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 clinical characteristics,distribution of traditional Chinese medicine(TCM)syndrome types,and the anxiety and depression status in patients with colorectal polyps.Methods From January 2022 to December 2023,a total of 200 cases of patients with colorectal polyps(polyp group)and 100 patients without intestinal abnormalities(non-polyp group)under colonoscope who received colonoscopy or treatment at the Endoscopy Center of Dongguan Hospital,Guangzhou University of Chinese Medicine were enrolled.The relevant medical information of the patients in the two groups were collected,and then TCM syndrome differentiation of patients with colorectal polyps were carried out,the general infromation including gender,age,body mass index(BMI),smoking history and alcohol-intake history was recorded,and Hospital Anxiety and Depression Scale(HAD)score was calculated for assessing their anxiety and depression status.Results(1)The investigation of clinical characteristics showed that between the polyp group and the non-polyp group,the differences in the general information of gender,age,BMI,smoking history and alcohol-intake history were statistically significant(P<0.05 or P<0.01).As for the gender,the polyp group was predominated by the male(63.5%),while the non-polyp group was predominated by the female(58.0%),indicating that male patients were more likely to suffer from colorectal polyps.In terms of the age,the age group of 51-60 years old accounted for a higher percentage(36.0%)in the polyp group,while the age group of 41-50 years old accounted for a higher percentage(38.0%)in the non-polyp group,indicating that the polyp group had an elder average age than the non-polyp group.In addition,the percentages of patients with obesity(BMI≥28.0 kg/m2),smoking history,and alcohol-intake history in the polyp group were higher than those in the non-polyp group.(2)The analysis of features of colorectal polyps showed that the polyps were mostly seen in the left colon,accounting for 53.5%in the polyp group;adenomatous polyps accounted for 57.0%of all polyps;the size of colorectal polyps was usually less than one centimeter,accounting for 81.5%of all polyps;single colorectal polyps accounted for 45.5%,and multiple colorectal polyps accounted for 54.5%,indicating that colorectal polyps were usually multiple.(3)Among the 200 patients with colorectal polyps,there were 93 cases of syndrome of stagnation dampness due to spleen deficiency(46.5%),59 cases of dampness-heat in large intestine syndrome(29.5%),27 cases of liver depression and qi stagnation syndrome(13.5%),and 21 cases of dampness and blood stasis obstruction syndrome(10.5%).There were no statistically significant differences in the distribution of TCM syndrome types among colorectal polyp patients with different genders,ages,BMIs and alcohol consumption(P>0.05).The difference in the distribution of TCM syndrome types among colorectal polyp patients with or without smoking history was statistically significant(P<0.05).No statistically significant differences were shown in the distribution of TCM syndrome types among the colorectal polyp patients with various foci,number of polyps,and pathological types(P>0.05).The difference in the distribution of TCM syndrome types in colorectal polyp patients with different polyp sizes was statistically significant(P<0.05).In the patients with the polyp size0.05).In addition,the differences of anxiety scores and depression scores in the patients with various TCM syndrome types were not statistically significant(P>0.05).Conclusion(1)The distribution of TCM syndrome types of colorectal polyps is predominated by the syndrome of stagnation dampness due to spleen deficiency and dampness-heat in large intestine syndrome.The distribution of TCM syndrome types has no correlation with anxiety and depression,and the polyp foci,number of polyps,and pathological types of polyps,but has certain correlation with the size of the polyps.(2)Anxiety and depression may be the risk factors for colorectal polyps,but the polyp foci,number of polyps,and pathological types of polyps have no correlation with anxiety and depression,and the size of polyps may have certain correlation with anxiety.(3)Gender,age,smoking history and alcohol-intake history may be the risk factors for colorectal polyps.

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．

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.

BACKGROUND:Studies have shown that the vulnerability and elasticity of carotid plaques are related to the presence and degree of neovascularization within the plaque. Ultrasound,as the preferred measure to screen and evaluate vulnerable carotid plaques,is non-invasive,easy to perform,highly reproducible and radiation-free.OBJECTIVE:To investigate the influencing factors of vulnerable carotid plaque in the high-risk stroke population based on clinical baseline characteristics and carotid ultrasound parameters,and to develop a Nomogram prediction model based on independent risk factors.METHODS:A total of 180 patients who were identified to be at high risk of stroke by stroke screening at Fuzhou First People's Hospital from November 2021 to November 2023 were retrospectively selected as the study objects,and the patients were divided into a modeling set (n=126) and a validation set (n=54)at a ratio of 7∶3. According to the results of carotid artery ultrasound,the subjects in the modeling set were divided into a vulnerable plaque group (n=54) and a non-vulnerable plaque group (n=72). Independent risk factors were obtained by multi-factor Logistic regression,and a Nomogram model was constructed. Decision curves were drawn using R language to evaluate the clinical benefit of the model. The predictive efficacy of the model was tested by receiver operating characteristic curve and calibration curve,and the case data of the validation set were analyzed for external validation.RESULTS AND CONCLUSION:Multivariate Logistic regression results showed that age,family history of stroke,maximum carotid plaque thickness,carotid plaque quantity,urine microalbumin,urine microalbumin/creatinine ratio were associated with vulnerable carotid plaques in patients at high risk of stroke (P<0.05). The area under curve of the established Nomogram model was 0.917,and the sensitivity and specificity were 79.6％ and 91.7％,respectively. The results of decision curve showed that the potential clinical benefit of this model was considerable and its usability was high. The calibration curve results showed that the model had good prediction accuracy. The verification set results showed that the external prediction performance of the model was good. To conclude,age,family history of stroke,and maximum carotid plaque thickness in the high-risk population are all factors that influence this prediction model. This Nomogram based on these independent risk factors can provide a powerful reference for the clinical treatment of this high-risk population.

Objectives:To investigate the predictive value of Murray's law-based quantitative flow ratio(μQFR)in side branches for long-term clinical prognosis in patients with non-left main bifurcation lesions who underwent simple main branch stenting,and to provide a potential functional assessment standard for intervention decision-making on coronary bifurcation lesions.Methods:A retrospective analysis was conducted in 408 patients with non-left main bifurcation lesions who underwent simple main branch stenting at Lianyungang First People's Hospital and Nanjing First Hospital between July 2018 and January 2021.The study utilized third-generation QFR software to analyze pre-and post-procedure anatomical and functional parameters of the target lesion's main branch and key branches.The primary endpoint was target vessel failure(TVF)events during the 3-year follow-up.Patients were stratified into TVF and non-TVF groups.Baseline characteristics,procedural data,and pre-/post-procedural parameters of target vessels were compared between groups.Multivariable Cox regression was performed to identify predictors of TVF.Diagnostic efficacy of predictors was evaluated using area under the receiver operating characteristic(ROC)curve(AUC)with DeLong's method for comparison.Patients were dichotomized based on the optimal cutoffof post-procedural side branch μQFR,with TVF incidence rates compared via Cox regression and Kaplan-Meier analysis.Results:During 3-year follow-up,54 patients(13.2%)experienced TVF(TVF group),data were compared with 354 patients(86.76%)without TVF(non-TVF group).The TVF group showed higher post-procedural side branch diameter stenosis([32.93±17.80]%vs.[22.62±11.96]%,P<0.001)and lower μQFR(0.80±0.10 vs.0.89±0.07,P<0.001).Multivariate Cox regression identified higher post-procedural side branch μQFR as an independent protective factor against 3-year TVF(per 0.01 increase:HR=0.903,95%CI:0.850-0.959,P<0.001).ROC curves indicated that post-procedural side branch μQFR had moderate diagnostic efficacy for predicting 3-year TVF(AUC=0.769,95%CI:0.678-0.861,P<0.001),with a significantly higher AUC value than post-operative side branch area stenosis and minimal lumen diameter(both P<0.001),the optimal cutoffvalue was 0.84.Multivariate Cox regression and Kaplan-Meier survival analysis revealed markedly higher 3-year TVF rates in patients with μQFR≤0.84 compared to patients with μQFR>0.84(HR=4.007,95%CI:2.342-6.855,P<0.001;28.3%vs.7.9%,log-rank P<0.001).Conclusions:For patients with bifurcation lesions not involving the left main,the immediate post-procedural side branch μQFR could better predict 3-year TVF than anatomical indices.Maintaining post-stenting side branch μQFR>0.84 may optimize clinical outcomes when using a single-stent strategy.

Objective To investigate the neuroprotective effect of ligustilide(LIG)-mediated phosphatase and tensin homolog(PTEN)-induced putative kinase 1(PINK1)/Parkin pathway on mitophagy in rats with cerebral ischemia-reperfusion injury.Methods 161 male Sprague Dawley(SD)rats were randomly divided into sham operation(Sham)group,model group,LIG low-dose group,LIG high-dose group,mitophagy inhibitor(Mdivi-1)group,LIG high-dose+Mdivi-1 group,and the positive drug Nimodipine(NMDP)group,each with 23 rats.A modified middle cerebral artery wire thrombus method was used to construct a cerebral ischemia/reperfusion model in rats,and the neurobehavioral scores of rats in each group were compared by Longa's five-point scale;the volume of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TCC)staining,the histopathology and ultrastructure of the hippocampus were examined by hematoxylin-eosin(HE)staining and transmission electron microscope(TEM).And the Na+-K+-Adenosine Triphosphate was measured by enzyme-linked immunosorbent assay(ELISA);double immunofluorescence staining for translocase of the outer membrane of mitochondrion 20(TOMM20)and Microtubule-associated protein 1 light chain 3(LC3)co-localized area percentage.Flow cytometry assay(FCM)to test the level of reactive oxygen(ROS);real-time fluorescence quantitative PCR(qRT-PCR)was used to measure the relative content of mitochondria in hippocampal neurons;and Western blot was performed to test the level of autophagy and the PINK1/Parkin pathway related protein expression.Results Compared with the Sham group,the neurological function score and cerebral infarction volume of the model group were increased,the hippocampal neurons showed pathological damage such as disordered arrangement,nucleolus disappearance and partial shrinkage of the nucleus and plasma,nuclear membrane rupture,swelling,membrane rupture and crista reduction of some mitochondria,a large number of autophagosomes were observed,and the colocalization area percentage of TOMM20 and LC3 was increased.TOMM20 and cytochrome C oxidase subunit IV isoform 1(COX4I1)in hippocampus and selective autophagy adaptor protein 62(p62)protein expression,mitochondrial encoded ATP synthase 6(mt-ATP6)/Ribosomal protein L13(Rpl13)ratio and Na+-K+-ATPase content decreased,while PINK1 and Parkin protein expression,LC3-II/I ratio and ROS relative content increased,and the differences were statistically significant(t=4.602～52.012,all P<0.01).Compared with the model group,the neurological function score,cerebral infarction volume,pathological and ultrastructural damage of hippocampal neurons were significantly improved in the LIG low,high dose and NMDP groups,and the differences were statistically significant(t=4.851～12.525,all P<0.01).The colocalization of TOMM20 and LC3 and the content of Na+-K+-ATPase were increased,while the expression of TOMM20,COX4I1 and p62 proteins and the mt-ATP6/Rpl13 ratio were decreased in the high-dose LIG group.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were increased,and the differences were statistically significant(t=4.087～33.211,all P<0.01).Compared with the LIG high-dose group,the Mdivi-1 and LIG+Mdivi-1 groups had significantly decreased colocalization of TOMM20 and LC3 and Na+-K+-ATPase content,and significantly increased expression of TOMM20,COX4I1 and p62 proteins and mt-ATP6/Rpl13 ratio.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were decreased,and the differences were statistically significant(t=4.008～43.415,all P<0.01).However,the percentage of TOMM20 and LC3 co-localization area,PINK1 and Parkin protein expression,LC3-II/I ratio and Na+-K+-ATPase content in the hippocampus of the LIG+Mdivi-1 group were higher than those of the Mdivi-1 group.The protein expression of COX4I1 and p62,mt-ATP6/Rpl13 ratio and ROS level were lower than those in MDIV-1 group,and the differences were statistically significant(t=3.721～21.513,all P<0.01).Conclusion LIG may activate mitophagy by regulating PINK1/Parkin signaling pathway to protect neurons from cerebral ischemia-reperfusion injury in rats.