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 evaluate the efficacy and safety of pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC).Methods:This was a prospective, single-arm, open label, phase 2 clinical study enrolling patients at the Cancer Hospital of the Chinese Academy of Medical Sciences with R/M HNSCC treated with pembrolizumab plus nab-paclitaxel and cisplatin or carboplatin. After six cycles of treatment, patients received pembrolizumab as maintenance therapy until disease progression or intolerable toxicity or completion of 35 cycles of treatment. The primary endpoint was objective response rate, and secondary endpoints included overall survival, progression-free survival, and safety profile. Efficacy was evaluated according to the response evaluation criteria in solid tumors 1.1, survival analysis was performed using the Kaplan-Meier method, and adverse events were assessed using the America National Cancer Institute Common Terminology Criteria for Adverse Events 5.0.Results:A total of 30 patients with R/M HNSCC were enrolled from 23 April 2021 to 22 March 2023, including 28 males and 2 females, with a median age of 67 years. The median follow-up time was 14.5 months, the objective response rate was 70.0%, the disease control rate was 96.7%, and the median progression-free survival and overall survival of all patients were 11.6 months and 18.8 months, respectively. Median duration of response was up to 17.3 months. Grade≥3 treatment-related adverse events were leukopenia (26.7%), neutropenia (26.7%), peripheral neurotoxicity (3.3%), rash (3.3%), hyperalgesia (3.3%), and immune-related pneumonitis (3.3%). The most common immune-related adverse event was hypothyroidism (40.0%).Conclusion:Pembrolizumab combined with nab-paclitaxel and platinum shows encouraging antitumor activity accompanied with a manageable safety profile in untreated R/M HNSCC patients in China.

Objective To generate and identify the Itgbl1(integrin beta-like)promoter-driven Cre knock-in mouse line.Methods Itgbll-Cre knock-in mice were generated using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene editing.The Itgbl1-Cre mice were crossed with the Cre reporter ROSALSL-tdTomato)mice to detect the expression profile of Cre activity.The tdTomato expression pattern across tissues and cell-specific markers were used to identify the cell types of Itgbl1-expressing cells and their progeny.Results and Conclusion tdTomato was specifically expressed in mucous acinar cells of the sublingual gland,pancreatic islet cells,and gastric endocrine cells.In addition,tdTomato expression was also found in some of the neurons of the retina and brain,as well as in a few cells in the serosal layer of the intestine,articular cartilage,periosteum,and bone marrow.The first Itgbl1-Cre recombinase transgenic mouse line was established,which can specifically label the mucous acinar cells of the sublingual gland.

Objective:To investigate the orthodontic needs and to analyze the influencing factors of orthodontic treatment of university students in Xi'an.Methods:The orthodontic questionnaire survey was conducted in university students by stratified cluster random sampling,the Dental health component(DHC)and aesthetic component(AC)in the orthodontic treatment needs index were used as the objective indicators of orthodontic treatment needs,and the self-perceived aesthetic component(SAC)of the subjects was used as the subjective indicator of the need for orthodontic treatment.Univariate and multivariate logistic regression analysis were used to determine the influencing factors of university students'willingness to orthodontic treatment.Results:A total of 1135 university students were sur-veyed,including 578 males and 557 females.There were 224(19.74％),184(16.21％)and 120(10.57％)university students who required orthodontic treatment by DHC,AC and SAC analysis,respectively.Among the 224 university students who needed orthodontic treatment by DHC,68(30.36％)were willing to undergo orthodontic treatment,and 156(69.64％)were unwilling.Univariate and multivariate logistic regression analysis showed that gender,malocclusion,cognitive situation and social environment were independent influencing factors affecting the treatment intention.Conclusion:The objective orthodontic demand of Xi'an university students is high,but the demand for subjective orthodontic treatment is low.Gender,malocclusion,cognitive situation and social environment are the in-dependent influencing factors of university students'orthodontic treatment intention.

By reviewing the relevant literature of ancient herbal works and modern codices， this paper sorted out the historical evolution and developmental venation of processing of Notoginseng Radix et Rhizoma. On this basis， the modern research of processed products of Notoginseng Radix et Rhizoma was used as the breakthrough point to analyze the literature in terms of processing technology， chemical composition changes and changes in pharmacological effects before and after processing. According to the research status of processing of Notoginseng Radix et Rhizoma， some existing problems were analyzed in this paper， such as not many ancient processing methods used in modern time， lack of standardized research on processing technology. And saponins， polysaccharides， amino acids， flavonoids and other chemical components in Notoginseng Radix et Rhizoma may change to different degrees before and after processing， which was the main reason for the difference of efficacy before and after processing. However， the current research on the pharmacological effects of Notoginseng Radix et Rhizoma mainly focuses on raw products， resulting in a lack of in-depth research on the transformation mechanism of Notoginseng Radix et Rhizoma in processing difference， and the scientific connotation of "Shengxiao Shubu" has not been clearly elaborated， which is not conducive to the standardized clinical use of drugs. Therefore， it is necessary to further analyze the material basis of Notoginseng Radix et Rhizoma and its processed products， and to explore the change rule of chemical components before and after processing and its correlation with pharmacodynamic activity， so as to clarify the processing mechanism for providing scientific basis for its standardized processing， quality control and clinical rational use.

Objective:To investigate the role and mechanism of microRNA-499 (miR-499) regulating α-myosin heavy chain (α-MHC) and β-myosin heavy chain (β-MHC) gene axis in septic myocardial dysfunction (SMD) and its significance.Methods:Sixty healthy adult male Sprague-Dawley (SD) rats were divided into phosphate buffered saline (PBS) control group (PBS group), lipopolysaccharide (LPS) induced SMD model group (LPS group), miR-499 agonist pretreatment group (agomir+LPS group), and miR-499 inhibitor pretreatment group (antagomir+LPS group) by random number table, with 15 rats in each group. SMD rat model was reproduced by intraperitoneal injection of LPS 10 mg/kg. The PBS group was intraperitoneally injected with the same amount of PBS. The two pretreatment groups were injected with agomir 30 mg/kg or antagomir 80 mg/kg through the caudal vein for 3 days, once a day. PBS group and LPS group were not pretreated. Echocardiography was detected 5 hours after LPS injection, and relevant indexes were recorded. The expression of miR-499 in plasma and myocardial tissue was detected by real-time quantitative polymerase chain reaction (qPCR). Western blotting was used to detect the protein expressions of α-MHC and β-MHC in myocardial tissue. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of heart failure, was measured by electrochemiluminescence.Results:Compared with the PBS group, the rats in LPS group were depressed. Additionally, LPS down-regulated the level of miR-499 in plasma and myocardial tissue, decreased α-MHC expression in myocardial tissue and up-regulated the expression of β-MHC. Echocardiography showed that left ventricular ejection fraction (LVEF), left ventricle fractional shortening (LVFS), cardiac output (CO), stroke volume (SV) and heart rate (HR) decreased by 49.1%, 59.2%, 48.8%, 39.4% and 15.9%, respectively, and the level of plasma NT-proBNP increased significantly in LPS group, indicating that LPS could induce cardiac dysfunction in rats. Compared with the LPS group, after pretreatment with agomir to overexpress the miR-499, LVEF and LVFS were significantly increased [LVEF: 0.662±0.020 vs. 0.323±0.024, LVFS: (36.16±1.43)% vs. (20.20±1.32)%, both P < 0.01], which suggested that the cardiac function of rats was improved in agomir+LPS group. At the same time, pretreatment with agomir significantly down-regulated the β-MHC protein expression (β-MHC/GAPDH: 0.74±0.04 vs. 2.97±0.34, P < 0.01), significantly up-regulated α-MHC protein expression (α-MHC/GAPDH: 1.59±0.05 vs. 0.74±0.14, P < 0.01), and significantly decreased the plasma NT-proBNP level (ng/L: 114.49±6.85 vs. 334.13±4.36, P < 0.01). After pretreatment with antagomir to inhibit the expression of miR-499, echocardiography showed that LVEF and LVFS were significantly lower than those in the LPS group [LVEF: 0.297±0.021 vs. 0.323±0.024, LVFS: (19.38±1.52)% vs. (21.20±1.32)%, both P < 0.01], which suggested that the cardiac function of rats was significantly inhibited. At the same time, pretreatment with antagomir significantly down-regulated α-MHC protein expression in myocardial tissue (α-MHC/GAPDH: 0.63±0.03 vs. 0.74±0.14, P < 0.01), significantly up-regulated β-MHC protein expression (β-MHC/GAPDH: 3.03±0.47 vs. 2.97±0.34, P < 0.01), and significantly increased the level of plasma NT-proBNP (ng/L: 373.91±4.23 vs. 334.13±4.36, P < 0.05). Conclusions:miR-499 could regulate the expression of α-MHC and β-MHC which improved cardiac dysfunction caused by sepsis. Targeted regulation of miR-499 expression may be an effective way to treat SMD.

Objective:To analyze the survival rate of malignant tumor in the elderly over 60 years old in Qidong city from 1972 to 2016, and to provide basis for prognosis evaluation and prevention.Methods:Based on the data of 66 386 patients with malignant tumor in the elderly over 60 years old in the Qidong cancer registration and reporting system, the survival outcome was tracked by the method of active follow-up and passive follow-up.All of these data were then analyzed by stratification of sex, age, tumor site and hospital level.Results:During the period of 1972 to 2016, the total number of patients with malignant tumors in the elderly were 66 386 cases, accounting for 56.66% of patients in all age groups.The observed survival rate(OSR)of 5 and 10 years were 14.52% and 9.53% and relative survival rate(RSR)of 5 and 10 years were 19.76% and 18.92%, respectively, in the elderly in Qidong.The 5-year RSR was 16.98% for males and 23.91% for females, being a statistically significant( χ2=339.83, P<0.001). The 5-year RSRs of elderly patients in males and females increased from 7.53% and 15.83% in 1972-1976 to 28.06% and 39.01% in 2012-2016, respectively.The 5-year RSR of 60-64, 65-69, 70-74, 75-79, 80-84 and 85 years old and over were 22.84%, 20.53%, 17.74%, 18.30%, 18.02% and 14.06%, respectively, with a statistically significant difference( χ2=694.27, P<0.001). Among the top 10 major malignancies, the ranks of 5-year RSR from high to low were breast cancer, prostate cancer, bladder cancer, colorectal cancer, malignant lymphoma, gastric cancer, liver cancer, esophageal cancer, lung cancer, and pancreatic cancer, respectively.A comparison between 2002--2016 and 1972--1986 showed that the increased rank of absolute values of RSR from highest to lowest were prostate cancer, colorectal cancer, female breast cancer, bladder cancer, gastric cancer, malignant lymphoma, liver cancer, esophageal cancer, lung cancer, and pancreatic cancer, respectively.The 5-year RSR of patients diagnosed in the district / township hospitals, county hospitals, city-level 3A hospitals and provincial-level 3A hospitals were 13.97%, 23.71%, 26.12% and 28.55%, respectively, with a statistically significant difference( χ2=841.93, P<0.001). In the 45 years, the average annual percentage change(AAPC)ratio of 5-year OSR was 3.88%( t=6.75, P<0.001), and the 5-year RSR was 3.69%( t=7.44, P=0.001); the AAPC of the 5-year RSR was 3.91%( t=9.66, P<0.001)in males and 3.42%( t=6.08, P=0.001)in females.The AAPC ratio of 5-year RSR in each age group were 4.08% for 60-64 years, 4.18% for 65-69 years, 3.91% for 70-74 years, 3.12% for 75-79 years, 3.81% for 80-84 years, 0.51% for 85 years old and over, respectively.Except for age group of 85 years old and over( P=0.615), significant rising trends were observed in all age groups( P<0.01). Conclusions:Malignant tumors in the elderly have become the major cancer burden in Qidong, and there are significant gender and age differences.The overall survival rate in elderly patients with malignant tumors has been significantly improved in the past 45 years, which may be related to the improvement in the level of diagnosis and treatment and the service capacity of hospitals.

Objective:To explore a fast method to identify and confirm suspected clonorchis sinensis infection.Methods:For suspected clonorchis sinensis infection, the clonorchiasis serum antibody was detected first with ELISA. If the antibody was positive, the fecal examination for eggs was performed. If the fecal examination was negative, duodenal drainage under gastroscopy was recommended to detect eggs from the drainage fluid.Results:A total of 126 patients met the requirements and aged 54.14±13.33 (24- 87). There were 83 cases (65.87%, 83/126) with eggs positive in the drainage fluid, of which 53 cases were male, aged 55.91±11.47 (30-86), and 30 cases female, aged 55.87± 13.85(30-87). There was no significant difference in age between males and females( P>0.05). The time of catheterization (T1) of 126 cases was 3.79 ±1.45 min. The time of drainage (T2) of 126 cases was 31.39 ±14.29 min. There was no significant difference in T1 or T2 between the positive group and the negative group( P>0.05). The detection rates of eggs were 91.57% (76 cases) in intrahepatic bile duct drainage, 81.93% (68 cases) in the bile-cyst juice and 75.90% (63 cases) in the common bile duct fluid. No serious adverse reactions occurred during or after the operation. Conclusion:The detection rate of clonorchiosis sinensis can be effectively improved by the combination of clonorchiasis serum antibody test and gastroscopy-guided duodenal drainage.

Objective:To explore the application effect of optimizing diet management in patients with hyperphosphatemia.Methods:Seventy-seven patients who underwent regular hemodialysis in the blood purification department of the First Affiliated Hospital of Guangxi Medical University from September 2018 to June 2019 were selected. Patients were randomly divided into control group (39 cases) and intervention group (38 cases) by the method of random number table. The control group received routine nursing, while the intervention group received optimized dietary management intervention. The blood phosphorus, blood calcium, hemoglobin, albumin, dietary phosphorus related knowledge level and phosphorus control diet compliance of the two groups before and after the intervention were compared respectively.Results:After 3 months of intervention, the scores of knowledge about food phosphorus, compliance of phosphorus control diet and total score of the intervention group were (22.00±3.92), (34.82±4.69) and (56.82±7.48) points, which were higher than (18.46±3.57), (30.54±3.52) and (49.00±6.13) points of the control group, the difference was statistically significant ( tvalues were 4.146, 4.536 and 5.022, P<0.05). After 6 months of intervention, the scores of knowledge about food phosphorus, compliance of phosphorus control diet and total score of the intervention group were (25.74±3.36), (41.63±5.27) and (67.37±7.67) points, which were higher than (20.97±3.81), (32.36±4.38) and (53.33±6.80) points of the control group, the difference was statistically significant ( tvalues were 5.815, 8.403 and 8.504, P<0.05). After 3 months of intervention, the blood phosphorus level in the intervention group was 1.81 (1.67, 2.10) mmol/L, which was lower than 2.13 (1.87, 2.32) mmol/L in the control group, the difference was statistically significant ( Zvalue was-3.237, P<0.05). After 6 months of intervention, the blood phosphorus level in the intervention group was 1.75 (1.63, 1.91) mmol/L, which was lower than that in the control group 1.90 (1.83, 2.13) mmol/L, and the difference was statistically significant ( Zvalue was-3.343, P<0.01). Conclusion:Optimizing dietary management can improve patients' knowledge level of food phosphorus and dietary compliance of phosphorus control, effectively reduce blood phosphorus level, and have no obvious effect on nutritional status.

Objective:To evaluate the efficacy and safety of tazarotene/betamethasone dipropionate cream at different concentration ratios in the treatment of psoriasis vulgaris, and to determine the optimal drug concentration ratio for clinical use.Methods:A multicenter, randomized, double-blinded, multi-dose controlled study was conducted. From December 2008 to April 2009, a total of 180 patients with psoriasis vulgaris were enrolled from 7 research centers, such as Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College. These patients were randomly and equally divided into 5 groups: treatment groups 1, 2, 3, 4 treated with tazarotene/betamethasone dipropionate cream at concentration ratios of 0.025%/0.025%, 0.05%/0.025%, 0.025%/0.05% and 0.05%/0.05% respectively once a day, and control group treated with the cream vehicle once a day. The treatment lasted 4 weeks. Efficacy and safety were evaluated after 1, 2 and 4 weeks of treatment. One-way analysis of variance and least significant difference (LSD)- t test were used to compare measurement data among several groups, chi-square test and Fisher′s exact test to compare categorical data among groups, and Cochran-Mantel-Haenszel (CMH) test to compare psoriasis area severity index (PASI) response rates between groups. Results:After 4 weeks of treatment, 11 patients (30.56%) , 12 (33.33%) , 12 (33.33%) , 19 (52.78%) and 2 (5.56%) in the treatment groups 1, 2, 3, 4 and control group respectively achieved a 75% reduction in PASI (PASI75) , and the proportions of patients achieving PASI75 were significantly higher in the treatment groups than in the control group (all P < 0.012 7) . Additionally, the proportions of patients achieving PASI90 were also significantly higher in the treatment groups 1, 2 and 4 than in the control group (all P < 0.012 7) . After 4 weeks of treatment, the rates of reduction in PASI scores were 59.52% ± 26.79%, 57.19% ± 31.98%, 56.85% ± 30.46% and 68.21% ± 37.20% in treatment groups 1, 2, 3, and 4 respectively, which were all significantly higher than the rate of reduction in the control group (20.07% ± 28.55%; LSD- t = 5.36, 5.05, 5.00, 6.55, all P < 0.001) . The treatment group 4 showed marked comprehensive efficacy. All the tested drugs were well tolerated in the patients, and adverse reactions occurred in 11 (30.56%) , 8 (22.22%) , 2 (5.56%) , 4 (11.11%) and 2 (5.56%) cases in the treatment groups 1, 2, 3, 4 and control group respectively. The incidence rate of adverse reactions was significantly higher in the treatment group 1 than in the control group ( P = 0.012) , and there was no significant difference among the treatment groups 2, 3, 4 and control group (all P > 0.05) . Conclusion:The tazarotene 0.05%/betamethasone dipropionate 0.05% cream can be recommended for subsequent clinical trials in psoriasis vulgaris.