ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell （hUC-MSC） with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis （CLF）. MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC （hUC-MSC^Numb-OE）， and hUC-MSC transfected with empty vector （hUC-MSC^OE-EV） was used as negative control. Bile duct ligation （BDL） was performed to establish a rat model of CLF， and then the rats were randomly divided into BDL group， hUC-MSC group， hUC-MSC^OE-EV group， and hUC-MSC^Numb-OE group， while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL， and samples were collected at the end of week 4. Related indicators were measured， including serum biochemistry， liver histopathology， the content of hydroxyproline （Hyp） in the liver， hepatic stellate cell activation， ductular reaction， liver regeneration， and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group， the hUC-MSC group and the hUC-MSC^OE-EV group had significant reductions in the levels of serum biochemical parameters （aspartate aminotransferase， gamma-glutamyl transpeptidase， total bile acid， total bilirubin， and direct bilirubin）， liver fibrosis markers （the content of Hyp and the expression levels of alpha-smooth muscle actin， tumor necrosis factor-α， and transforming growth factor-beta 1）， and ductular reaction markers （the expression levels of CK7 and CK19） （all P <0.05）， and compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significantly greater improvements in the above indicators （all P <0.05）. In addition， compared with the hUC-MSC^OE-EV group， the hUC-MSC^Numb-OE group had significant improvements in the expression levels of liver regeneration-related markers （albumin and hepatocyte nuclear factor 4α） and the molecules associated with the Numb-p53 signaling axis （Numb， pNumb， Mdm2， and p53） （all P <0.05）. ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF， possibly by activating the Numb-PTB^L-p53-HNF4α axis， promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.

Hepatocellular carcinoma （HCC） is one of the most common malignant tumors with high incidence and mortality rates worldwide， which brings a huge burden to the physical and mental health and socio-economic life of patients. The adenosine monophosphate-activated protein kinase （AMPK） signaling pathway serves as the regulatory center of cellular energy metabolism and is closely associated with the biological activities of HCC cells， including autophagy， apoptosis， and angiogenesis， and it has become a hot topic in current cancer research. Traditional Chinese medicine drugs are abundant in natural components such as flavonoids， alkaloids， and phenols and have the characteristics of multiple targets， pathways， components， and hierarchies. By targeting the AMPK signaling pathway， these components can be used alone or in combination with conventional antitumor therapies to exert an anti-tumor effect on HCC from various aspects. This article reviews and summarizes the extracts of traditional Chinese medicine that target the AMPK signaling pathway for the prevention and treatment of HCC， in order to provide a theoretical basis and a reference for the clinical application of traditional Chinese medicine in the treatment of HCC and the development of related drugs.

According to TCM, the main pathogenesis of gastroesophageal reflux disease (GERD) is stomach disharmony and descending, and stomach qi ascending. Phlegm dampness and blood stasis are also important pathological factors of this disease. TCM treatment for GERD mainly starts from the liver, spleen and stomach. The basic treatment is to harmonize the stomach and lower the adverse, and to soothe the liver and relieve depression, invigorate the spleen and resolve dampness, promote qi and blood circulation, and clear heat and inhibit acid. Clinical treatment of GERD is mostly in the form of TCM compounds, often combined with Western medicine, which can improve symptoms, reduce recurrence rate and reduce adverse reactions. The mechanism is to inhibit gastric acid secretion, enhance lower esophageal sphincter pressure, promote gastrointestinal motility, inhibit inflammation, regulate esophageal visceral sensitivity and regulate intestinal flora.

Objective To analyze the epidemiological characteristics and temporal spatial clustering of hand, foot, and mouth disease in Hubei Province from 2010 to 2023, and to provide evidence for formulating prevention and control measures. Methods Descriptive epidemiological method was used to analyze the surveillance data of hand, foot, and mouth disease of Hubei Province from 2010 to 2023, and spatial clustering analysis was conducted at the district/county level using ArcGIS 10.5 software. Results A total of 1 007 600 cases of hand, foot, and mouth disease were reported from 2010 to 2023, and the average annual incidence rate was 123.60/100 000. Overall , it exhibited a cyclical pattern of high incidence every other year. Except for a few years, two peaks of incidence were observed each year, , with the first peak occurring between April to July and the second occurring in October to December, and the popular season was concentrated from April to July. Children aged < 5 years were primarily affected, with a high incidence in male patients (1.53:1). The incidence of hand, foot, and mouth disease showed a positive spatial autocorrelation（Moran's I was between 0.15 to 0.76, P<0.05）at the district/county level. The hot spots were concentrated in the northwest and southeast of Hubei Province, and the cool spots were concentrated in the east of central Hubei Province. Conclusion The incidence of hand, foot, and mouth disease has obvious seasonality and spatial clustering in Hubei Province. The key prevention and control areas are concentrated in the northwest and southeast of Hubei. Enhanced prevention and control measures should be targeted on children under 5 years old and key areas to effectively reduce the occurrence of cases.

Objective To construct a nomogram model for predicting the risk of in-hospital death in CHF patients by using noninvasive hemodynamic monitoring combined with age,DBP,CRP and renal insufficiency(serum creatinine≥ 442 μmol/L).Methods A total of 223 elderly patients with acute onset of CHF admitted in First,Second Medical Centre of Chinese PLA General Hos-pital from September 2022 to March 2023 were recruited in this study.According to their clinical outcomes,they were divided into survival group(196 cases)and death group(27 cases).Based on the in-hospital death and other related indicators,a nomogram model was constructed to predict the risk factors of in-hospital death in CHF.Results Noninvasive hemodynamic mornitoring indi-cated that the death group had significantly higher LVEF and LCWI values but lower LVEDV value than the survival group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that age(OR=1.131,95％CI:1.052-1.213,P=0.001),DBP(OR=0.932,95％CI:0.882-0.982,P=0.011),CRP(OR=1.171,95％CI:1.021-1.352,P=0.024),LVEDV(OR=0.984,95％CI:0.962-0.992,P=0.011)and renal insufficiency(OR=5.863,95％CI:1.351-1.731,P=0.004)were independent risk factors for the short-term prognosis of the elderly CHF patients.The AUC value of the nomogram model was 0.902(95％CI:0.819-0.948,P＜0.05),and calibration curve analysis showed the C-index was 0.902,indicating accurate predictive perform-ance.Conclusion Age,DBP,LVEDV,CRP and renal insufficiency are independent risk factors for the short-term prognosis of the elderly CHF patients.

Objective:To investigate the clinical characteristics and prognosis of neonatal chylothorax.Methods:The clinical data of newborns diagnosed with chylothorax from June 2016 to June 2023 in Neonatal Center of Beijing Children's Hospital were retrospectively analyzed, and divided into congenital group and acquired group according to the pathogenesis of chylothorax. The clinical characteristics, treatment methods and prognosis of the two groups were compared.Results:A total of 23 cases were included, including 17 cases (73.9%) in the congenital group and 6 cases (26.1%) in the acquired group. There was no significant difference in gender, gestational age and birth weight between the two groups ( P>0.05). Compared with the acquired group, the proportion of lymphocytes (97.0% vs. 85.0%), the use of erythromycin (7/17 vs. 1/6) and octreotide (9/17 vs. 1/6) and special formula milk feeding (13/17 vs. 2/6) were higher in the congenital group; the proportion of right hydrothorax (1/17 vs. 3/6), invasive mechanical ventilation (6/17 vs. 6/6) and breastfeeding (0/17 vs. 3/6) were lower in the congenital group ( P<0.05). There were no significant differences in terms of the white blood cell count in pleural fluid and plasma protein content, incidence of bilateral and left pleural fluid, proportion of closed thoracic drainage, maximum daily drainage volume, drainage duration, total drainage volume, albumin utilization rate, length of stay and survival rate between the two groups ( P>0.05). 18 cases of pleural effusion absorption without recurrence after conservative treatment; 5 cases died, of which 4 cases died after their parents abandoned treatment, and 1 case died of neonatal necrotizing enterocolitis after thoracic duct ligation surgery. Conclusions:Congenital chylothorax and acquired chylothorax were similar in severity, course of disease and overall prognosis. The utilization rate of erythromycin and octreotide in congenital chylothorax was higher than that in acquired chylothorax. The neonatal chylothorax is usually with an overall good 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.

Objective:To carry out genetic analysis on two families with carriers of small terminal translocations using karyotyping analysis and genomic copy number variation sequencing (CNV-seq).Methods:Two couples undergoing prenatal diagnosis at the Tianjin Central Hospital of Obstetrics and Gynecology respectively on April 12, 2020 and December 17, 2021 were selected as the study subjects. With informed consent, amniotic fluid and peripheral blood samples were collected and subjected to conventional karyotyping and CNV-seq analysis for the detection of chromosomal microdeletion/duplications.Results:Both couples had given births to children with chromosomal aberrations previously, and both fetuses were found to have abnormal karyotypes. CNV-seq showed that they had harbored microdeletion/duplications, and their mothers had both carried balanced translocations involving terminal fragments of chromosomes.Conclusion:For fetuses with small chromosomal segmental abnormalities, their parental origin should be traced, and the diagnosis should be confirmed with combined genetic techniques.

Oromucosal drug delivery preparations offer advantages such as convenient administration,suitability for patients with dysphagia,rapid onset of action,and avoidance of first-pass metabolism in the liver.The 2020 edition of the Chinese Pharmacopoeia,EP11.0,BP2022,USP44-NF39,and JP18 all include relevant standards for the quality control of different oromucosal drug delivery systems.This article compares the differences in general re-quirements for oromucosal formulations among different countries and provides an overview of inspection items for marketed oral mucosal formulations and those documented in pharmacopoeias both domestically and internationally.Foreign pharmacopoeias include a wide range of oromucosal drug delivery formulations,with more refined quality control measures for systemic action.These findings can serve as a reference for the improvement and enhancement of standards for oromucosal drug delivery systems in China.

Purpose To investigate the diagnostic value of postsystolic shortening in ischemia with non-obstructive coronary arteries(INOCA).Materials and Methods A total of 85 INOCA patients admitted to People's Hospital of Liaoning Province from May 2020 to December 2022 were selected and divided into two groups according to the ratio of distal diastolic average blood velocity of left anterior descending branch before and after treatment obtained by thymosidine load echocardiography(coronary flow velocity reserve,CFVR):CFVR<2.0 was in the coronary microvascular dysfunction(CMD)group(n=40),and CFVR≥2.0 was in the control group(n=45).Conventional echocardiographic parameters of all enrolled subjects were measured:left ventricular end-diastolic diameter index(LVEDDI),left ventricular end-diastolic volume index(LVEDVI),left ventricular end-systolic volume index(LVESVI),left ventricular ejection fraction(LVEF),early and late mitral valve diastolic blood flow velocity(E,A),E/A,average velocity of mitral valve annulus and interventricular septum in early diastolic(e')and E/e'on the wall and septal side were measured.The global longitudinal strain(GLS)and the post systolic index(PSI)of the left ventricle were measured by two-dimensional speckle tracking automated functional imaging.The differences of echocardiographic parameters,GLS and PSI between CMD group and control group were observed.The relationship between CFVR and PSI in CMD group was analyzed.Results There were no significant differences in LVEDDI,LVEDVI,LVESVI,LVEF,E,A,E/A,e',E/e'and GLS between control group and CMD group(t=-0.577-1.472,P>0.05).There was a statistically significant difference in PSI increase between CMD group and control group(t=-5.370,P<0.05).There was a good correlation between CFVR and PSI in CMD group(r=-0.486,P<0.05).The receiver operator characteristic curve showed that the area under the curve predicted by PSI for CMD was 0.786,the sensitivity was 68.0%,and the specificity was 77.8%.Conclusion PSI has good application value in evaluating left ventricular systolic function in INOCA patients,and can detect left ventricular systolic function injury in such patients at an early stage.