Objective:To investigate the effects of visualized precision electrophysiological diagnosis and transcutaneous low-frequency electrical stimulation(TES)on hypoxia-induced ED in high-altitude areas.Methods:This study included 152 ED pa-tients from high-altitude hypoxic areas treated by TES based on the parameters obtained from visualized precision electrophysiological diagnosis.We followed up the patients for 1 to 3 months and compared their ⅡEF-5 scores,nocturnal penile tumescence and rigidity(NPTR)and infrared thermal metabolic technology(TMT)-based temperature of the whole body and diseased parts before and after treatment.Results:All the patients successfully completed 1 to 3 courses of TES.There were no statistically significant differences in the ⅡEF-5 scores(P＜0.05)and penile tip optimal erection rigidity and duration(P＜0.01)of the patients before and after treat-ment.TMT images indicated a temperature change of＞1.5 ℃ in the penis and bilateral inguinal regions after treatment,suggesting the effectiveness of electrical stimulation.No recurrence was observed during the follow-up.Conclusion:TES based on the parame-ters obtained from visualized precision electrophysiological diagnosis has a definite effect on hypoxia-induced ED by enhancing oxygen supply to the penile corpus cavernosum and improving its function and structure.

Objective:To explore the risk factors for duodenal papillary adenocarcinoma by comparing the differences in clinical and endoscopic features between patients with duodenal papillary adenomas and adenocarcinomas.Methods:This study retrospectively included patients diagnosed as having duodenal papillary adenocarcinoma and adenoma from January 1st 2018 to June 1st 2023 at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School. Demographic, clinical manifestations, laboratory tests, imaging, endoscopic and pathological characteristics of patients with adenomas and adenocarcinomas were collected and compared. Multivariable logistic regression analysis was employed to identify high-risk factors for duodenal papillary adenocarcinoma.Results:A total of 119 cases of adenocarcinoma and 171 cases of adenoma were included. There were statistically significant differences between the two groups in terms of patient age, body mass index (BMI), clinical symptoms, family history of malignant tumors, bile duct dilation, pancreatic duct dilation, lesion size, adenoma site classification, stage assessed by EUS, and involvement of the bile and pancreatic ducts ( P<0.05). Univariate logistic regression analysis revealed that non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, involvement of the bile and pancreatic ducts assessed by EUS, age ≥60 years, lesion size ≥1.5 cm, clinical symptoms, family history of malignant tumors, bile duct dilation, and pancreatic duct dilation were risk factors for duodenal papillary adenocarcinoma. Multivariate logistic regression analysis showed that non-ampullary lesions ( OR=7.00, 95% CI:1.44-34.15, P=0.016), involvement not limited to the major duodenal papilla assessed by EUS ( OR=13.77, 95% CI: 4.69-40.45, P<0.001), age ≥60 years ( OR=2.52, 95% CI: 1.23-5.18, P=0.011), bile duct dilation ( OR=2.58, 95% CI: 1.12-5.94, P=0.026), and lesion size ≥1.5 cm ( OR=2.76, 95% CI:1.36-5.59, P=0.005) were independent risk factors for duodenal papillary adenocarcinoma. Conclusion:This study shows the independent risk factors for duodenal papillary adenocarcinoma, which include non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, age ≥60 years, bile duct dilation, and lesion size ≥1.5 cm.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

OBJECTIVE To investigate the effects of brusatol on the malignant biological behavior of ovarian cancer cells by regulating the sphingosine kinase 1 （SPHK1）/sphingosine-1-phosphate （S1P）/sphingosine-1-phosphate receptor 3 （S1PR3） signaling pathway. METHODS Human ovarian cancer cell strain SKOV-3 were randomly divided into control group， brusatol group， SPHK1 overexpression group， brusatol+blank load group， brusatol+SPHK1 overexpression group. The cell viability， colony formation rate， the number of migration and invasion， apoptosis rate， the expressions of cell proliferation-related proteins [myelocytomatosis viral oncogene homolog （C-myc）]， apoptosis-related proteins [B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）]， epithelial mesenchymal transition （EMT）-related proteins （E-cadherin， N-cadherin） and SPHK1， S1P， S1PR3 proteins were all detected in each group. Transplanted tumor model of nude mice was constructed by using SKOV-3 cells and randomly separated into control group， brusatol low-dose， medium-dose and high-dose groups， SPHK1 overexpression group， high- dose brusatol+blank load group， and high-dose brusatol+SPHK1 overexpression group； the growth of transplanted tumors were detected. The nude mice model of SKOV-3 transplantation tumor was randomly divided into control group， brusatol group， SPHK1 overexpression group， brusatol+blank load group， and brusatol+SPHK1 overexpression group； the proliferation and apoptosis of transplanted tumor tissue， the expressions of EMT-related Δ 基金项目江西省中医药管理局科技计划项目（No.2023B0762） ＊第一作者 副主任药师 。研究方向 ：药学研究及药理学 。E- proteins and SPHK1/S1P/S1PR3 signaling pathway proteins mail：jsgj2023@126.com were detected in each group. RESULTS Cell experiments in # 通信作者 主任医师，硕士。研究方向：妇科及妇科肿瘤学。E- vitro had shown that compared with the control group， the cell mail：11638199@qq.com viability， clone formation rate， migration number， invasion 中国药房 2024年第35卷第16期 China Pharmacy 2024 Vol. 35 No. 16 · 1991 · number， protein expressions of C-myc， Bcl-2， N-cadherin， SPHK1， S1P and S1PR3 were decreased significantly in brusatol group （P＜0.05）， while the apoptosis rate， protein expressions of Bax and E-cadherin were increased significantly （P＜0.05）； overexpression of SPHK1 could weaken the effects of brusatol on the above indicators in SKOV-3 cells. Mice experiments in vivo had shown that compared with the control group， the transplanted tumor volumes of nude mice in the brusatol low-dose， medium- dose and high-dose groups were decreased significantly in a dose-dependent manner after 21 days of intervention （P＜0.05）. Brusatol of high dose could also significantly reduce the protein expressions of C-myc， Bcl-2， N-cadherin， SPHK1， S1P and S1PR3 in transplanted tumor tissue of nude mice （P＜0.05）， and significantly increase the protein expressions of Bax and E- cadherin （P＜0.05）； overexpression of SPHK1 could weaken the effects of brusatol on the above indicators in transplanted tumor tissue of nude mice. CONCLUSIONS Brusatol can inhibit the proliferation， cloning， EMT， migration and invasion of ovarian cancer cells， and induce their apoptosis by down-regulating the expression of SPHK1/S1P/S1PR3 signaling pathway. It can also inhibit the growth of ovarian cancer cells in nude mice， ultimately suppressing their malignant biological behavior and exerting significant anti-cancer effects on ovarian cancer.

Purpose: This study aimed to investigate whether nighttime elective surgery influenced the short-term outcomes and prognosis of hepatocellular carcinoma (HCC) patients. Methods: The 1,339 HCC patients who underwent hepatectomy were divided into the daytime surgery group (8 a.m.–6 p.m., n = 1,105) and the nighttime surgery group (after 6 p.m., n = 234) based on the start time of surgery. The 1:2 propensity score matching (PSM) analysis was used to control confounding factors. The short-term outcomes of HCC patients in the 2 groups were compared before and after PSM. Factors associated with major complications (Clavien-Dindo grade, ≥III) and textbook oncologic outcomes (TOO) were separately identified by multivariable logistic regression based on variables screened via least absolute shrinkage and selection operator (LASSO). The Kaplan-Meier method was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: TOO was achieved after surgery in 897 HCC patients. HCC patients in the nighttime surgery group had a higher body mass index (P = 0.010). After 1:2 PSM, the baseline characteristics of patients between the 2 groups were similar. Short-term outcomes in HCC patients were comparable both before and after PSM (all Ps > 0.05), as were TOO in the 2 groups before (P = 0.673) and after PSM (P = 0.333). In our LASSO-logistic regression, nighttime surgery was not an independent factor associated with major complications or TOO. Both groups also had similar OS (P = 0.950) and RFS (P = 0.740) after PSM. Conclusion Our study revealed the safety of nighttime elective hepatectomy for HCC patients.

Objective: To evaluate the efficacy of endoscopic transnasal surgery for sinonasal and skull base adenoid cystic carcinoma (ACC), and to analyze the prognostic factors. Methods: Data of 82 patients (43 females and 39 males, at a median age of 49 years old) with sinonasal and skull base ACC who were admitted to XuanWu Hospital, Capital Medical University between June 2007 and June 2021 were analyzed retrospectively. The patients were staged according to American Joint Committee on Cancer (AJCC) 8th edition. The disease overall survival(OS) and disease-free survival(DFS) rates were calculated by Kaplan-Meier analysis. Cox regression model was used for multivariate prognostic analysis. Results: There were 4 patients with stage Ⅱ, 14 patients with stage Ⅲ, and 64 patients with stage Ⅳ. The treatment strategies included purely endoscopic surgery (n=42), endoscopic surgery plus radiotherapy (n=32) and endoscopic surgery plus radiochemotherapy (n=8). Followed up for 8 to 177 months, the 5-year OS and DFS rates was 63.0% and 51.6%, respectively. The 10-year OS and DFS rates was 51.2% and 31.8%, respectively. The multivariate Cox regression analysis showed that late T stage and internal carotid artery (ICA) involvement were the independent prognostic factors for survival in sinonasal and skull base ACC (all P<0.05). The OS of patients who received surgery or surgery plus radiotherapy was significantly higher than that of patients who received surgery plus radiochemotherapy (all P<0.05). Conclusions: Endoscopic transonasal surgery or combing with radiotherapy is an effective procedure for the treatment of sinonasal and skull base ACC. Late T stage and ICA involvement indicate poor prognosis.
Male ; Female ; Humans ; Middle Aged ; Carcinoma, Adenoid Cystic/surgery* ; Retrospective Studies ; Skull Base/pathology* ; Disease-Free Survival ; Prognosis

The latest guideline about ulcerative colitis (UC) clinical practice stresses that mucosal healing, rather than anti-inflammation, is the main target in UC clinical management. Current mucosal dysfunction mainly closely relates to the endoscopic intestinal wall (mechanical barrier) injury with the imbalance between intestinal epithelial cells (IECs) regeneration and death, as well as tight junction (TJ) dysfunction. It is suggested that biological barrier (gut microbiota), chemical barrier (mucus protein layer, MUC) and immune barrier (immune cells) all take part in the imbalance, leading to mechanical barrier injury. Lots of experimental studies reported that acupuncture and moxibustion on UC recovery by adjusting the gut microbiota, MUC and immune cells on multiple targets and pathways, which contributes to the balance of IEC regeneration and death, as well as TJ structure recovery in animals. Moreover, the validity and superiority of acupuncture and moxibustion were also demonstrated in clinic. This study aims to review the achievements of acupuncture and moxibustion on mucosal healing and analyse the underlying mechanisms.
Rats ; Animals ; Colitis, Ulcerative/metabolism* ; Moxibustion ; Rats, Sprague-Dawley ; Acupuncture Therapy ; Acupuncture

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Fluorescence ; Arthritis, Rheumatoid/drug therapy* ; Interleukin-1 ; Arthritis, Experimental/drug therapy*

Objective To investigate the impacts of catalpol(CAT)on lead-induced neurotoxicity of PC 12 cells by regulating Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signal pathway.Methods PC 12 cells were randomly grouped into blank group(blank medium treatment),model group(25 μmol·L-1 lead acetate),experimental-L group(25 μmol·L-1 lead acetate+2.5 mg·L-1 CAT),experimental-H group(25 μmol·L-1 lead acetate+5.0 mg·L-1 CAT)and experimental-H+colivelin group(25μmol·L-1lead acetate+5.0 mg·L-1CAT+0.5 μmol·L-1 colivelin).Lactate dehydrogenase(LDH)assay was applied to detect cell damage;the apoptosis rate was detected by flow cytometry;the level of reactive oxygen species(ROS)was detected by fluorescence staining;the mRNA expression levels of JAK2 and STAT3 were measured by real-time quantitative polymerase chain reaction;Western blot was applied to detect the expression of JAK2/STAT3 signal pathway and apoptosis-related proteins in cells.Results The expression levels of B cell lymphomal/leukemia-2 protein in the blank group,model group,experimental-H group,experimental-H+colivelin group were 0.80±0.08,0.33±0.03,0.74±0.07 and 0.45±0.04;the cell LDH levels were(214.28±12.07),(376.50±28.46),(243.25±14.88)and(332.49±18.15)U·L-1;the ROS relative fluorescence intensity were 1.00±0.00,1.89±0.19,1.20±0.12 and 1.75±0.17;the cell apoptosis rates were(4.35±0.57)％,(26.59±1.96)％,(11.07±1.08)％and(21.63±2.06)％;the expression levels of JAK2 mRNA were 1.00±0.00,1.86±0.18,1.28±0.13 and 1.30±0.13;the expression levels of STAT3 mRNA were 1.00±0.00,1.94±0.19,1.34±0.13 and 1.72±0.17;the phosphorylation levels of p-JAK2/JAK2 were 0.26±0.03,0.78±0.08,0.38±0.04 and 0.36±0.07;the phosphorylation levels of p-STAT3/STAT3 were 0.23±0.02,0.84±0.08,0.42±0.04 and 0.75±0.07;the expression levels of Bax protein in cells were 0.31±0.03,0.86±0.08,0.40±0.04 and 0.69±0.07.The above indicators in the model group showed statistically significant differences compared to the blank group(all P＜0.05);the above indicators in the experimental-H group showed statistically significant differences compared to the model group(all P＜0.05).Conclusion CAT may reduce the lead-induced neurotoxicity of PC 12 cells by inhibiting the JAK2/STAT3 signal pathway.

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1β, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1β was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Chromatography, Liquid ; Interleukin-6 ; Tandem Mass Spectrometry ; Acupuncture Points ; Arthritis, Rheumatoid/drug therapy*