ObjectiveTo investigate the effect and mechanism of simvastatin pretreatment on kidney ischemia reperfusion injury （IRI） in mice. MethodsFifteen male C57BL/6 mice aged 6-8 weeks were divided into three groups： Sham operation group （Sham group）， kidney IRI group （IR group）， and simvastatin pretreatment+kidney IRI group （SIM group）. Hematoxylin-eosin （HE） staining of kidney tissue and detection of serum creatinine （SCr） and lactate dehydrogenase （LDH） were used to evaluate kidney injury. The levels of superoxide dismutase （SOD）， reduced glutathione （GSH）， malondialdehyde （MDA） and reactive oxygen species （ROS） were detected to evaluate oxidative stress. The contents of ferrous iron （Fe²⁺） and ferric iron （Fe³⁺） in kidney tissue were detected， and the morphological changes of mitochondria were observed by transmission electron microscope. The relative expression levels of Kruppel-like factor 2 （KLF2）， glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， and acyl-coa synthetase long chain family member 4 （ACSL4） protein in kidney tissue were detected. ResultsCompared with the IR group， the SIM group had significantly reduced renal tubular injury and decreased contents of Scr and LDH in serum （P < 0.001）. It also showed increased expression of SOD and GSH and decreased expression of MDA and ROS （P < 0.01）. Simvastatin pretreatment reduced the contents of Fe²⁺ and Fe³⁺ in the tissues （P < 0.01） and alleviated mitochondrial damage. It also promoted the expression of KLF2 （P < 0.01）， up-regulated the expression of ferroptosis-related protective proteins GPX4 and SLC7A11， and down-regulated the expression of ferroptosis-related damage protein ACSL4 （P < 0.05）. ConclusionSimvastatin pretreatment may inhibit kidney ferroptosis by promoting the expression of KLF2 to alleviate kidney IRI.

OBJECTIVE To provide references for the accurate identification and management of immune-related cutaneous adverse events （irCAEs） caused by durvalumab， and ensuring safe clinical drug use. METHODS Clinical pharmacists participated in the diagnosis and treatment process of a patient with gallbladder cancer who developed irCAEs caused by durvalumab. The clinical pharmacists systematically reviewed the patient’s past medical history and medication history， and assisted physicians in assessing the association between adverse drug reactions and administered drugs. Meanwhile， the clinical pharmacists conducted a graded assessment of the adverse reaction， proposed recommendations such as discontinuing durvalumab and adjusting the administration regimen of glucocorticoids， assisted physicians in restarting immunotherapy， and carried out medication education and other pharmaceutical care. RESULTS The occurrence of irCAEs in this patient was “highly likely” related to durvalumab and was classified as severe. The physicians adopted the clinical pharmacist’s opinion， and after symptomatic treatment， the patient’s skin symptoms improved， and discharged with medication. After the completion of glucocorticoid therapy for the patient， the physician restarted immunotherapy with tislelizumab， and no related adverse reactions occurred again in the patient. CONCLUSIONS Durvalumab can cause irCAEs such as severe skin maculopapular rash. In clinical practice， it is crucial to promptly identify and discontinue suspicious drugs， immediately implement effective symptomatic treatment measures， and actively resume immunotherapy to ensure the continuity and safety of the patient’s treatment.

[摘 要] 目的：探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌（TC）放射性碘抵抗的作用机制。方法：利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞（RR-TPC-1细胞）模型及裸鼠移植瘤模型，通过敲低或过表达DLEU2（si-DLEU2/OE-DLEU2）、抑制EZH2（UNC1999）、过表达IKKα（OE-IKKα）进行干预，采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果：TCGA分析显示，DLEU2在TC组织中显著上调（P < 0.001），与患者不良预后相关（P = 0.008 4），且与EZH2表达呈正相关（r = 0.390, P < 0.001）；RIP证实EZH2与DLEU2存在相互作用/结合（P < 0.05）。体外实验表明，敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平，抑制NF-κB通路活化（P < 0.05或P < 0.01），抑制细胞增殖、促进凋亡（均P < 0.05）。联合敲低DLEU2与抑制EZH2进一步增强上述效应，而过表达IKKα则可部分逆转上述效应（P < 0.05或P < 0.01）。体内实验进一步证实，敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长，增加肿瘤细胞凋亡（均P < 0.01）；IKKα过表达则部分逆转上述抗肿瘤效应（P < 0.05或P < 0.01）。结论：lncRNA DLEU2通过招募EZH2催化H3K27me3修饰，间接激活IKKα/NF-κB信号并形成正反馈环路，介导TPC-1细胞131I抵抗。

Objective To observe the value of transvaginal two-dimensional ultrasonography(2D-TVS)combined with three-dimensional ultrasonography OmniView for diagnosing intrauterine adhesion(IUA).Methods Totally 200 women with suspected IUA were retrospectively enrolled,including 172 cases who were ultimately diagnosed IUA and the rest 28 without IUA.The efficacy of 2D-TVS combined with OmniView for diagnosing IUA was analyzed.Results Among 200 cases,150 cases were diagnosed IUA with 2D-TVS(135 cases were diagnosed correctly),167 cases were diagnosed IUA with OmniView(159 cases were diagnosed correctly),and 170 cases were diagnosed with combination of the above two(165 cases were diagnosed correctly).The area under the curve(AUC)of 2D-TVS,OmniView and 2D-TVS combined with OmniView for diagnosing IUA was 0.625,0.819 and 0.890,respectively,and 2D-TVS combined with OmniView had the highest AUC(both P＜0.05),with sensitivity of 95.93％,specificity of 82.14％,positive predictive value of 97.06％and negative predictive value of 76.67％.Conclusion 2D-TVS combined with OmniView could be helpful for diagnosing IUA.

AIM:To investigate the modulatory effects of electroacupuncture(EA)on spinal cord neurons au-tophagy in rats with bone cancer pain.METHODS:(1)Verification of autophagy-related protein expression at different time points in a bone cancer pain model:a total of 56 female Sprague-Dawley(SD)rats were randomly divided into a sham-operated(sham)group and a model group.The model group was further subdivided into 6 subgroups corresponding to time points of 3,6,9,12,15,and 18 d,with 8 rats per subgroup.Thermal and mechanical pain thresholds,tibial bone destruction,and spinal neuron marker neuronal nuclear antigen(NeuN)co-localized with LC3B,Beclin1,and P62 were examined in rats at each designated time point.(2)Changes in spinal autophagy proteins following EA intervention:an additional 40 rats were randomly assigned to sham group,model group,EA group,sham EA(SEA)group,and autoph-agy agonist rapamycin(Rap)group,with 8 animals per group.EA was administered to the rats in EA group beginning on day 6 after modeling,the rats in SEA group received needle insertion without electrical stimulation,while those in Rap group received intraperitoneal injections of rapamycin(5 mg/kg).Thermal pain thresholds were assessed at designated in-tervals,followed by mechanical pain threshold assessments conducted on the subsequent day.Treatment continued until day 21,with rapamycin administered at the end of each intervention day.Tibial bone destruction was evaluated using he-matoxylin-eosin(HE)staining.Expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 proteins in the spinal cord were determined by Western blot and immunohistochemistry.RESULTS:(1)Compared with the Sham group,thermal and mechanical pain thresholds were significantly decreased in the model group starting from day 6(P<0.01).Rat tibial bones exhibited notable damage,with severity progressively increasing over time.Protein expression levels of LC3B Ⅱ/LC3B I,Beclin1,and P62 were significantly elevated in the spinal cord at various time points(P<0.01),and these pro-teins were co-localized with spinal cord neurons.(2)Compared with the model group,mechanical and thermal pain thresholds in the EA and Rap groups gradually increased,with statistically significant differences observed from days 8 and 6 onward,respectively(P<0.01).In addition,LC3B Ⅱ/LC3B I and Beclin1 protein expression levels were signifi-cantly upregulated(P<0.01),whereas P62 expression was markedly downregulated(P<0.01).Immunohistochemical analysis demonstrated significantly enhanced positive staining for LC3B Ⅱ/LC3B I and Beclin1 and significantly decreased positive staining for P62 in the spinal cord of rats in the EA and Rap groups(P<0.05).Notably,no significant differences were observed in the SEA group(P>0.05).CONCLUSION:EA promotes spinal cord neurons autophagy in rats with bone cancer pain.The enhancement of autophagy may represent a potential mechanism underlying the analgesic effect of EA in bone cancer pain.

Glycogen storage disease type Ⅱ,also known as Pompe disease,is an autosomal recessive metabolic myopathy with pulmonary hypertension as a rare complication.We reported a case of pulmonary hypertension in adult with late-onset glycogen storage disease type Ⅱ.Her arterial blood gas results indicated type Ⅱ respiratory failure,lung function indicated severe restricted ventilation dysfunction,sleep monitoring indicated severe sleep apnea hypopnea,severe nocturnal hypoxemia,echocardiography-derived systolic pulmonary pressure was 62 mmHg(1 mmHg=0.133 kPa),electromyography indicated myogenic lesion,and whole exon sequencing indicated GAA gene mutation.Supportive therapy and enzyme replacement therapy are applied in this patient.

Objectives:To observe the effectiveness and safety of recombinant human brain natriuretic peptide(rhBNP)for the treatment of patients with right heart failure caused by pulmonary arterial hypertension(PAH).Methods:A total of 421 patients with right heart failure caused by PAH who were hospitalized in Fuwai Hospital from January 2019 to June 2024 were retrospectively included in this study.All patients were treated with rhBNP on top of conventional therapy.24 h urine volume,body weight,liver and renal function index,electrolyte,uric acid,red blood cell distribution width(RBCDW),cardiac function,blood pressure and heart rate before and after the treatment of rhBNP were compared.Clinical symptoms,signs and the occurrence of adverse events during treatment were also observed.Results:Compared with baseline,after treatment with rhBNP,the 24 h urine volume increased.The levels of body weight,transaminase,total bilirubin,direct bilirubin,uric acid,RBCDW,systolic blood pressure,heart rate,and N-terminal pro-B-type natriuretic peptide significantly decreased(all P<0.05).There were no statistically significant differences in the levels of serum creatinine,and tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio(both P>0.05).Dyspnea and lower limbs edema were improved in 75.2%cases(227/302)and 66.9%cases(281/420)respectively.The incidence of adverse events and severe adverse events during rhBNP treatment were 1.2%(5/421)and 0.5%(2/421)respectively.Conclusions:Adding rhBNP on top of standard medication can effectively increase 24 h urine volume,reduce body weight,improve some prognostic indicators,improve the clinical symptoms and signs of heart failure without negatively affecting the renal function in right heart failure patients caused by PAH.Blood pressure should be closely monitored during the treatment process.

Objective To analyze the efficacy of vascularized lymph node transplantation(VLNT)combined with lymphatic venous anastomosis(LVA)in the treatment of secondary lower extremity lymphedema assisted by super microsurgical techniques.Methods A retrospective analysis was performed for 15 patients with secondary lower limb lymphedema who underwent VLNT+LVA surgery in the Department of Reconstructive and Reconstructive Microsurgery of Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2021 to July 2023,and compared the circumference and volume of each segment of the lower limb between the preoperative and postoperative 90 days.LVA according to the results of ICG examination,3-5 parts of the lower limb were selected for"Z"shaped surgery,and the lymphatic vessels and venules were anastomosed under the microscope in the subcutaneous fat layer.VLNT confirmed and labeled the saphenous branch of the descending knee artery and its accompanying veins in the popliteal fossa,and the latissimus dorsi lymph node flap was incised,and the flap vessels were anastomosed with the saphenous branch of the descending knee artery and its accompanying veins.Postoperative observation of flap vascularization.The circumference and volume of the affected limb were measured before surgery and 90 days after surgery.Results A total of 15 patients with lower extremity lymphedema were included without serious complications.Statistical analysis showed that the circumference of all levels of the affected limb and the volume of the affected limb were improved 90 days after operation compared with those before surgery.Among them,the limb circumference and volume at each level from the highest point of the dorsum of the foot to 52 cm above the ankle improved 90 days after the operation compared with those before the operation.Conclusion LNT+LVA treatment for secondary lower extremity lymphedema can effectively control edema and improve the function of the affected limb.

Objective Based on the concept of quality by design(QbD),to establish the design space of Zhihuang detumescence gel plaster extraction process.Methods With Zhihuang detumescence gel plaster as the model drug,geniposide content and extract yield as critical quality attributes(CQA),failure mode effects analysis(FMEA)combined with fishbone diagram was used to evaluate the risk of extraction process,and single factor experiment was used to determine the critical process parameters(CPPs).The mathematical model of CPPs and CQAs was established by Box-Behnken experimental design,and the design space was obtained and verified by Monte Carlo method.Results The ethanol volume fraction,solvent multiplication and extraction times were determined as CPPs,the mathematical model established by Box-Behnken experimental design was statistically significant at P＜0.05,and combined with the production experience,the resulting operable space was:ethanol volume fraction of 67％-70％,solvent multiplication of 7.5-9 times,and the number of times of extraction was 3 times,Extraction time 1 h.Conclusion The establishment of the extraction process design space of Zhihuang detumescence gel plaster is helpful to improve the quality stability and controllability of the traditional Chinese medicine compound preparation,lay an experimental foundation for the development of subsequent preparations,and provide a reference for the application of the design space method to the compound preparation of traditional Chinese medicine.

Objective To compare five time series models and predict the monthly incidence of bacillary dysentery in Qinghai Province in 2024,and provide reference for the prevention and control.Methods The epidemic charac-teristics of bacterial dysentery in Qinghai Province from 2014 to 2023 were analyzed.R4.3.1 software was used for establishing seasonal autoregressive integrated moving average(SARIMA)model,Holt-Winters triple exponential smoothing(Holt Winters)model,exponential smoothing(ETS)model,neural network autoregression(NNAR)model,and trigonometric seasonality,Box-Cox transformation,ARMA errors,trend and seasonal components(TBATS)model.Fitting effect of the models was analyzed and accuracy was compared.Results From 2014 to 2023,a total of 5 833 cases of bacterial dysentery were reported in Qinghai Province,without deaths,male to fe-male ratio being 1.23∶1.The highest incidence was reported in 2016(15.45 per 100 000 people),and the lowest in-cidence was reported in 2023(3.68 per 100 000 people).Incidence increased from 2014 to 2016,then decreased,showing an obvious overall downward trend.Case number in＜5 years age group was the highest,accounting for 29.76％of the total cases(n=1 736).Regarding population distribution,the top three were children in childcare institutions and scattered children(35.56％),farmers(24.65％),and students(12.62％).Except the additive Holt-Winters model,the predicted trends of the other four models were consistent with actuality.The ETS model had the best fitting effect,with a relatively balanced overall performance(training set:MAE=0.13,RMSE=0.21,MAPE=19.55％;testing set:MAE=0.11,RMSE=0.16,MAPE=28.66％).It is recommended to pre-dict the incidence of bacillary dysentery in Qinghai Province based on ETS model.Conclusion From 2014 to 2023,bacterial dysentery in Qinghai Province showed a downward trend,with the peak of the epidemic from June to Au-gust.Preschool and scattered children were high-risk groups.Among the five prediction models,ETS model has the best fitting effect,and can be used to predict the incidence of bacillary dysentery.