BACKGROUND: The beneficial effects of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on adverse cardiac outcomes in diabetic patients are well-established. However, the effects of SGLT2i against cancer therapy-related cardiotoxicity remain understudied. We investigated the association between SGLT2i and cardiac outcomes in cancer patients. METHODS: PubMed, Embase, and the Cochrane Library were searched from their inception until September 30, 2024 for studies evaluating the effects of SGLT2i in patients with cancer. The primary outcomes included incident heart failure (HF), HF exacerbation, HF hospitalization, atrial fibrillation/atrial flutter (AF/AFL), myocardial infarction, and all-cause mortality. The secondary outcomes included acute kidney injury and sepsis. Odds ratio (OR) with 95% CI was pooled. RESULTS: Thirteen studies with 85,596 patients were included. Compared to non-SGLT2i use, SGLT2i treatment was associated with lower risks of incident HF (OR = 0.51, 95% CI: 0.32-0.79, P = 0.003), HF exacerbation (OR = 0.74, 95% CI: 0.63-0.87, P < 0.001), AF/AFL (OR = 0.67, 95% CI: 0.55-0.82, P < 0.001), myocardial infarction (OR = 0.61, 95% CI: 0.41-0.90, P = 0.01), and all-cause mortality (OR = 0.44, 95% CI: 0.28-0.69, P < 0.001), but not for HF hospitalization (OR = 0.58, 95% CI: 0.22-1.55, P = 0.28). As for safety outcomes, SGLT2i use was associated with lower risks of acute kidney injury (OR = 0.68, 95% CI: 0.57-0.81, P < 0.001) and sepsis (OR = 0.32, 95% CI: 0.23-0.44, P < 0.001). CONCLUSIONS SGLT2i were associated with lower risks of incident HF, HF exacerbation, AF/AFL, myocardial infarction, all-cause mortality, acute kidney injury, and sepsis in cancer patients.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective To observe the effect of parecoxib sodium combined with dexmedetomidine preemptive analgesia on postoperative analgesia in patients with modified radical mastectomy for breast cancer.Methods Patients who underwent modified radical mastectomy for breast cancer were randomly divided into control group and treatment group based on simple binary randomization by random number table method.In the control group,"0.05 mg·kg-1 midazolam+1.0-1.5 mg·kg-1 propofol+0.4 μg·kg-1sufentanil citrate+0.15 mg·kg-1 phenylsulfonyl cisatracurium"was used for induction and maintenance of anesthesia.In the treatment group,the induction and maintenance of anesthesia was performed with the protocol of"parecoxib sodium 40 mg+dexmedetomidine 0.5 μg·kg-1·h-1)continuous pumping"on the basis of control group,and mechanical ventilation was performed by tracheal intubation 5 min after induction.The effect of pre-analgesia,postoperative sedation,hemodynamic indexes,surgical improvement indexes and application safety were observed by groups.Results There were 46 patients in each group.Pain visual analogue scores at 6,12 and 24 h in treatment group were 2.09±0.72,4.17±1.07 and 4.07±1.05,lower than those in control group,which were 2.61±1.03,4.76±1.27 and 4.65±1.11,the differences were statistically significant(all P＜0.05).The Ramsay sedation scores of the treatment group and the control group at 6 h after surgery were(2.85±0.62)and(2.11±0.73)points,respectively;the sedation scores of Ramsay at 12 h were 1.41±0.28 and 1.06±0.15,respectively.At 24 h,the sedation scores of Ramsay were 1.15±0.18 and 0.64±0.13,respectively,and the difference was statistically significant(P＜0.05).HR and MAP of treatment group and control group at T2 and T3 were significantly lower than those at T1 and T0(P＜0.05),there were no difference in HR and MAP between treatment group and control group at T2 and T3(P＜0.05).Operation time,recovery time after operation and intraoperative blood loss in treatment group were significantly lower than those in control group,and the differences were statistically significant(all P＜0.05).The success rate of 12-hour postoperative analgesia in test group and control group was 82.61％(38 cases/46 cases)and 63.04％(29 cases/46 cases),respectively,and the difference was statistically significant(P＜0.05).The adverse drug reactions in treament group and control group mainly included bradycardia,headache,dizziness and nausea,and the incidence of adverse drug reactions in treatment group and control group were 13.04％(6 cases/46 cases)and 8.70％(4 cases/46 cases),respectively,the difference was no statistically significant(P＜0.05).Conclusion Parecoxib sodium combined with dexmedetomidine preemptive analgesia has significantly improved analgesia and sedative effects in modified radical mastectomy for breast cancer,can prolong sedation and analgesia time,and stably control the perioperative hemodynamics of patients.

Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete Nocardia brasiliensis IFM 0406, has become a novel immunosuppressant candidate due to its significant immunosuppressive activity, low toxicity and unique mechanism of action. However, brasilicardin A and its analogues have become a research hotspot to the development of this promising immunosuppressant because of the low-yield production in the natural pathogenic producer and the synthetically challenging skeleton. According to the reported biosynthetic pathway of brasilicardin A, the function of involved diterpene synthase was analyzed by bioinformatics. Then the genes bra1-5 that synthesize the brasilicardin A skeleton were directionally amplified from the pathogenic strain N. brasiliensis IFM 0406, and heterologous expression was achieved successfully in Streptomyces albus R1. The compounds were isolated and purified by using various column chromatographies including silica gel column chromatography and semi-preparative HPLC. Six new brasilicardins were established and named brasilicardin H-M. The activity of brasilicardins was screened using lipopolysaccharide (LPS)-activated mouse primary macrophage inflammation model. Brasilicardin H-M exhibited good inhibitory activity on nitric oxide (NO) release with IC₅₀ values of 28.24 ± 3.70, 37.44 ± 2.00, 39.85 ± 4.02, 26.77 ± 4.40, 65.25 ± 1.48 and 15.24 ± 2.72 μmol·L^-1, respectively (indomethacin as the positive control with IC₅₀ value of 34.28 ± 4.10 μmol·L^-1). The results indicated that six compounds had potential anti-inflammatory activity. This study laid a foundation for the elucidation of the brasilicardin A biosynthetic pathway and evaluation of the structure-activity relationship as well as new drug developments.

Objective:To evaluate the effects of fine particle matter(PM2.5)and ozone(O3)com-bined exposure on adenosine triphosphate(ATP)amount and ATPase activities in nasal mucosa of Spra-gue Dawley(SD)rats.Methods:Twenty male SD rats were divided into control group(n=10)and exposure group(n=10)by random number table method.The rats were fed in the conventional clean environment and the air pollutant exposure system established by our team,respectively,and exposed for 208 d.During the exposure period,the concentrations of PM2 5 and O3 in the exposure system were moni-tored,and a comprehensive assessment of PM2 5 and O3 in the exposure system was conducted by combi-ning self-measurement and site data.On the 208 d of exposure,the core,liver,spleen,kidney,testis and other major organs and nasal mucosal tissues of the rats were harvested.Each organ was weighed and the organ coefficient calculated.The total amount of ATP was measured by bioluminescence,and the ac-tivities of Na+-K+-ATPase and Ca2+-ATPase were detected by spectrophotometry.The t test of two inde-pendent samples was used to compare the differences among the indicator groups.Results:From the 3rd week to the end of exposure duration,the body weight of the rats in the exposure group was higher than that in the control group(P＜0.05),and there was no significant difference in organ coefficients be-tween the two groups.The average daily PM2 5 concentration in the exposure group was(30.68±19.23)μg/m3,and the maximum 8 h ozone concentration(O3-8 h)was(82.45±35.81)μg/m3.The chemi-luminescence value(792.4±274.1)IU/L of ATP in nasal mucosa of the rats in the exposure group was lower than that in the control group(1 126.8±218.1)IU/L.The Na+-K+-ATPase activity(1.53±0.85)U/mg in nasal mucosa of the rats in the exposure group was lower than that in the control group(4.31±1.60)U/mg(P＜0.05).The protein content of nasal mucosa in the control group and the exposure group were(302.14±52.51)mg/L and(234.58±53.49)mg/L,respectively,and the ac-tivity of Ca2+-ATPase was(0.81±0.27)U/mg and(0.99±0.73)U/mg,respectively.There was no significant difference between the groups.Conclusion:The ability of power capacity decreased in the rat nasal mucossa under the sub-chronic low-concentration exposure of PM2 5 and O3.

Objective To investigate the risk factors for delayed union of extra-articular fractures of the middle and lower third of the tibia treated by locking plate.Methods Total of 135 patients of extra-articular fractures of the middle and lower third of the tibia from January 2013 to December 2018 were retrospectively analyzed,including 85 males and 50 females,ranged from 19 to 80 years old.All cases were treated with locking plates.The patients were divided into union group and delayed union group ac-cording to the condition of fracture union.The risk factors of delayed healing were determined by univariate analysis of 14 factors that might affect fracture healing first,then the factors with significance were analyzed by binary Logistic regression.Results There were 13 patients of delayed union,and the rate of delayed union was 9.63％.Univariate analysis showed that delayed union was associated with age,smoking,reduction method,anemia and time of preoperative preparation.Regression analysis showed thatage[OR=0.849,95％CI(0.755,0.954),P=0.006],smoking[OR=0.020,95％CI(0.002,0.193),P=0.001],reduction method[OR=23.924,95％CI(2.210,258.943),P=0.009],anemia[OR=0.016,95％CI(0.001,0.289),P=0.005]were the con-tributory factors for delayed union.Conclusion Young age,smoking,closed reduction and anemia are the risk factors for de-layed union of extra-articular fractures of the middle and lower third of the tibia treated by locking plate.

Tricuspid regurgitation(TR)is a common heart valve disease traditionally treated with surgery,which is invasive and high-risk.Recently,transcatheter tricuspid valve intervention(TTVI)technology has achieved major breakthroughs.It is being promoted internationally and several expert consensus documents have been launched abroad.However,in China,there is still a lack of consensus documents in this regard.In order to promote the safe,standardized and healthy development of this technology,this expert consensus is specially compiled.This consensus will introduce anatomy,epidemiology,classification and pathogenesis of TR,the traditional treatment and TTVI,preoperative evaluation and clinical efficacy endpoints.We sort out ten core viewpoints so that readers can quickly grasp the essence of the consensus.

Transcatheter aortic valve replacement(TAVR)has reached maturity and has entered a stage of steady and stable development in China.From 2017 to 2023,the number of centers conducting TAVR in China has increased from less than 10 to over 600,and the annual implantation volume has increased from hundreds to over 10 000.The 2018 and 2021 editions of the"Expert Consensus on Clinical Pathway for Transcatheter Aortic Valve Replacement in China"played a crucial guiding role during the golden period of TAVR development in China.With significant progress in evidence-based practice,clinical experience,guideline updates,device development,and procedure technique improvements in the TAVR field,especially the important advances in technologies developed from China,protocol optimization based on Chinese clinical practices,it is necessary to update the previous clinical pathway consensus.The new version of the clinical pathway expert consensus has updated the standard procedures for preoperative clinical assessment,perioperative imaging evaluation,standardized procedural processes,comprehensive perioperative management,and postoperative rehabilitation follow-up for TAVR patients.This update aims to further promote the healthy and standardized development of TAVR technology in China and to steadily enhance the medical and scientific research capabilities with this therapeutic technology.

Objective:To explore the regional differences,spatial correlation and influencing factors of the supply level of public health resources in China from 2012 to 2021,and to provide reference for optimising the allocation of public health resources.Methods:The entropy method was used to measure the comprehensive score of the level of supply of public health resources,and the Dagum Gini coefficient and spatial autocorrelation model were used to analyze the regional differences and spatial correlation of the supply level,and combined with the regression model of the panel data,the factors affecting the level of supply were explored.factors.Results:From 2012 to 2021,the supply level of public health resources in China showed an overall upward trend,but there were significant inter-provincial differences,presenting an"east low,west high"pattern.Regional disparities were the main reason for the national imbalance in supply levels.The spatial autocorrelation model showed a significant positive correlation in the supply level,with a distribution characterized by high-high and low-low agglomeration.The increase of financial autonomy has a promoting effect on the improvement of the supply level of public health resources.Conclusion:China should focus on narrowing the regional disparities in the supply level of professional public health resources,changing the pattern of"east low,west high",and promoting the synergistic development within and outside the region.Local governments should increase their financial autonomy and decide on the allocation and management of public health resources according to the actual situation of the region,soasto improve the level of public health resource supply.

Purpose: To intelligently diagnose whether there is bladder outlet obstruction (BOO) in female with decent detrusor contraction ability by focusing on urodynamic study (UDS) data. Materials and Methods: We retrospectively reviewed the UDS data of female patients during urination. Eleven easily accessible urinary flow indicators were calculated according to the UDS data of each patient during voiding period. Eight diagnosis models based on back propagation neural network with different input feature combination were constructed by analyzing the correlations between indicators and lower urinary tract dysfunction labels. Subsequently, the stability of diagnostic models was evaluated by five-fold cross-validation based on training data, while the performance was compared on test dataset. Results: UDS data from 134 female patients with a median age of 51 years (range, 27–78 years) were selected for our study.Among them, 66 patients suffered BOO and the remaining were normal. Applying the 5-fold cross-validation method, the model with the best performance achieved an area under the receiver operating characteristic curve (AUC) value of 0.949±0.060 using 9 UDS input features. The accuracy, sensitivity, and specificity for BOO diagnosis model in the testing process are 94.4%, 100%, and 89.3%, respectively. Conclusions The 9 significant indicators in UDS were employed to construct a diagnostic model of female BOO based on machine learning algorithm, which performs preferable classification accuracy and stability.