OBJECTIVE To explore the clinical efficacy of dapagliflozin for stable coronary heart disease combined with heart failure （HF）. METHODS A prospective study method was employed. A total of 158 patients with stable coronary heart disease and HF admitted to our hospital from January 1， 2023， to January 1， 2024， were enrolled. Using a random number table method， they were divided into dapagliflozin group （n＝76） and conventional treatment group （n＝82）. All patients received conventional treatment， including diuretic， aspirin， losartan， metoprolol and statins. Patients in the dapagliflozin group were additionally administered Dapagliflozin tablets at a dose of 10 mg once daily on top of the conventional treatment. The treatment duration was six months. The changes in left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， fasting blood glucose， N-terminal pro-brain natriuretic peptide （NT-proBNP）， the number of angina attacks， the duration of angina attacks， and lipoprotein-associated phospholipase A2 before and after treatment were compared between the two groups. The occurrence of adverse reactions such as renal dysfunction， liver dysfunction， urinary system infections， new-onset dialysis， hypotension and hypoglycemia was evaluated in the two groups during treatment. RESULTS During the study， 16 patients were lost to follow-up. Ultimately， 70 patients in the dapagliflozin group and 72 patients in the conventional treatment group completed the study. Before treatment， there were no statistically significant differences in the aforementioned indicators between the two groups （P＞0.05）. Compared with before treatment， after treatment， both groups showed significant shortening in LVESD and LVEDD， significant increases in LVEF， significant reductions in NT-proBNP and lipoprotein-associated phospholipase A2 levels， and significant reductions in the number of angina attacks and the duration of angina attacks （P＜0.05）； the improvements in the dapagliflozin group were more significant than those in the conventional treatment group （P＜0.05）. There was no statistically significant difference between the two groups in fasting blood glucose levels and the incidence of the aforementioned adverse reactions （P＞0.05）. CONCLUSIONS Adding dapagliflozin to conventional treatment can shorten LVESD and LVEDD， increase LVEF levels， reduce NT-proBNP and lipoprotein-associated phospholipase A2 levels， and decrease the number and duration of angina attacks in patients with stable coronary heart disease combined with HF， thereby improving their cardiac function， and demonstrates good safety.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Objective:To describe the trend of mortality and death spectrum in Shandong Province from 1970 to 2021 and provide basis for the targeted disease prevention and control.Methods:The data were collected from the death registration reports of Shandong and 3 national retrospective surveys of death causes in Shandong. The change in levels of overall and specific deaths in Shandong in different years were analyzed based on mortality rate, age-standardized mortality rate and constituent ratio of cause of death, differential decomposition was used to quantify the contribution of demographic and non-demographic factors to changes of mortality.Results:The crude mortality rate in residents in Shandong was basically stable from 1970 to 2021, and the mortality rate during 2020-2021 (732.73/100 000) was slightly higher than that during 1970-1974 (671.98/100 000). While the standardized mortality rate decreased significantly, and the mortality during 2020-2021 (183.39/100 000) decreased by 67.71% compared with that during 1970-1974 (568.00/100 000). The negative increase of population factors and the positive decrease of non-population factors reacted each other, so the mortality was relatively stable. Cardiac-cerebrovascular disease was always the leading cause of death, but the constituent ratio of death increased rapidly from 19.70% during 1970-1974 to 54.72% during 2020-2021. The rank in the causes of death changed from the fourth (11.46%) to the second (25.70%) for malignant tumor, from the seventh (5.85%) to the third (5.59%) for injury, from the second (12.87%) to the fourth (4.99%) for chronic respiratory diseases, from the third (12.27%) to the tenth (0.42%) for infectious diseases. The standardized mortality rates of the main causes of death decreased at different degrees, the standardized mortality rates of obstetrical disease, infectious disease, gastrointestinal disease and chronic respiratory disease decreased by more than 50.00%. The age distribution of deaths and the death spectrum in different age groups and in urban-rural populations changed significantly. During 2020-2021, the proportion of deaths in young people aged 0-14 years was 0.54%, which was 97.05% lower than that during 1970-1974, while the proportion of deaths in the elderly aged ≥75 years was 55.14%, which was 55.75% higher than that during 1970-1974. The rank of infectious diseases in the causes of death descended significantly in all age groups, but the ranks of injury, neuropsychiatric disease and malignant tumor rose significantly in adolescents, and the ranks of endocrine nutrition and metabolic disease rose in middle-aged and elderly people. The difference of death spectrum between urban area and rural area became less obvious and the main death causes in urban and rural residents were basically the same during 2020-2021.Conclusions:The death spectrum of residents in Shandong changed significantly. Chronic and non-communicable diseases, especially cardiac-cerebrovascular disease and malignant tumor, should be the focus in disease control and prevention. The prevention and control of diseases in Shandong made remarkable achievement during 1970-2021. However, in the context of population ageing, it is suggested to strengthen the treatment, prevention of diseases and injuries related to the health of the elderly and elderly health care in the future.

Objective:To analyze the dietary patterns of Chinese adults and explore the relationship with serum uric acid (SUA) and hyperuricemia (HUA).Methods:A total of 9 358 adults were selected in the 2018 China Health and Nutrition Survey. Dietary intake data were collected by three consecutive 24-hour dietary recalls and weighing method. The social demographic information of the survey subjects was obtained through questionnaire surveys. The dietary patterns were extracted using factor analysis, and the relationship between dietary patterns and SUA was analyzed using multiple linear regression analysis. The correlation between HUA and dietary patterns was analyzed using logistic regression analysis models.Results:Four dietary patterns were identified: northern (high intakes of wheat, other cereals,and tubers); modern (high intakes of fruit, dairy, eggs, and nuts); southern (high intakes of rice and vegetables);animal food-wine (high intake of organ meats, seafood, and wine). The multiple linear regression analysis results showed that the northern pattern was negatively correlated with SUA ( β=-0.438, 95% CI: -0.500--0.376); the modern pattern was negatively correlated with SUA ( β=-0.134, 95% CI: -0.219--0.049); the southern model was significantly correlated with higher SUA ( β=0.146, 95% CI: 0.079-0.214); the animal food-wine pattern was positively correlated with SUA ( β=0.188, 95% CI: 0.123-0.252). Logistic regression analysis showed that compared with the northern model score Q1 group, the risk of developing HUA was reduced in Q3 and Q4 groups, with ORs values of 0.777 (95% CI: 0.650-0.929) and 0.509 (95% CI: 0.423-0.613), respectively; and compared with the modern model score Q1 group, the higher the scores in Q3 and Q4 groups, the HUA was lower, with ORs of 0.793 (95% CI: 0.660-0.953) and 0.768 (95% CI: 0.631-0.934), respectively. Compared with the animal food-wine pattern score Q1 group, the risk of developing HUA was increased in both Q3 and Q4 groups ( Q3 group: OR=1.224, 95% CI: 1.012-1.480; Q4 group: OR=1.312, 95% CI: 1.086-1.584). Conclusions:Dietary patterns are associated with HUA. The northern and modern patterns are related to lower SUA levels and reduced risk of HUA, while the animal food-wine pattern increases the risk of HUA.

Objective:To evaluate the application effect of a new type of laparoscopic multi-degree-of-freedom surgical instrument in the training of basic surgical skills and analyze the learning curve.Methods:The teaching records of the trainees who received training in the training base of laparoscopic surgeons in Chinese People′s Liberation Army General Hospital from January to October, 2023 were collected. The 50 trainees were randomly divided into conventional instrumentation group and new instrumentation group with 25 trainees in each group according to the random number table method before the training. According to the research design, five modules such as "accurate bean clamping, plum blossom pile bean clamping, ferrule positioning, threading with both hands, sewing and knotting" were trained. After the training, they were assessed and the completion time of each module was recorded. The comparison of the changes of the completion time of the two groups of students before and after training was statistically analyzed by differences-in-differences(DID) method, and the fitting analysis of learning curve was analyzed by cumulative summation method .Results:Before the training, there was no statistically significant difference in the time required to complete five modules between the two groups of trainees (all P>0.05). After the training, the time to complete the five modules in both groups was reduced compared to before the training (accurate bean clamping: (63.7±9.3) seconds vs. (85.4±18.2) seconds, t=2.38, P=0.035; plum blossom pile bean clamping: (45.2±6.8) seconds vs. (103.1±57.2) seconds, t=8.77, P=0.047; ring positioning: (78.5±19.1) seconds vs. (126.2±26.3) seconds, t=6.96, P=0.019; threading with both hands: (63.3±21.2) seconds vs. (105.8±27.9) seconds, t=3.43, P=0.015; sewing and knotting: (160.2±79.5) seconds vs. (228.9±96.6) seconds, t=4.58, P=0.008).The average time required to complete the five modules was shorter in the new instrument group compared to the conventional instrument group (DID for accurate bean clamping=37.66, t=2.43, P=0.007; DID for plum blossom pile bean clamping=58.42, t=3.03, P=0.013; DID for ferrule positioning=28.33, t=2.83, P=0.031; DID for threading with both hands=48.89, t=2.10, P=0.042; DID for sewing and knotting=54.78, t=3.57, P=0.012). In the learning curves for the plum blossom pile bean clamping, ferrule positioning, and sewing and knotting modules, the new instrument group required fewer class hours to reach proficiency compared to the conventional instrument group (plum blossom pile bean clamping: 3 class hours vs. 4 class hours; ferrule positioning: 4 class hours vs. 5 class hours; sewing and knotting: 3 class hours vs. 5 class hours). In the accurate bean clamping and threading with both hands modules, both the conventional and new instrument groups crossed the learning curve at the 5 th class hour, but there was a statistically significant difference in the slopes of the curves between the two groups (accurate bean clamping: t=-2.85, P=0.004; threading with both hands: t=-2.66, P=0.008). Conclusion:The new type of laparoscopic multi-degree-of-freedom surgical instruments can improve the learning effect and shorten the learning curve in laparoscopic training teaching, which shows good application effect and has the possibility of clinical trial.

Objective:To evaluate the application effect of a new type of laparoscopic multi-degree-of-freedom surgical instrument in the training of basic surgical skills and analyze the learning curve.Methods:The teaching records of the trainees who received training in the training base of laparoscopic surgeons in Chinese People′s Liberation Army General Hospital from January to October, 2023 were collected. The 50 trainees were randomly divided into conventional instrumentation group and new instrumentation group with 25 trainees in each group according to the random number table method before the training. According to the research design, five modules such as "accurate bean clamping, plum blossom pile bean clamping, ferrule positioning, threading with both hands, sewing and knotting" were trained. After the training, they were assessed and the completion time of each module was recorded. The comparison of the changes of the completion time of the two groups of students before and after training was statistically analyzed by differences-in-differences(DID) method, and the fitting analysis of learning curve was analyzed by cumulative summation method .Results:Before the training, there was no statistically significant difference in the time required to complete five modules between the two groups of trainees (all P>0.05). After the training, the time to complete the five modules in both groups was reduced compared to before the training (accurate bean clamping: (63.7±9.3) seconds vs. (85.4±18.2) seconds, t=2.38, P=0.035; plum blossom pile bean clamping: (45.2±6.8) seconds vs. (103.1±57.2) seconds, t=8.77, P=0.047; ring positioning: (78.5±19.1) seconds vs. (126.2±26.3) seconds, t=6.96, P=0.019; threading with both hands: (63.3±21.2) seconds vs. (105.8±27.9) seconds, t=3.43, P=0.015; sewing and knotting: (160.2±79.5) seconds vs. (228.9±96.6) seconds, t=4.58, P=0.008).The average time required to complete the five modules was shorter in the new instrument group compared to the conventional instrument group (DID for accurate bean clamping=37.66, t=2.43, P=0.007; DID for plum blossom pile bean clamping=58.42, t=3.03, P=0.013; DID for ferrule positioning=28.33, t=2.83, P=0.031; DID for threading with both hands=48.89, t=2.10, P=0.042; DID for sewing and knotting=54.78, t=3.57, P=0.012). In the learning curves for the plum blossom pile bean clamping, ferrule positioning, and sewing and knotting modules, the new instrument group required fewer class hours to reach proficiency compared to the conventional instrument group (plum blossom pile bean clamping: 3 class hours vs. 4 class hours; ferrule positioning: 4 class hours vs. 5 class hours; sewing and knotting: 3 class hours vs. 5 class hours). In the accurate bean clamping and threading with both hands modules, both the conventional and new instrument groups crossed the learning curve at the 5 th class hour, but there was a statistically significant difference in the slopes of the curves between the two groups (accurate bean clamping: t=-2.85, P=0.004; threading with both hands: t=-2.66, P=0.008). Conclusion:The new type of laparoscopic multi-degree-of-freedom surgical instruments can improve the learning effect and shorten the learning curve in laparoscopic training teaching, which shows good application effect and has the possibility of clinical trial.

Objective To investigate the expression of lncRNA SNHG8 in placenta accrete(PA)and its effect on trophoblast invasion and migration.Methods qRT-PCR was used to detect the expression of lncRNA SNHG8 in placenta tissue of 30 cases in PA group and 30 cases in control group,and the correlation between lncRNA SNHG8 expression and prenatal ultrasound score of 30 cases in PA group was analyzed.Transwell and scratch assay were used to detect the effect of lncRNA SNHG8 interference on the invasion and migration of human chorionic trophoblast cells(HTR8/SVneo cells),and western blot was used to detect the expression of MMP-2 and MMP-9.The downstream targets of lncRNA SNHG8 were predicted by StarBase software,and the expression of lncRNA SNHG8 was detected in placental tissues of the two groups.Dual luciferase reporter assay was used to detect the targeting relationship between lncRNA SNHG8 and miR-542-3p.Results Compared with that of the control group,the expression of lncRNA SNHG8 was up-regulated in the placenta tissue of the PA group(P<0.05),and it was positively correlated with prenatal ultrasound score.Interference with lncRNA SNHG8 inhibited the invasion and migration of trophoblast cells(P<0.05);the protein expression of MMP-9 and MMP-2 also decreased signifi-cantly(P<0.05).Biological prediction indicates that miR-542-3p had a binding site with lncRNA SNHG8,and miR-542-3p expression was down-regulated in PA placental tissue(P<0.05).Dual luciferase reporter assay confirmed that lncRNA SNHG8 could target miR-542-3p.Compared with si-SNHG8+inhibitor-NC,co-transfection of si-SNHG8 and miR-542-3p inhibitor enhanced the invasion and migration ability of trophoblast cells(P<0.05).Conclusion lncRNA SNHG8 is highly expressed in PA and is related to the severity of PA.LncRNA SNHG8 promotes the invasion and migration of trophoblast by regulating the level of miR-542-3p.The study suggests that lncRNA SNHG8 plays an important role in the invasion and migration of PA trophoblast cells,which is expected to be a clinical diagnostic biomarker and therapeutic target.

Objective To explore the clinical efficacy of alirocumab combined with ybutimibe in acute ST segment elevation myocardial infarction(STEMI).Methods A total of 112 cases of STEMI patients were randomly divided into control group and study group,with 56 cases in each.All patients underwent PCI treatment after admis-sion.The control group received oral administration of atorvastatin after the surgery,while the study group received combined treatment of atorvastatin with alirocumab.After 6 months of maintenance treatment,the low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides,total cholesterol,left ventricular ejection fraction(LVEF),early and late diastolic peak flow velocity ratio(E/A)of the mitral valve orifice,left ventricular end-systolic diameter(LVESD),N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac troponin I(cTnI),lipoprotein-associated phospholipase A2(Lp-PLA2),matrix metalloproteinase-9(MMP-9),interleukin-6(IL-6),thrombolysis in myocardial infarction(TIMI)flow grade,drug toxicity,and postopera-tive cardiovascular adverse events were compared between the two groups.Results After treatment,the level of LDL-C,triglycerides,and total cholesterol in both groups decreased,and more significant results were found inthe study group(P＜0.05).There was no significant difference in HDL-C between the two groups before and after treatment(P＞0.05).After treatment,LVEF and E/A in both groups increased,with more significantresults in the study group(P＜0.05).LVESD,NT-proBNP,cTnI,Lp-PLA2,MMP-9,and IL-6 in both groups decreased after treatment,with more significant resultsin the study group(P＜0.05).The proportion of TIMI Ⅲ grade in the study group was higher than that in the control group(P＜0.05),and there was no significant difference in the incidence of drug adverse reactions and postoperative cardiovascular adverse events between the two groups6 months after surgery(P＞0.05).Conclusion The combination of alirocumab and ybutimibe in the treatment of STEMI PCI patients is more helpful in reducing blood lipid levels,promoting blood flow perfusion and improving myocardial function,and has good safety.

Objective:To explore the relationship between relapse tendency and psychological craving in fe-male methamphetamine(MA)-dependent young adults,focusing on the roles of self-control and future time per-spective.Methods:A total of 340 MA-dependent young adults from two women's compulsory isolation drug reha-bilitation centers in Sichuan Province were included.Participants were assessed with the Relapse Tendency Ques-tionnaire(RTQ),Obsessive Compulsive Drug Use Scale(OCDUS),Drug Abuser Self-Control Ability Question-naire(DASAQ)and General Future Time Perspective Scale(GFTPQ).The moderated mediation model was ana-lyzed by using the SPSS macro program PROCESS(version4.2).Results:The RTQ scores were positively correla-ted with the OCDUS scores(r=0.45,P＜0.001).The DASAQ scores partially mediated the relationship between the scores of OCDUS and RTQ,accounted for 37.91％of the total effect.The GFTP scores moderated the relation-ship between the scores of the OCDUS,DASAQ and RTQ(β=-0.18,0.19,P＜0.001).Conclusion:The influ-ence of psychological craving on relapse tendency in female MA-dependent young adults exhibits a moderated me-diating effect,suggesting the potential of enhancing self-control and future time perspective for preventing relapse and improving detoxification efficiency.