ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

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.

With the popularization of 5G communication technology and the continuous upgrade of robot-assisted surgery system,telesurgery has developed rapidly.However,there are few of reports about this technique in single-port laparoscopic gynecological surgery.On April 19,2024,the surgeons at the Second Affiliated Hospital of Naval Medical University in Shanghai successfully implemented robot-assisted single-port laparoscopic bilateral adnexectomy for a patient who was admitted to the Naval Hospital of the Eastern Theater Command in Zhoushan,Zhejiang Province through 5G communication technology.The operation time was 90 min,intraoperative bleeding was 20 ml,and no intraoperative complications occurred.There were no adverse events caused by robots such as robot system failure and instrument failure,or adverse events caused by remote communication such as network interruption and network attack.Intraoperative user datagram protocol(UDP)real-time monitoring data showed an average delay of 108 ms(range,105-111 ms)and a packet loss rate of 0.04%.The surgeons had a slight sense of delay when the operation amplitude was too large.There was no obvious stalling which affected the process of the operation.The patient was able to move around on the first day after surgery,and the catheter was removed.No postoperative complications occurred.The patient was discharged from the hospital on the second day after surgery.Postoperative pathological results revealed left fallopian tube ovarian serous cystadenofibroma,fallopian tubal tissue;right fallopian tube ovarian,sent for examination as ovarian and fallopian tube tissue.There were no complaints of discomfort during reexamination one month after surgery,and the umbilical incision healed well.This case is an attempt of telesurgery in the field of gynecology,and provides experiences for the further development of this technique.

Objective:To investigate the effects of toosendanin(TSN)on the proliferation,apoptosis,migration and invasion of esophageal squamous cell carcinoma(ESCC)KYSE150 cells,and to elucidate its underlying molecular mechanisms.Methods:CCK-8 assay,colony formation assay,and EdU assay were used to assess the effects of varying TSN concentrations(0.062 5,0.125,and 0.25 μmol/L)on KYSE150 cell proliferation.The impacts of TSN on the apoptosis,migration,and invasion of KYSE150 cells were evaluated using flow cytometry,wound healing assay,and Transwell chamber assay,respectively.The expression of hypoxia-inducible factor 1 alpha(HIF1A)in esophageal cancer tissues was analyzed using the GEPIA database.qPCR was used to detect the expression level of HIF1A mRNA in human esophageal epithelial Het-1A and KYSE150 cells,and in TSN-treated KYSE150 cells.Western blot(WB)was performed to detect the effects of TSN on the upstream signaling pathway AKT/mTOR of HIF1A and the expression of downstream proteins related to cell migration,invasion,and apoptosis.Results:TSN of varying concentrations significantly inhibited proliferation,migration,and invasion of KYSE150 cells and promoted apoptosis in a dose-dependent manner(P<0.05 or P<0.01).HIF1A mRNA was highly expressed in KYSE150 cells,and its expression was significantly downregulated after TSN treatment(P<0.05 or P<0.01).TSN markedly downregulated the expression of HIF1A and key upstream signaling proteins p-AKT and p-mTOR.In addition,TSN significantly suppressed the expression of downstream proteins associated with cell migration,invasion,and apoptosis,including N-cadherin,vimentin,Bcl-2,and caspase-3,while upregulating the expression of E-cadherin(P<0.05 or P<0.01).Conclusion:TSN inhibits the proliferation,migration,and invasion,and induces apoptosis in ESCC KYSE150 cells by down-regulating HIF1A expression through suppression of the AKT/mTOR signaling pathway.

Aim To investigate the predictive value of the Murray law-based quantitative flow ratio(μQFR)after target vessel pretreatment for vascular-related adverse events in patients with de novo coronary lesions treated with drug-coated balloon.Methods This retrospective study included 223 lesions from 223 patients who underwent drug-coated balloon-only strategy and completed 2-year clinical follow-up.Coronary angiographic images of target vessels pre-procedure,post-balloon and post-procedure were collected,and analyzed using a novel Murray's law-based algorithm.The μQFR analysis of each target vessel included not only the μQFR value of the target vessel,but also the length of the target vessel,the degree of vessel diameter stenosis,the reference lumen diameter,the minimum lumen diameter and blood flow velocity.The primary endpoint was defined as the postoperative vessel-oriented composite endpoint(VOCE).Results During the2-year clinical follow-up period,a total of 25 patients(11.2%)experienced VOCE events.Com-pared with the control group,patients with VOCE events after pretreatment showed a decrease in μQFR(P<0.001).Multivariate Logistic analysis showed that a lower target vessel μQFR after pretreatment(OR=0.931,95%CI:0.894～0.969,P<0.001)was an independent predictor of VOCE events.ROC curve analysis showed that the cut-off value for predicting 2-year VOCE events using preprocessed μQFR was 0.83(95%CI:0.727～0.840),with a sensitivity of 72.7%and a specificity of 84.0%(AUC=0.773,95%CI:0.676～0.870,P<0.001).Survival analysis showed that compared with patients with μQFR>0.83,patients with μQFR≤0.83 had a significantly higher incidence of VOCE events at 1 and 2 years,increasing to 3.909 times(16.9%vs.4.6%,HR=3.909,95%CI:1.539～9.930,P=0.004)and 2.867 times(19.7%vs.7.2%,HR=2.867,95%CI:1.301～6.316,P=0.009).After adjusting for potential con-founds,patients with pretreated μQFR≤0.83 had a 2.567 times in 2-year incidence of VOCE events(HR=2.567,95%CI:1.151～5.727,P=0.021)and a 3.712 times in 1-year incidence of VOCE events(HR=3.712,95%CI:1.478～9.810,P=0.006)compared to patients with good pretreatment.Conclusions For patients with in situ coronary artery disease,a lower μQFR after pretreatment increases the risk of postoperative adverse clinical events.μQFR≤0.83 may be used to evaluate the effectiveness of lesion pretreatment.

Objective To investigate the safety of robotic single-site hysterectomy(RSSH)for benign diseases.Methods We retrospectively analyzed data of patients who underwent RSSH or traditional transumbilical laparoendoscopic single-site hysterectomy(LESSH)for benign indications from May 2024 to May 2025.The study was comprised of 24 patients in the RSSH group and 42 patients in the LESSH group.Perioperative indicators were compared between the two groups.Results All the surgeries were successfully completed in both groups without conversion or intraoperative/postoperative blood transfusion.The RSSH group had a longer operation time than the LESSH group[161.5(131.3,179.5)min vs.97.5(76.5,123.3)min,Z=-5.226,P＜0.001].However,there were no significant differences in intraoperative blood loss,pre-postoperative hemoglobin difference,postoperative pain score,maximum postoperative temperature,time to flatus,indwelling catheter duration,or postoperative hospital stay(P＞0.05).Conclusion RSSH for benign diseases has a safety profile comparable to traditional LESSH.

Polycythemia vera(PV)is a type of BCR∷ABL1 negative myeloproliferative neoplasms(MPN),which is a chronic myeloid tumor caused by gene mutations in hematopoietic stem cells.PV has a certain risk of progressing to myelofibrosis or acute myeloid leukemia.At present,the goal of PV treatment is still to prevent thrombosis.With the deepening of PV research,it is possible to trans-form the lifelong treatment to prevent the progres-sion of the disease from alleviating the symptoms of patients.This article reviews the mechanism of traditional cytoreductive therapy drugs and the lat-est clinical trial results,as well as the early clinical trial data and their mechanism of action of new PV drugs and combination of drugs,in order to pro-vide help for researchers who pay attention to PV treatment.

Objective : To investigate the effect of environmental enrichment on cognitive impairment and hippo- campus GAP-43 changes induced by exposure to obstructive sleep apnea-hypopnea syndrome ( OSAHS) during the period of late pregnancy in mice，and to explore relative inflammatory pathway mechanism． Methods : The experi- mental group of C57BL/6J pregnant mice were exposed to an intermittent hypoxic environment for 7 consecutive days starting from gestational day 15．The corresponding offspring were then placed in an enriched environment from postnatal day 21 to 2 months of age (designated as OSAHS + EE group) or in a normal environment (designat- ed as OSAHS group) ．Pregnant mice in the control group were maintained in a normal oxygen environment，and their corresponding offspring were placed in an enriched environment (designated as Control + EE group) or a nor- mal environment (designated as Control group) at the same ages．The spatial learning and memory ability of the mice was assessed by Morris water maze at the age of 2 months．The mRNA levels of NF-kB，NLRP3 and GAP-43 in the hippocampus were detected by real-time fluorescence quantitative PCR , and the protein levels of NLRP3 and GAP-43 in the hippocampus were detected by Western blot． Results: Compared with Control group，the swimming distance increased (P＜0. 01) ，and the percentage of swimming distance in target quadrant decreased (P＜0. 01) in OSAHS group．The level of NF - κB mRNA，NLRP3 mRNA and protein in the hippocampus was increased，and the level of GAP-43 mRNA and protein was decreased (P＜0. 01) ．Compared with the Control group，there were no significant differences in swimming distance，percentage of swimming distance，NF-κB mRNA，NLRP3 mRNA and protein content in the OSAHS + EE group． Conclusion OSAHS during pregnancy impairs the learning and memory ability of offspring mice and reduces the level of GAP-43 protein．The mechanism may be related to the in- crease of NF-κB / NLRP3 level，and environmental enrichment can improve the damage．

Objective To evaluate postoperative recovery and health-related quality of life in patients undergoing robotic,laparoscopic,or open total hysterectomy.Methods A total of 152 patients who underwent total hysterectomy at the Department of Obstetrics and Gynecology of The Second Affiliated Hospital of Naval Medical University from May 2022 to May 2024 were enrolled and assigned to robot-assisted laparoscopic surgery group(robotic surgery group,44 cases),traditional laparoscopic surgery group(laparoscopic surgery group,62 cases),or open surgery group(46 cases)based on the surgical approach.General information,perioperative indexes,and discomfort symptoms 1 month after discharge were collected.Health-related quality of life was evaluated using 36-item short-form health survey(SF-36)at 1-month postoperative follow-up.Results There were no significant differences in age,body mass index,education level,work status,or diagnosis of benign or malignant diseases(all P＞0.05).The postoperative hospital stay,time of first ambulation,time of first oral intake,and 24-h pain score in the robotic surgery group were significantly lower than those in the laparoscopic and open surgery groups(all P＜0.01).The incidence of urinary system and digestive system discomfort within 1 month after discharge was significantly lower in the robotic surgery group than in the laparoscopic and open surgery groups,and the incidence of lower abdominal pain was significantly lower in the robotic surgery group than in the open surgery group(all P＜0.01).The scores of SF-36 in each dimension were significantly higher in the robotic surgery group than those in the laparoscopic and open surgery groups 1 month after discharge(all P＜0.01).Conclusion Compared with those undergoing traditional laparoscopic or open total hysterectomy,patients who underwent robot-assisted laparoscopic total hysterectomy demonstrate faster postoperative recovery and better health-related quality of life.