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 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 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 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.

BACKGROUND:Platelet-rich fibrin(PRF)is a second generation platelet concentrate with the advantages of simple operation,no anticoagulant,and high bioactivity,which has been applied in the fields of trauma repair,bone defect repair,and tendon soft tissue repair,and has been proved to have a certain tissue repair-promoting effect. OBJECTIVE:To study the repair effect of PRF on articular cartilage tissue in rats with knee osteoarthritis. METHODS:Thirty-six Sprague-Dawley rats were randomly divided into normal group,model group,and PRF group,with 12 rats in each group.Rats in the normal group did not undergo any treatment.In the model group,animal models of knee osteoarthritis were prepared and rat models were then given physiological saline into the joint cavity once a week after surgery.Rat models of knee osteoarthritis were also prepared in the PRF group,and autologous PRF was injected into the joint cavity once a week after surgery.After 5 weeks of continuous treatment,tissue samples were taken.Hematoxylin-eosin staining was used to observe the morphology of cartilage tissue.Tunel staining was used to detect chondrocyte apoptosis,ELISA was used to detect inflammatory factor levels.Western blot and RT-PCR were used to detect Bcl-2,Bax,and Caspase-3 expression in protein and mRNA levels,respectively. RESULTS AND CONCLUSION:The model group had severe cartilage tissue damage,while the PRF group had significantly improved cartilage tissue morphology compared with the model group.The model group had more apoptotic chondrocytes.Compared with the model group,the mean absorbance of Tunel positive staining in the PRF group significantly decreased(P<0.01).The levels of interleukin-1β,interleukin-6 and tumor necrosis factor-α were significantly increased in the model group and PRF group compared with the normal group(P<0.01)and were significantly decreased in the PRF group compared with the model group(P<0.01).The relative expressions of Bax and Caspase-3 at protein and mRNA levels were significantly increased in the model group and PRF group compared with the normal group(P<0.01),while the relative expressions of Bcl-2 at protein and mRNA were significantly decreased(P<0.01).Compared with the model group,the relative expression of Bax and Caspase-3 at protein and mRNA levels were significantly decreased in the PRF group(P<0.01),while the relative expressions of Bcl-2 at protein and mRNA levels were significantly increased(P<0.01).To conclude,PRF can inhibit chondrocyte apoptosis by inhibiting the expression of pro-inflammatory factors,thereby promoting cartilage tissue repair in knee osteoarthritis rats.

Objective: To investigate the dietary lead exposure level among children aged 3 to 4 years in Jiading District, Shanghai Municipality, and assess the health risk caused by lead exposure, so as to provide the basis for the management of children's food safety. Methods: Based on the 2023 Dietary and Health Status Surveillance Project in Jiading District, children aged 3 to 4 years from 12 streets (townships) in Jiading District were selected as the subjects using a multi-stage stratified random sampling method. The consumption frequency and daily intake of seven subcategories of four major food groups (beans, tofu), cereals (wheat, rice), meat (animal viscera), and aquatic products (mantis shrimps, bivalves) consumed by children over the past three months were collected using a food frequency questionnaire. Food samples were collected according to the food safety risk monitoring plan in Jiading District, and the lead content was detected. The health risks of dietary lead exposure among 3-4-year-old children were quantitatively assessed using the single-factor pollution index method, the Nemerow comprehensive pollution index method, and the margin of safety (MOS) method. Results: A total of 143 3-4-year-old children were surveyed, including 69 boys (48.25%) and 74 girls (51.75%). A total of 317 food samples were tested, and lead was detected in all seven subcategories of food samples, with an overall detection rate of 77.29%. The detection rates of lead in bivalves and mantis shrimps of aquatic products were relatively high (98.75% and 100.00%, respectively). The mean lead content of various foods ranged from 0.003 4 to 0.090 7, with the highest level found in bivalves. The lead content of all food samples did not exceed the standard. The single-factor pollution index of seven subcategories ranged from 0.017 2 to 0.148 0, and the Nemerow comprehensive pollution index ranged from 0.116 5 to 0.424 4, both of which were less than 0.7. The MOS (mean) ranged from 0.000 3 to 0.003 9, with an overall MOS (mean) of 0.012 2. The MOS (P95) ranged from 0.005 7 to 0.055 9, with an overall MOS (P95) of 0.112 4, both of which were less than 1. Conclusions The lead pollution level in the diet among children aged 3 to 4 years in Jiading District is safe and clean, with an acceptable impact on food safety. However, the detection rate of lead is relatively high, and the main source of dietary lead exposure is aquatic products.

Objective:To investigate the impact of the interval period between biopsy and MR examination on tumor detection and extraprostatic extension (EPE) assessment for prostate cancer (PCa) using multi-parametric MRI (mpMRI).Methods:The study was cross-sectional and retrospectively included 130 patients with PCa who underwent RP and preoperative systematic biopsies followed by mpMRI between January 2021 and December 2022 in the First Medical Center of Chinese PLA General Hospital. Patients were divided into 3 groups according to interval following biopsy (group A,<3 weeks, 31 cases; group B, 3-6 weeks, 67 cases; group C,>6 weeks, 32 cases). The percentages of hemorrhage volume in the total prostate were drawn on T 1WI and calculated. The junior, senior and expert radiologists independently localized the index lesions and calculated the accuracy for tumor detection, in addition to assessing the probabilities of EPE according to EPE grade. The correlation between the hemorrhage extent and interval was analyzed using the Spearman correlation coefficient. The accuracy for tumor detection was compared using χ2 test among groups. The diagnostic performance of the radiologists for EPE prediction was assessed using the receiver operating characteristic curve, and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. Results:The percentage of hemorrhage was correlated with the interval between biopsy and MR examination ( r=-0.325, P<0.001). The detection accuracy of junior radiologist was 83.9% (26/31), 76.1% (51/67), and 78.1% (25/32) in group A, B and C, respectively; no differences were observed in the detection accuracy among three groups ( χ2=0.76, P=0.685). The detection accuracy of senior radiologist was 83.9% (26/31), 80.6% (54/67), and 71.9% (23/32) in 3 groups with no differences ( χ2=1.53, P=0.464). The detection accuracy of expert radiologist was 80.6% (25/31), 77.6% (52/67), and 93.8% (30/32) with no differences ( χ2=3.95, P=0.139). The AUC (95% CI) for predicting EPE were 0.830 (0.652-0.940), 0.704 (0.580-0.809), 0.800 (0.621-0.920) in the group A, B and C for junior radiologist; 0.876 (0.708-0.966), 0.768 (0.659-0.863), 0.896 (0.736-0.975) for senior radiologist; and 0.866 (0.695-0.961), 0.813 (0.699-0.895), 0.852 (0.682-0.952) for expert radiologist, respectively. No differences were observed among the subgroups in each radiologist ( P>0.05). Conclusion:The interval period does not significantly affect the detection accuracy and EPE assessment of PCa using mpMRI. There is probably no necessity for prolonged intervals following systematic biopsy to preserve the clarity of MRI interpretation for PCa.