OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

Bone Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Objective:To analyze the difference and reliability of blood 17-hydroxyprogesterone (17-OHP), an indirect screening index for congenital adrenal hyperplasia (CAH), between preterm and full-term infants.Methods:In this retrospective cross-sectional study, a total of 210 285 newborns who underwent CAH screening at the Neonatal Screening Center of Shanghai Children′s Hospital from January 2019 to December 2022 were collected, including 14 312 premature infants and 195 973 full-term infants.The concentration of 17-OHP in dried blood spots on filter paper was determined by an automatic fluorescence analyzer.The distribution of 17-OHP levels in preterm and full-term infants and its statistical index were analyzed.The Kolmogorov-Smirnov test was used for normal distribution.The skewed distribution data was converted into approximately normal distribution using Box-Cox.Outliers were eliminated by the interquartile range method.The cumulative frequency distribution map was drawn by R language programming.The 99.5 th percentile value was used as the screening threshold and compared with the reference value given by the manufacturer or laboratory and with the reference change value (RCV). Results:According to the threshold provided by the laboratory, 26.76‰ of premature infants were tested positive in preliminary screening, and 4 were confirmed with an incidence of 1∶3 578, while 0.79‰ of full-term infants were tested positive in preliminary screening, and 11 were confirmed with an incidence of 1∶17 816.The thresholds for CAH screening established indirectly were 20.35 nmol/L in preterm infants and 10.78 nmol/L in full-term infants.The relative deviations between the indirect CAH screening thresholds and the manufacturer′s or laboratory′s CAH screening thresholds were higher than the RCV, respectively.According to the indirect CAH screening thresholds, the negative and positive coincidence rates of 65 samples in 13 batches from the Centers for Disease Control and Prevention interlaboratory quality assessment program in the United States reached 100%.A retrospective analysis of 210 285 neonates showed that 17-OHP concentration was higher than the screening threshold in all CAH-positive neonates.The application of this screening threshold reduced the false positive rate of preterm infants by 59.79%.Conclusions:It is feasible to establish the CAH screening thresholds for premature and full-term infants by an indirect method, which can improve the efficiency of screening and provide better diagnostic basis for clinical practice.

Radiation mainly comes from medical radiation,industrial radiation,nuclear waste and atmospheric ultraviolet radiation,etc.,radiation is divided into ionizing radiation and non-ionizing radiation.Studying the effects of ionizing and non-ionizing radiation on drug metabolism,understanding the absorption and distribution of drugs in the body after radiation and the speed of elimination under radiation conditions can provide reasonable guidance for clinical medication.This article reviews the effects of radiation on the pharmacokinetics of different drugs,elaborates the changes of different pharmacokinetics under radiation state,and discusses the reasons for the changes.

Objective:To analyze the clinical application value of a novel magnetic navigation ultrasound (MNU) combined with digital subtraction angiography (DSA) dual-guided percutaneous transhepatic biliary drainage (PTCD) through the right hepatic duct for the treatment of malignant obstructive jaundice.Methods:Randomized controlled trial. The clinical data of 64 patients with malignant obstructive jaundice requiring PTCD through the right hepatic duct at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province People′s Hospital) from December 2018 to December 2021 were retrospectively analyzed. The MNU group ( n=32) underwent puncture guided by a novel domestic MNU combined with DSA, and the control group ( n=32) underwent puncture guided by traditional DSA. The operation time, number of punctures, X-ray dose after biliary stenting as shown by DSA, patients' tolerance of the operation, success rate of the operation, pre- and post-operative total bilirubin, and incidence of postoperative complications were compared between the two groups. Results:The operation time of the MNU group was significantly shorter than that of the control group [(17.8±7.3) vs. (31.6±9.9) min, t=-6.35, P=0.001]; the number of punctures in the MNU group was significantly lower [(1.7±0.6) vs. (6.3±3.9) times, t=-6.59, P=0.001]; and the X-ray dose after biliary stenting as shown by DSA in the MNU group was lower than that in the control group [(132±88) vs. (746±187) mGy, t=-16.81, P<0.001]; Five patients in the control group were unable to tolerate the operation, and two stopped the operation, however all patients in the MNU group could tolerate the operation, and all completed the operation, with a success rate of 100% (32/32) in the MNU group compared to 93.8%(30/32) in the control group; the common complications of PTCD were biliary bleeding and infection, and the incidence of biliary bleeding (25.0%, 8/32) and infection (18.8%, 6/32) in the MNU group was significantly lower than that in the control group, 53.1% (17/32) and 28.1% (9/32), respectively. Conclusion:Magnetic navigation ultrasound combined with DSA dual-guided PTCD through the right biliary system for the treatment of malignant obstructive jaundice is safe and feasible.

【Objective】 To investigate the protective effects of aflexible sleeve penile protection device on reducing postoperative pain and wound edema in patients after circumcision. 【Methods】 A total of 54 patients who underwent circumcision at Yan’an Branch of Peking University Third Hospital during Feb.1 and May 31, 2023 were enrolled.The patients were randomly divided into the experimental group and control group, with 27 patients in either groups.Patients in the experimental group were treated with a flexible sleeve penis protection device after surgery, and patients in the control group were treated with traditional gauze bandage after surgery.Postoperative pain, wound edema and complications were compared between the two groups. 【Results】 In terms of pain, the visual analogue scale of the experimental group was significantly lower at 6 hours [(1.7±0.9) vs.(3.3±1.9), P<0.001] and 2 days [(2.0±1.3) vs.(3.3±1.3), P<0.001] after surgery than that of the control group, but there were no statistically significant differences between the two groups on the 4th and 7th postoperative days (P>0.05).In terms of edema, the edema score of the experimental group was significantly lower than that of the control group on the 2nd postoperative day [(2.0±1.0) vs.(4.0±0.8), P<0.001] , the 4th postoperative day [(1.5±1.2) vs.(2.6±0.9), P<0.001] , and the 7th postoperative day [(0.9±1.3) vs.(2.3±1.5), P<0.001] .There was no statistically significant difference in the incidence of complications between the two groups (P>0.05). 【Conclusion】 The flexible sleeve penile protection device has significant effects of reducing early postoperative pain and reducing edema in patients undergoing circumcision.

ObjectiveTo determine the syndrome of a rat model of follicular dysplasia induced by Tripterygium glycosides based on prescriptions and investigate the mechanism of traditional Chinese medicine intervention via the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/hypoxia-inducible factor-1 （HIF-1）/vascular endothelial growth factor （VEGF） pathway. MethodForty-eight rats with regular estrous cycles were randomly assigned into a normal group （n=8） and a modeling group （n=40）. The rats in the modeling group were administrated with Tripterygium glycoside suspension （75 mL·kg^-1） by gavage for 30 days. The modeled rats were assigned into model， Siwutang （3.69 g·kg^-1）， Youguiyin （3.11 g·kg^-1）， Zuoguiyin （7.29 g·kg^-1）， and Guishenwan （10.35 g·kg^-1） groups， with 8 rats in each group. The drug intervention lasted for 14 days. The changes of estrous cycle were detected by Pap staining， and a stereoscope was used to observe the morphology of the ovarian tissue. Hematoxylin-eosin staining was employed to observe the pathological changes and follicle count in the ovarian tissue. Enzyme-related immunosorbent assay （ELISA） was used to measure the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂） in the serum. Real-time fluorescence quantitative polymerase chain reaction and Western blot were employed to determine the mRNA and protein levels， respectively， of AMPK， mTOR， HIF-1， and VEGF in the ovarian tissue. ResultCompared with the normal group， the model group had a disordered estrous cycle， reduced secondary and mature follicles， increased atretic follicles， elevated FSH and LH levels， lowered E₂ level， up-regulated mRNA and protein levels of AMPK， and down-regulated mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with the model group， Guishenwan increased secondary and mature follicles， decreased atretic follicles， lowered the FSH and LH levels， elevated the E₂ level， down-regulated the mRNA and protein levels of AMPK， and up-regulated the mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with Guishenwan group， Siwutang， Youguiyin， and Zuoguiyin decreased mature follicles， increased atretic follicles （P<0.01）， elevated the LH （P<0.01） and FSH （P<0.05） levels， and lowered the E₂ level （P<0.05）. In addition， Youguiyin up-regulated the protein level of AMPK （P<0.05） and down-regulated the mRNA levels of mTOR and HIF-1 （P<0.01） as well as the mRNA and protein levels of VEGF （P<0.01）. Siwutang down-regulated the mRNA levels of mTOR and HIF-1 as well as the mRNA and protein levels of VEGF （P<0.05）. Zuoguiyin down-regulated the mRNA level of mTOR and the protein and mRNA levels of VEGF （P<0.05）. ConclusionGuishenwan may improve the ovarian function and promote follicle maturation in a rat model of follicular dysplasia by inhibiting the AMPK/mTOR/HIF-1/VEGF pathway， with the therapeutic effect superior to Zuoguiyin， Youguiyin， and Siwutang. It was hypothesized that this model presented the syndrome of kidney-essence deficiency.

Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway. Methods(i)A total of 72 specific pathogen-free(SPF)grade male Sprague Dawley(SD)rats were randomly divided into six groups,with 12 rats in each group:control,model,metformin(Met,0.18 g/kg)+fluoxetine(Flu,1.8 mg/kg),and the high-,medium-,and low-ZJJF dosages(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)groups.All groups except control group were injected once via the tail vein with streptozotocin(STZ,38 mg/kg)combined with 28 d of chronic unpredictable mild stress(CUMS)to establish diabetic rat models with de-pression.During the CUMS modeling period,treatments were administered via gavage,with control and model groups receiving an equivalent volume of distilled water for 28 d.The effi-cacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose,insulin,and glycated hemoglobin levels,along with behavioral assess-ments,including the open field test(OFT),forced swim test(FST),and sucrose preference test(SPT).Hippocampal tissue damage and neuronal apoptosis were evaluated using hema-toxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining.Apoptosis-related proteins Bax,Bcl-2,caspase-3,and the ex-pression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).(ii)To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological ef-fects of ZJJF,an additional 50 SPF grade male SD rats were randomly divided into five groups,with 10 rats in each group:control,model,SP600125(SP6,a JNK antagonist,10 mg/kg),ZJJF(20.52 g/kg),and ZJJF(20.52 g/kg)+Anisomycin(Aniso,a JNK agonist,15 mg/kg)groups.Ex-cept for control group,all groups were established as diabetic rat models with depression,and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period.Behavioral changes in rats were evaluated through the OFT,FST,and SPT,and hippocampal neuron damage and apoptosis were ob-served using HE staining,Nissl staining,TUNEL staining,and transmission electron mi-croscopy(TEM).Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed. Results(i)ZJJF significantly reduced the high blood glucose,insulin,and glycated he-moglobin levels in model rats(P<0.01).It increased autonomous activity and decreased de-spair-like behaviors(P<0.01),improved the pathological damage of hippocampal neurons,increased the number of neuronal nuclei(P<0.01),and reduced the number of mechanocytes,vacuolar cells,and apoptotic neurons(P<0.05,P<0.01,and P<0.01,respec-tively).ZJJF down-regulated the expression levels of pro-apoptotic proteins Bax and caspase-3(P<0.01),up-regulated the anti-apoptotic protein Bcl-2(P<0.01),and significantly inhibit-ed the overexpression of phosphorylated JNK(p-JNK),Elk-1,and c-fos(P<0.01).(ii)SP6 in-creased autonomous activity and reduced despair time in model rats(P<0.05),although it had no significant effects on sucrose preference(P>0.05).It increased the number of Nissl bodies in hippocampal neurons(P<0.01),reduced the protein expression levels of Bax(P<0.01)and caspase-3(P<0.05),and decreased the number of apoptotic neurons(P<0.05).SP6 also increased the expression level of Bcl-2(P<0.01),and inhibited the high expression levels of p-JNK,Elk-1,and c-fos(P<0.01,P<0.01,and P<0.05,respectively),suggesting that hip-pocampal neuronal apoptosis in diabetic rats with depression is associated with abnormal ac-tivation of JNK signaling pathway.Compared with ZJJF group,ZJJF+Aniso group showed a decrease in sucrose preference(P<0.05)and an increase in despair time(P<0.01)with more notable hippocampal neuronal damage.This group also exhibited a decrease in expression level(P<0.01)Bcl-2 and an increase in expression levels of Bax,caspase-3,p-JNK,Elk-1,and c-fos(P<0.01,P<0.05,P<0.05,P<0.01,and P<0.05,respectively),indicating that the antidepressant effects of ZJJF,its improvement of neuronal apoptosis,and regulation of JNK signaling molecules could all be reversed by a specific JNK agonist. Conclusion ZJJF exerts a significant hypoglycemic effect and ameliorates the apoptosis of hippocampal neurons by inhibiting the activation of JNK signaling pathway,which is a promising formula for the treatment of diabetic depression in clinical settings.