Objective: To analyze the characteristics and trends of drowning mortality among Chinese residents from 2010 to 2021, so as to provide a basis for developing targeted prevention strategies and reducing the burden of drowning deaths. Methods: Data on drowning mortality among Chinese residents from 2010 to 2021 were collected from the China Cause of Death Surveillance Dataset (2010-2021). The crude mortality was calculated and then standardized using the data from the Sixth National Population Census in 2010. The characteristics of drowning mortality were analyzed by genders, regions, and ages. The average annual percent change (AAPC) was employed to assess the trend in drowning mortality. Results: From 2010 to 2021, the overall crude drowning mortality among Chinese residents was 3.53/100 000, with a standardized mortality of 3.34/100 000, both showed decreasing trends (AAPC=-2.438% and -3.739%, both P<0.05). The crude and standardized mortality were higher in males than in females (4.55/100 000 vs. 2.47/100 000, 4.43/100 000 vs. 2.16/100 000, both P<0.05). Both the crude drowning mortality (AAPC=-2.974% and -1.337%) and standardized drowning mortality (AAPC=-3.806% and -3.599%) among males and females showed decreasing trends, respectively (all P<0.05). The crude and standardized drowning mortality were higher in rural residents than in urban residents (4.13/100 000 vs. 2.35/100 000, 3.86/100 000 vs. 2.27/100 000, both P<0.05). Both the crude and standardized drowning mortality in rural residents showed decreasing trends (AAPC=-3.343% and -4.515%, both P<0.05), whereas no statistically significant trends were observed in urban residents (both P>0.05). Both the crude and standardized drowning mortality were higher in western residents than in eastern residents and central residents (4.30/100 000 vs. 2.89/100 000 and 3.66/100 000, 4.14/100 000 vs. 2.64/100 000 and 3.49/100 000, all P<0.05). The standardized mortality showed decreasing trends in eastern, central and western residents (AAPC=-3.237%, -2.344%, and -5.467%, all P<0.05). The groups aged ≥65 years and 1-<5 years experienced relatively high crude drowning mortality of 8.81/105 and 7.38/105, respectively. Decreasing trends were observed in groups aged <1 year, 1-<5 years, and 5-<15 years (AAPC=-14.126%, -11.452%, and -7.443%, all P<0.05). In contrast, no statistically significant trends were observed in the other age groups (all P>0.05). Conclusions The overall drowning mortality rate among Chinese residents showed a declining trend from 2010 to 2021. However, the risks of drowning mortality remained relatively high among males, rural residents, residents in the western region, children, and the elderly.

Objective:To discuss the effect of zanubrutinib(BGB-3111)combined with bortezomib(Btz)on the apoptosis of the human multiple myeloma(MM)cells,and to clarify its possible mechanism.Methods:The human MM cell lines U266,PS-R,RPMI8226,KMS28-PE,KMS28-BM,and H929 were cultured in vitro.Western blotting method was used to detect the expression level of Bruton's tyrosine kinase(BTK)protein in various cells;cell counting kit-8(CCK-8)method was used to detect the survival rates of the RPMI8226,U266,and KMS28-BM cells after treated with 0,10,20,30,40,and 50 μmol·L?1 BGB-3111.The RPMI8226,U266,and KMS28-BM cells at the logarithmic growth phase were selected and divided into control group,BGB-3111 group,Btz group,and BGB-3111+Btz group.Flow cytometry was used to detect the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of myeloid cell leukemia 1(MCL-1),B-cell lymphoma-2(Bcl-2),Bcl-2-interacting mediator of cell death(Bim),phosphorylated Bim(p-Bim),P65,phosphorylated P65(p-P65),tumor necrosis factor receptor-associated factor(TRAF)2,and tumor necrosis factor alpha-induced protein 3(A20)in different kinds of cells.The U266 cells were divided into A20 overexpression group(A20-OE group)and empty vector control group(EV group).Each group was further divided into control group,BGB-3111 group,Btz group,and BGB-3111+Btz group.The corresponding plasmids were transfected;Western blotting method was used to detect the transfection efficiency of the cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups after over-expression of A20.Results:The Western blotting results showed that compared with KMS28-BM cells,the expression levels of BTK protein in the U266,RPMI8226,and H929 cells were significantly increased(P<0.05 or P<0.01).The CCK-8 results showed that compared with 0 μmol·L?1 BGB-3111 group,the survival rates of the RPMI8226 and U266 cells in 10,20,30,40,and 50 μmol·L?1 BGB-3111 groups were significantly decreased(P<0.05 or P<0.01),and the survival rates of the KMS28-BM cells in 20,30,40,and 50 μmol·L?1 BGB-3111 groups were significantly decreased(P<0.05).Compared with RPMI8226 and U266 cells,the survival rates of the KMS28-BM cells in 20,30,and 40 μmol·L?1 BGB-3111 groups were significantly increased(P<0.05).Therefore,10 μmol·L?1 BGB-3111 was selected for subsequent experiments.The flow cytometry results showed that compared with control group,the apoptotic rates of the RPMI8226 and U266 cells in BGB-3111 group,Btz group,and BGB-3111+Btz group were significantly increased(P<0.05 or P<0.01);compared with BGB-3111 group and Btz group,the apoptotic rates of the RPMI8226 and U266 cells in BGB-3111+Btz group were significantly increased(P<0.01);compared with control group,the apoptotic rates of the KMS28-BM cells in Btz group and BGB-3111+Btz group were significantly increased(P<0.01);compared with BGB-3111 group,the apoptotic rate of the KMS28-BM cells in BGB-3111+Btz group was significantly increased(P<0.01);compared with EV group,the apoptotic rates of the cells in A20-OE group in Btz group and BGB-3111+Btz group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of Bim protein in the RPMI8226 and U266 cells in BGB-3111 group,Btz group,and BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of MCL-1,p-Bim,and Bcl-2 proteins in the RPMI8226 and U266 cells in Btz group and BGB-3111+Btz group were significantly decreased(P<0.05);compared with BGB-3111 group and Btz group,the expression levels of Bim protein in the RPMI8226 and U266 cells in BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of MCL-1,p-Bim,and Bcl-2 proteins were significantly decreased(P<0.05).Compared with control group,the expression levels of p-P65 protein in the RPMI8226 and U266 cells in Btz group and BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of TRAF2 and A20 proteins were significantly decreased(P<0.05);compared with BGB-3111 group and Btz group,the expression levels of p-P65 protein in the RPMI8226 and U266 cells in BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of TRAF2 and A20 proteins were significantly decreased(P<0.05).The flow cytometry results showed that compared with EV group,the expression level of A20 protein in A20-OE group cells was significantly increased(P<0.01).Conclusion:BGB-3111 induces apoptosis in the MM cells by inhibiting BTK activity and enhances the pro-apoptotic effect of Btz.Over-expression of A20 increases the sensitivity of the MM cells to the combined treatment.The antitumor effect may be related to the inhibition of the nuclear factor kappa B(NF-κB)signaling pathway.

Objective:To explore the perioperative safety and postoperative efficacy of prophylactic jejunal nutrition tube placement during early gastric body cancer pylorus-preserving gastrectomy (PPG).Methods:The clinical data of 29 gastric cancer patients treated by Beijing Friendship Hospital, Capital Medical University from January 2018 to December 2024 were retrospectively analyzed. There were 17 males (58.6%) and 12 females (41.4%), aged from 43 to 74 years, with an average age of (58.9 ± 8.3) years, and an average body mass index (BMI) of (24.3 ± 3.0) kg/m 2. According to the type of catheterization, all cases were divided into jejunal nutrition tube group ( n=12) and gastric tube group( n=17). The main outcome was the incidence of delayed gastric emptying within one month after surgery in both groups. Statistical analysis was conducted using SPSS26.0 software. Results:Patients in the jejunal feeding tube group resumed oral liquid intake, soft diet and regular diet significantly earlier postoperatively compared to those in the gastric tube group, with statistically significant differences ( P<0.05). Conversely, the time to removal of the tube was significantly earlier in the gastric tube group than in the jejunal feeding tube group ( P<0.05). However, the proportion of patients requiring reinsertion of a gastric or jejunal feeding tube postoperatively was significantly higher in the gastric tube group (7 cases) compared to the jejunal feeding tube group (0 case) ( P<0.05). In the jejunal feeding tube group, there were 4 cases occurred DGE, in the gastric tube group, there were 8 cases occurred DGE. There were no statistically significant differences between the two groups in either the overall incidence of DGE or the distribution of DGE severity grades. On postoperative 7th day , the Gastric Outlet Obstruction Scoring System (GOOSS) grade was significantly better in the jejunal feeding tube group than in the gastric tube group ( P<0.05), and all patients in the jejunal feeding tube group had resumed liquid intake, compared to only 58.8% in the gastric tube group. Conclusions:Compared with gastric tube placement, intraoperative prophylactic jejunal feeding tube placement for PPG has significant advantages in perioperative safety and postoperative recovery, but large-sample prospective studies are still needed for further verification.

Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.

Objective To develop a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for simultaneous determination of five flavonoids in Ganmao'an granules(GMA).Methods Chromatographic separation was achieved on a Kromasil C18 Column(150 mm×4.6 mm,5 μm,100 ?),which was eluted with methanol(A)-0.1％formic acid(B)at the flow rate of 1.0 ml/min.The gradient condition was as follows:0-20 min,35％A,and 20-40 min,45％A.The column temperature was 25 ℃.Analytes were detected using a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source in the negative ion scanning.The multiple reaction monitoring mode was used for qualitative analysis.For each flavonoid,two precursor ion/product ion transitions were chosen:lutin m/z 609.1→300.1,hyperin and isoquercitrin m/z 463.0→300.1,quercetin m/z 301.0→151.0,luteolin m/z 285.0→132.9.Results Five flavonoids showed the good relationships within their own concentration ranges(correlation coefficient r>0.999 1),whose average recoveries were in the range of 100.63％-102.81％with RSDs of 0.67％-2.07％.The content results of rutin,hyperoside,isoquercetin,quercetin,and luteolin in 10 batches of GMA were 32.23-479.83,0.291-1.825,11.44-20.54,6.32-18.41,3.46-6.51 μg/g,respectively.Conclusion The results indicated that the developed method was sensitive,accurate and could provide excellent specificity for simultaneous determination of five flavonoids in GMA.

Objective:To prepare advanced platelet-rich fibrin (A-PRF)/chitosan thermosensitive hydrogel (hereinafter referred to as composite hydrogel) and explore the effects of composite hydrogel on full-thickness skin defect wound healing in diabetic rats.Methods:This study was an experimental study. The composite hydrogel with porous mesh structure and thermosensitive characteristics was successfully prepared, containing A-PRF with mass concentrations of 10, 15, 20, 50, and 100 g/L. Diabetic model was successfully established in male Sprague-Dawley rats aged 6-8 weeks by intraperitoneal injection of streptozotocin, and 4 full-thickness skin defect wounds were established on the back of each rat (finally the model was successfully established in 36 rats). Three wounds of each rat were divided into blank group (no drug intervention), positive control group (dropping recombinant human granulocyte-macrophage stimulating factor gel), and chitosan hydrogel group (dropping chitosan hydrogel solution). Thirty rats were collected, and the remaining one wound of each rat (totally 30 wounds) was divided into 10, 15, 20, 50, and 100 g/L composite hydrogel groups, with 6 wounds in each group, which were dropped with composite hydrogel solution containing 10, 15, 20, 50, and 100 g/L A-PRF, respectively. Taking the remaining six rats, the remaining one wound from each rat was dropped with composite hydrogel solution containing 100 g/L A-PRF. On 14 d after injury, 6 rats with one wound dropped with composite hydrogel containing 100 g/L A-PRF were selected for hematoxylin-eosin (HE) staining to observe the inflammation, hemorrhage, or necrosis of the heart, liver, spleen, lung, and kidney. On 10 d after injury, 6 rats with one wound dropped with composite hydrogel containing 15 g/L A-PRF were selected to observe the blood perfusion of wounds in the four groups (with sample size of 6). On 7 and 14 d after injury, the wound healing rates in the eight groups were calculated. On 14 d after injury, the wound tissue in the eight groups was taken for HE and Masson staining to observe the formation of new epithelium and collagen formation, respectively; the positive expressions of CD31 and vascular endothelial growth factor A (VEGFA) were detected by immunohistochemistry, and the percentages of positive areas were calculated; the protein expressions of CD31 and VEGFA were detected by Western blotting; the mRNA expressions of CD31 and VEGFA were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction method (with all sample sizes of 4).Results:On 14 d after injury, no obvious inflammation, hemorrhage, or necrosis was observed in the heart, liver, spleen, lung, and kidney in the 6 rats. On 10 d after injury, the blood perfusion volume of wound in 15 g/L composite hydrogel group was significantly more than that in blank group, positive control group, and chitosan hydrogel group, respectively (with P values all <0.05). On 7 and 14 d after injury, the wound healing rates of blank group were (26.0±8.9)% and (75.0±1.8)%, which were significantly lower than those of positive control group, chitosan hydrogel group, and 10, 15, 20, 50, and 100 g/L composite hydrogel groups, respectively ((45.8±3.2)%, (49.8±3.7)%, (51.2±2.9)%, (68.5±2.4)%, (68.8±1.5)%, (72.7±2.1)%, (75.0±3.7)% and (79.1±1.9)%, (77.2±1.7)%, (82.3±1.3)%, (89.6±1.9)%, (89.8±1.3)%, (87.3±1.1)%, (87.9±1.3)%), P<0.05; the wound healing rates of positive control group, chitosan hydrogel group, and 10 g/L composite hydrogel group were significantly lower than those of 15, 20, 50, and 100 g/L composite hydrogel groups ( P<0.05). On 14 d after injury, the wound epithelialization degrees of 15, 20, 50, and 100 g/L composite hydrogel groups were higher than those of the other 4 groups, the new microvascular situation was better, and the collagen was more abundant and arranged more neatly. On 14 d after injury, the percentages of CD31 and VEGFA positive areas in wounds in positive control group and the percentage of VEGFA positive area in wounds in chitosan hydrogel group were significantly higher than those in blank group ( P<0.05), the percentage of VEGFA positive area in wounds in 10 g/L composite hydrogel group was significantly higher than that in blank group, chitosan hydrogel group, and positive control group (with P values all <0.05), and the percentages of CD31 and VEGFA positive areas in wounds in 15, 20, 50, and 100 g/L composite hydrogel groups were significantly higher than those in blank group, positive control group, chitosan hydrogel group, and 10 g/L composite hydrogel group ( P<0.05). On 14 d after injury, the protein and mRNA expressions of CD31 and VEGFA in wound tissue in chitosan hydrogel group, positive control group, and 10 g/L composite hydrogel group were significantly higher than those in blank group ( P<0.05); the protein expression of VEGFA in wound tissue in 10 g/L composite hydrogel group was significantly higher than that in positive control group ( P<0.05), and the mRNA expressions of CD31 and VEGFA in wound tissue in 10 g/L composite hydrogel group were significantly higher than those in positive control group and chitosan hydrogel group ( P<0.05); the protein and mRNA expressions of CD31 and VEGFA in wound tissue in 15, 20, 50, and 100 g/L composite hydrogel groups were significantly higher than those in blank group, positive control group, chitosan hydrogel group, and 10 g/L composite hydrogel group ( P<0.05); the mRNA expressions of CD31 and VEGFA in wound tissue in chitosan hydrogel group were significantly lower than those in positive control group ( P<0.05). Conclusions:The composite hydrogel has high biological safety, can improve wound blood perfusion, effectively promote the formation of blood vessels and collagen in wound tissue, thus promoting the wound healing of full-thickness skin defects in diabetic rats. 15 g/L is the optimal mass concentration of A-PRF in composite hydrogel.

Objective To observe the clinical efficacy of intravenous transplantation of human umbilical cord blood mononuclear cells(hUCB-MNC)in the treatment of patients with mild-to-moderate Alzheimer disease(AD).Methods Fifty patients with mild-to-moderate AD were randomly divided into treatment group and control group,with 25 cases in each group.The treatment group received intravenous infusion of hUCB-MNC,while the control group was given donepezil hydrochloride by oral administration.The course of treatment was 12 weeks in both groups.We evaluated 1H-proton magnetic resonance spectroscopy(1H-MRS)parameters[N-acetylaspartate/creatinine(NAA/Cr),choline/cre-atinine(Cho/Cr),inositol/creatinine(mI/Cr),and N-acetylaspartate/inositol(NAA/mI)ratios],urinary AD7c-NTP level,and Montreal Cognitive Assessment(MoCA)score in both groups before and after treatment.Results After treat-ment,the treatment group showed significant increases in the total MoCA score and the score of each cognitive domain;and the treatment group had significant greater improvements in memory,visuospatial and executive function,attention,and orientation than the control group(all P<0.05).After treatment,the treatment group showed significantly increased NAA/Cr,Cho/Cr,and NAA/mI ratios and a significantly decreased mI/Cr ratio;and the improvements in NAA/Cr,Cho/Cr,NAA/mI,and mI/Cr were significantly greater in the treatment group than in the control group(all P<0.05).The uri-nary AD7c-NTP level in the treatment group was significantly reduced after treatment,and the improvement was signifi-cantly better compared with the control group(both P<0.05).Conclusion Intravenous transplantation of hUCB-MNC can significantly improve memory,visuospatial and executive function,and other cognitive domains as well as brain me-tabolism and neuronal damage in patients with mild-to-moderate AD.1H-MRS and urinary AD7c-NTP evaluations can pro-vide new ideas for the clinical treatment of AD.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore potential genes associated with the pathogenesis of hypospadias using weighted Gene co-expression network analysis(WGCNA).Methods The WGCNA algorithm was used to process the hypospadias-related dataset GSE35034,and then a gene co-expression weight network was constructed to screen the modules with the highest correlation with hypospadias,and the genes in the modules were enriched and detected by gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG).Differential analysis was also performed to screen out differential genes.The differential genes were imported into the String database.Using Cytoscape software,the hub genes in the network were identified.The results screened by the above three methods were combined and analyzed,and the core genes in the intersection set were screened.Using the external dataset GSE121712,the core genes were verified by mRNA expression changes and subject work characterization receiver operating characteristic(ROC)curve diagnosis.Results Fifteen co-expression modules were obtained based on the WGCNA method.Ninety-three common differential genes meeting the conditions were obtained by differential analysis.Ten core genes were finally obtained by Cytoscape software analysis.Finally MEbrown module,differential genes and the 10 core genes yielded a total of 2 intersecting genes:FBXL16 and SYNDIG1.ROC curves verified that the intersecting genes were differentially expressed in patients with hypospadias versus normal subjects.Conclusion In this study,two key genes with significant correlation with hypospadias were obtained by WGCNA,which may be used for the early diagnosis and treatment of hypospadias after further study.

Drimane-type sesquiterpenoids are widely distributed in fungi. From the ethyl acetate extract of the earwig-derived Aspergillus sp. NF2396, seven new drimane-type sesquiterpenoids, named drimanenoids A-G (1-7), were isolated. Their structures were elucidated by diverse spectroscopic analysis including high-resolution ESI-MS, one- and two-dimensional NMR spectroscopy. Drimanenoids A-F (1-6) are new members of drimane-type sesquiterpenoid esterified with unsaturated fatty acid side chain at C-6. Drimanenoids C (3), D (4) and F (6) showed antibacterial activity against five types of bacteria with different inhibition diameters. Drimanenoid D (4) exhibited moderate cytotoxicity against human myelogenous leukemia cell line K562 with an IC₅₀ value of 12.88 ± 0.11 μmol·L^-1.
Humans ; Polycyclic Sesquiterpenes ; Sesquiterpenes/chemistry* ; Aspergillus/chemistry* ; Magnetic Resonance Spectroscopy ; Molecular Structure