patients were 14-29 years old at the time of the first dislocation, with an average age of 18.4 years. The causes of the first dislocation included falling injury in 5 cases and sports injury in 11 cases. The shoulders dislocated 4-15 times, with an average of 8.3 times. The patients were 17-37 years old at the time of admission, with an average age of 25.1 years. There were 5 left shoulders and 11 right shoulders. The preoperative instability severity index (ISIS) score of the shoulder joint was 5.8±2.1, and the Beighton score was 4.3±2.6. The University of California Los Angeles (UCLA) score, Constant score, American Shoulder and Elbow Surgeons (ASES) score, and Rowe score were used to evaluate shoulder function, and the degree of the glenoid bone defect repair was observed based on CT after operation. RESULTS: All incisions healed by first intention, and no complication such as incision infection or neurovascular injury occurred. The patients were followed up 12 months. At 12 months after operation, UCLA score, Constant score, ASES score, and Rowe score all significantly improved when compared with the scores before operation ( P<0.05). CT imaging showed the degree of glenoid bone defect was significantly smaller at immediate, 6 and 12 months after operation when compared with that before operation ( P<0.05), and the bone blocks healed with the scapula, and bone fusion had occurred at 12 months. CONCLUSION Arthroscopic autologous iliac bone grafting with double-row elastic fixation is a safe treatment for recurrent anterior shoulder dislocation combined with massive glenoid bone defects, with good short-term effectiveness.
Humans ; Male ; Adolescent ; Adult ; Young Adult ; Shoulder Dislocation/surgery* ; Bone Transplantation/methods* ; Arthroscopy/methods* ; Joint Instability/surgery* ; Shoulder Joint/surgery* ; Scapula/surgery* ; Recurrence

Objective: To investigate the mechanism of resveratrol promoting fibronectin type Ⅲ domain-containing 5 (FNDC5) degradation in skeletal muscle of male obese mice． Methods: Six-week-old male C57BL /6 mice were randomly divided into three groups : standard control diet ( SCD) ，high-fat diet ( HFD) and high-fat diet treated with resveratrol (HFD + RES) ．HFD + RES group was intervened with resveratrol via gavage ［400 mg / kg · d) ］ while fed HFD for 20 weeks．The body mass，serum TG，TC，LDL-C and HDL-C levels were detected．The pathological changes in skeletal muscle were detected by HE staining．The expression of FNDC5，SIRT1，SIRT2，LC3， p62，Beclin-1，ATG5，ATG7 was assessed by immunohistochemistry，RT-PCR and Western blot respectively. Results: The body mass ，serum TG ，TC and LDL-C levels increased significantly ，meanwhile HDL-C levels decreased in HFD group．Lipid deposition between skeletal muscle fibers were obvious in HFD group．The immuno- histochemistry results showed that protein expression levels of SIRT1，SIRT2 and LC3 obviously decreased，while the protein levels of FNDC5 and p62 obviously increased．The expression levels of FNDC5 significantly increased， while the gene expression levels of SIRT1，SIRT2，LC3，Atg7 and Beclin-1 obviously decreased．All these responses were attenuated by treatment with RES． Conclusion RES has obvious effects of lipid-lowering and promoting FNDC5 degradation in skeletal muscle tissues，which may be related with SIRT1 and SIRT2-induced autophagy， thus resulting in degradation of FNDC5 .

ObjectiveTo investigate the clinical effect of laparoscopy, choledochoscopy, and duodenoscopy combined with T-tube-free drainage in the treatment of gallstones with common bile duct stones. MethodsA retrospective analysis was performed for the clinical data of 564 patients with gallstones and common bile duct stones who were admitted to Department of General Surgery, Pudong New Area People’s Hospital, Shanghai University of Medicine & Health Sciences, from December 2017 to December 2019. According to the surgical procedure, the patients were divided into laparoscopic transcystic common bile duct exploration (LTCBDE) group with 191 patients, three endoscopies+laparoscopic common bile duct exploration and primary suture (LBEPS) group with 138 patients, and endoscopic retrograde cholangiopancreatography (ERCP)+endoscopic sphincterotomy (EST)/endoscopic papillary balloon dilation (EPBD)+laparoscopic cholecystectomy (LC) group with 235 patients. The three groups were analyzed in terms of the general data including sex, age, bile duct diameter, and stone size/number, and surgical condition and complications were compared between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. ResultsThere were significant differences between the LBEPS group, the ERCP+EST/EPBD+LC group and the LTCBDE group in hospital costs, drainage volume, time to first flatus, length of hospital stay and time to extraction of drainage tube (F=416.40, 7.80, 33.99, 143.70, and 13.08, P＜0.001, P=0.020, P＜0.001, P＜0.001, and P＜0.001). Compared with the LBEPS group and ERCP+EST/EPBD+LC groups, the LTCBDE group had significantly lower hospital costs and a significantly longer time to first flatus, and significantly shorter length of hospital stay and time to extraction of drainage tube(all P＜0.05). No serious complication was observed after surgery, and there was no significant difference in the incidence rate of complications between the three groups (P＞0.05). All patients were discharged successfully after surgery. ConclusionThe three minimally invasive surgical procedures combined with T-tube-free drainage achieve the goal of little trauma and pain, fast postoperative recovery, and few serious complications, among which LTCBDE has the lowest treatment costs and the best postoperative recovery.

The globalized epidemic of the COVID-19 forced the international community to reconsider the importance and urgency of global public health in world peace and development. The authors analyzed the COVID-19 epidemic prevention and control situation in Africa, and discussed the functions and layout of China-Africa friendship hospitals from the perspective of global health governance. It was suggested that the functions of China-Africa friendship hospitals should be positioned as the high-level medical centers in Africa, regional medical and disease control linkage centers, regional health technology training centers, regional telemedicine collaboration center, and regional health policy research center.Furthermore, the layout of China-Africa friendship hospitals should respond to China′s assistance in the construction of Africa′s center for disease control and China-Africa′s cooperation plan for promoting the " one belt and one road" construction, and work together with the medical team to build a new pattern of medical integration and health care system for African disease prevention and control and medical treatment.