Objective To improve the underwater technique during the start phase of breaststroke swimmers through swimming flume training and assess its effectiveness in enhancing competitive performance.Methods The participants were 14 male swimmers in the short-distance Level 4 category from the Shanghai Swimming Team,and they were randomly divided into the experimental group(n=7)and control group(n=7).The experimental group underwent swimming flume start training,while the control group underwent regular pool start training,and both groups received the training twice a week for 16 weeks.Before and after the 16-week training,a 15-m breaststroke start test was conducted.Repeated measures analysis of variance and paired t-tests were used to compare the changes in kinematic parameters(time,speed,and entry angle)between and within groups.Results After 16 weeks of specialized training,the 15-m performance at the start for the experimental group and control group(F(1,12)=6.52,P＜0.05,η2=0.39)showed an interaction,with the experimental group performing better after training compared to the control group before training(P＜0.05).In the experimental group,the duration of the pull-out phase(F(1,12)=10.28,P＜0.01,η2=0.46)and the second sliding phase(F(1,12)=4.81,P＜0.05,η2=0.22)was improved;the distance of the pull-out phase(F(1,12)=4.71,P＜0.05,η2=0.21)and the second sliding phase(F(1,12)=4.90,P＜0.05,η2=0.21)was improved;the speed of the pull-out phase(F(1,12)=4.77,P＜0.05,72=0.20)was significantl improved.The within-group statistics showed that the experimental group significantly improved their exit speed(P＜0.05).The hand entry angle was optimized(P＜0.05),while changes in other joint angles were not significant.Conclusions Swimming flume training reduced the time spent in the pull-out and second gliding phases during the breaststroke start,effectively preventing the speed loss during underwater gliding.This provides an experimental evidence for enhancing start performance and optimizing training method for breaststroke swimmers.

Objective:To investigate the effects of metformin on esophageal squamous cell carcinoma cell growth, migration and angiogenesis by regulating the expression of ALKBH3.Methods:Human esophageal cancer TE-1 cells were treated with different concentrations (0, 0.5, 1.0, 2.0, 4.0, 8.0 mmol/L) of metformin, and they were divided into a blank control group, low- (0.5 mmol/L), medium- (1.0 mmol/L), and high- (2.0 mmol/L) concentration metformin groups, a metformin (2.0 mmol/L) +pcDNA-NC group, and a metformin (2.0 mmol/L) +pcDNA-ALKBH3 group. The cell viability was determined by the CCK-8 method. The cell proliferation ability was detected by the clone formation assay. The cell migration and invasion abilities were examined by the Transwell assay. The cell apoptosis was detected by flow cytometry. The tube formation ability of cells was detected by the angiogenesis assay. A xenograft tumor model was constructed using 4- to 6-week-old male BALB/c thymus-less nude mice, which were divided into a model control group, a metformin group, a metformin+pcDNA-NC group, and a metformin+pcDNA-ALKBH3 group using a random number table method, and with six in each group. And the volume and weight of the tumor were measured. The protein expression levels of apoptosis-related proteins Bcl-2, Bax, ALKBH3 and vascular endothelial growth factor A (VEGF-A) were detected by Western blotting. The expression of CD31 protein was detected by immunohistochemistry.Results:After treating TE-1 cells with 0, 0.5, 1.0, 2.0, 4.0, and 8.0 mmol/L metformin for 48 hours, the cell viability was (100.00±0.00) %, (90.31±5.23) %, (81.25±8.65) %, (63.52±6.80) %, (54.64±5.35) %, and (31.48±4.21) %, respectively, with a statistically significant difference ( F=98.11, P<0.001). There were statistically significant differences in cell viability between 0.5, 1.0, 2.0, 4.0, 8.0 mmol/L and 0 mmol/L (all P<0.05). The IC 50 of metformin for TE-1 cells was 4.46 mmol/L. The numbers of colony formations of TE-1 cells in the blank control group, low-, medium-, and high-concentration metformin groups, metformin+pcDNA-NC group, and metformin+pcDNA-ALKBH3 group were 153.15±13.55, 134.80±11.62, 116.24±10.43, 93.17±8.85, 89.39±8.46, 110.26±7.21, respectively, with a statistically significant difference ( F=34.28, P<0.001); the numbers of colony formations of TE-1 cells in the metformin groups at different concentrations decreased significantly with the increase in metformin concentration (both P<0.05); compared with the metformin+pcDNA-NC group, the number of colony formations of cells in the metformin+pcDNA-ALKBH3 group increased ( P<0.05). The numbers of migration of TE-1 cells of 6 groups were 152.13±13.40, 133.85±10.72, 115.28±8.64, 91.16±7.89, 85.39±7.23, 116.85±8.36, the numbers of invasion were 135.22±10.77, 112.07±9.53, 86.30±7.45, 69.53±6.74, 65.81±5.65, 79.80±6.32, respectively, with statistically significant differences ( F=41.35, P<0.001; F=69.06, P<0.001); the numbers of migrated and invaded cells in the metformin groups at different concentrations decreased significantly with the increase in metformin concentration (all P<0.05); compared with the metformin+pcDNA-NC group, the numbers of migrated and invaded cells in the metformin+pcDNA-ALKBH3 group increased significantly (both P<0.05). The apoptosis rates of TE-1 cells in 6 groups were (3.22±1.13) %, (13.82±1.90) %, (22.67±2.53) %, (29.18±3.24) %, (26.84±2.75) %, and (16.36±1.63) %, respectively, with a statistically significant difference ( F=103.66, P<0.001); the apoptosis rates of cells in the metformin groups at different concentrations gradually increased with the increase in metformin concentration (both P<0.05); compared with the metformin+pcDNA-NC group, the apoptosis rate of cells in the metformin+pcDNA-ALKBH3 group was relatively lower ( P<0.05). The tubular structure of cells in blank control group was intact, and there were different degrees of damage to the tubular structure of cells in the low-, medium-, high- concentration metformin groups, the degree of damage to the tubular structure of cells in the metformin+pcDNA-ALKBH3 group was reduced. The numbers of cellular tubular structures of TE-1 cells in the 6 groups were 38.35±3.20, 27.15±2.64, 15.92±3.14, 7.39±1.50, 8.61±1.37, and 29.33±4.20, respectively, with a statistically significant difference ( F=113.92, P<0.001); the number of cellular tubular structures in the low-, medium-, and high- concentration metformin groups gradually decreased (both P<0.05); the number of cellular tubular structures in the metformin+pcDNA-ALKBH3 group was more than that in the metformin+pcDNA-NC group ( P<0.05). There were statistically significant differences in the protein expressions of Bcl-2, Bax, ALKBH3, and VEGF-A in TE-1 cells among 6 groups ( F=56.36, P<0.001; F=57.26, P<0.001; F=159.30, P<0.001; F=132.89, P<0.001); compared with the blank control group, the protein expressions of Bcl-2, ALKBH3, and VEGF-A in the metformin groups at different concentrations decreased, while the protein expression of Bax increased (all P<0.05); compared with the metformin+pcDNA-NC group, the protein expressions of Bcl-2, ALKBH3, and VEGF-A in the metformin+pcDNA-ALKBH3 group increased, and the expression level of Bax decreased (all P<0.05). The weights of tumors in the model control group, metformin group, metformin+pcDNA-NC group, and metformin+pcDNA-ALKBH3 group were (1.16±0.12), (0.46±0.05), (0.50±0.06), (1.19±0.14) g, the volumes of tumors were (878.36±108.93), (413.59±50.23), (439.78±51.39), (793.75±96.98) mm 3, with statistically significant differences ( F=96.61, P<0.001; F=51.90, P<0.001); the weight of tumors were lower and the volume of tumors were smaller in the metformin group than those in the model control group (both P<0.05), the weight of tumors were higher and the volume of tumors were bigger in the metformin+pcDNA-ALKBH3 group than those in the metformin group and the metformin+pcDNA-NC group (all P<0.05). CD31 was mainly distributed in the cytoplasm and cell membrane of tumor cells. There were statistically significant differences in the positive rates of CD31 and the protein expression levels of VEGF-A in transplanted tumor tissues among 4 groups ( F=7.12, P=0.002; F=48.81, P<0.001); the positive rate of CD31 and the protein expression level of VEGF-A in the metformin group were lower than those in the model control group; the positive rate of CD31 and the protein expression level of VEGF-A in the metformin+pcDNA-ALKBH3 group were higher than those in the metformin group and the metformin+pcDNA-NC group (all P<0.05) . Conclusions:Metformin may inhibit the proliferation, migration, and tumor angiogenesis of esophageal squamous cell carcinoma by reducing ALKBH3 expression.

Objective:The influencing factors of intraoperative hypoxemia in patients with benign central airway stenosis were investigated by machine learning algorithm, and the prediction model of hypoxemia was constructed and verified.Methods:A case-control study was used in this study. The clinical data of 650 patients with benign central airway stenosis who who received surgical treatment in the First Affiliated Hospital of PLA Naval Medical University from June 2022 to April 2024 were retrospectively analyzed. And they were divided into a training set ( n=455) and a test set ( n=195) according to 7:3. The training set was used for establishing Logistic regression model and conducting internal verification, and the test set was used for external verification. The least absolute shrinkage and selection operator (LASSO) regression and Boruta algorithm were used to select the factors affecting intraoperative hypoxemia in patients with benign central airway stenosis. A Logistic regression prediction model was constructed, and the model was evaluated using area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA) and calibration curve. Shapley additive interpretation (SHAP) were used to analyze the importance of influencing factors. Results:Among 650 patients, 279 were males and 371 were females, aged (37.86 ± 8.82) years. Nine feature variables were screened by LASSO regression, while 7 feature variables were screened by Boruta algorithm, the intersection of the two was operation time, complications, degree of airway stenosis, thermal ablation therapy, balloon dilation, and airway stent, respectively, based on this, a logistic regression prediction model was constructed.The AUC values of the training set, validation set and test set of the model were 0.928 (95% CI 0.903-0.954), 0.922 (95% CI 0.843-0.995) and 0.919 (95% CI 0.872-0.965), respectively. The calibration curve showed that the predicted results of the model were in good agreement with the actual results, and the DCA curve showed that the model had clinical application value. SHAP analysis showed that the importance of variables affecting intraoperative hypoxemia in benign central airway stenosis patients was ranked as operation time, thermal ablation therapy, degree of airway stenosis, comorbidification, balloon dilation, and airway stent. Conclusions:The Logistic regression prediction model of intraoperative hypoxemia built based on machine learning algorithm has good prediction efficiency, which is helpful to early identification of risk groups and prevention of hypoxemia.

Objective To improve the underwater technique during the start phase of breaststroke swimmers through swimming flume training and assess its effectiveness in enhancing competitive performance.Methods The participants were 14 male swimmers in the short-distance Level 4 category from the Shanghai Swimming Team,and they were randomly divided into the experimental group(n=7)and control group(n=7).The experimental group underwent swimming flume start training,while the control group underwent regular pool start training,and both groups received the training twice a week for 16 weeks.Before and after the 16-week training,a 15-m breaststroke start test was conducted.Repeated measures analysis of variance and paired t-tests were used to compare the changes in kinematic parameters(time,speed,and entry angle)between and within groups.Results After 16 weeks of specialized training,the 15-m performance at the start for the experimental group and control group(F(1,12)=6.52,P＜0.05,η2=0.39)showed an interaction,with the experimental group performing better after training compared to the control group before training(P＜0.05).In the experimental group,the duration of the pull-out phase(F(1,12)=10.28,P＜0.01,η2=0.46)and the second sliding phase(F(1,12)=4.81,P＜0.05,η2=0.22)was improved;the distance of the pull-out phase(F(1,12)=4.71,P＜0.05,η2=0.21)and the second sliding phase(F(1,12)=4.90,P＜0.05,η2=0.21)was improved;the speed of the pull-out phase(F(1,12)=4.77,P＜0.05,72=0.20)was significantl improved.The within-group statistics showed that the experimental group significantly improved their exit speed(P＜0.05).The hand entry angle was optimized(P＜0.05),while changes in other joint angles were not significant.Conclusions Swimming flume training reduced the time spent in the pull-out and second gliding phases during the breaststroke start,effectively preventing the speed loss during underwater gliding.This provides an experimental evidence for enhancing start performance and optimizing training method for breaststroke swimmers.

Objective:The influencing factors of intraoperative hypoxemia in patients with benign central airway stenosis were investigated by machine learning algorithm, and the prediction model of hypoxemia was constructed and verified.Methods:A case-control study was used in this study. The clinical data of 650 patients with benign central airway stenosis who who received surgical treatment in the First Affiliated Hospital of PLA Naval Medical University from June 2022 to April 2024 were retrospectively analyzed. And they were divided into a training set ( n=455) and a test set ( n=195) according to 7:3. The training set was used for establishing Logistic regression model and conducting internal verification, and the test set was used for external verification. The least absolute shrinkage and selection operator (LASSO) regression and Boruta algorithm were used to select the factors affecting intraoperative hypoxemia in patients with benign central airway stenosis. A Logistic regression prediction model was constructed, and the model was evaluated using area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA) and calibration curve. Shapley additive interpretation (SHAP) were used to analyze the importance of influencing factors. Results:Among 650 patients, 279 were males and 371 were females, aged (37.86 ± 8.82) years. Nine feature variables were screened by LASSO regression, while 7 feature variables were screened by Boruta algorithm, the intersection of the two was operation time, complications, degree of airway stenosis, thermal ablation therapy, balloon dilation, and airway stent, respectively, based on this, a logistic regression prediction model was constructed.The AUC values of the training set, validation set and test set of the model were 0.928 (95% CI 0.903-0.954), 0.922 (95% CI 0.843-0.995) and 0.919 (95% CI 0.872-0.965), respectively. The calibration curve showed that the predicted results of the model were in good agreement with the actual results, and the DCA curve showed that the model had clinical application value. SHAP analysis showed that the importance of variables affecting intraoperative hypoxemia in benign central airway stenosis patients was ranked as operation time, thermal ablation therapy, degree of airway stenosis, comorbidification, balloon dilation, and airway stent. Conclusions:The Logistic regression prediction model of intraoperative hypoxemia built based on machine learning algorithm has good prediction efficiency, which is helpful to early identification of risk groups and prevention of hypoxemia.

A derivatizaton method combined with gas chromatography-mass spectrometry(GC-MS)was established for detection of isobutyl chloroformate(IBCF)residue in active pharmaceutical ingredient of agatroban.The extraction and derivatization reagents,derivatization time,qualitative and quantitative ions were selected and optimized,respectively.The possible mechanism of derivatization and characteristic fragment ions fragmentation were speculated.The agatroban samples were dissolved and extracted by methanol,and the residual IBCF was derived with methanol to generate methyl isobutyl carbonate(MIBCB).After 24 h static derivatization at room temperature,IBCF was completely transformed into MIBCB,which could be used to indirectly detect IBCF accurately.The results showed that the linearity of this method was good in the range of 25-500 ng/mL(R2=0.9999).The limit of detection(LOD,S/N=3)was 0.75 μg/g,and the limit of quantification(LOQ,S/N=10)was 2.50 μg/g.Good recoveries(95.2%-97.8%)and relative standard deviations(RSDs)less than 3.1%(n=6)were obtained from agatroban samples at three spiked levels of IBCF(2.50,25.00,50.00 μg/g),which showed good accuracy of this method.Good precision of detection results was obtained by different laboratory technicians at different times,the mean value of spiked sample solution(25.00 μg/g)was 24.28 μg/g,and the RSD was 2.1%(n=12).The durability was good,minor changes of detection conditions had little effect on the results.Under the original condition and conditions with initial column temperature±5℃,heating rate±2℃/min,column flow rate±0.1 mL/min,the IBCF content of spiked sample solution(25.00 μg/g)was detected,the mean value of detection results was 24.16 μg/g,and the RSD was 2.2%(n=7).Eight batches of agatroban samples from two manufacturers were detected using the established method,and the results showed that no IBCF residue was detected in any of these samples.The agatroban samples could be dissolved by methanol,and then the IBCF residue could be simultaneously extracted and derived with methanol as well.This detection method had the advantages of simple operation,high sensitivity,low matrix effect and accurate quantification,which provided a new effective method for detection of IBCF residue in agatroban.

In this study, we have firstly investigated the feasibility of rhamnolipids as targeting ligands to develop drug delivery systems for active targeting of pancreatic cancer. Rhamnolipid-modified liposomes (RhaL-Lip) were prepared by a thin film hydration method, and were evaluated preliminarily for RhaL-Lip physicochemical properties, in vitro release characteristics, ex/in vivo targeting, and in vitro pharmacodynamics. RhaL-Lip exhibited excellent targeting ability of human pancreatic cancer (BxPC-3) cells and enhanced anti-tumor effects. On this basis, the natural structural analogue of rhamnolipid, Polyphyllin VII (PPVII), as the targeting material and active ingredient, we explored the targeting and anti-tumor activity of Polyphyllin VII modified liposomes (PPVII-Lip). The results showed that PPVII-Lip has a homogeneous particle size and has a more robust targeting ability for solid tumor in vivo, which can achieve more enrichment at the tumor site. Compared with gemcitabine, the first-line chemotherapy drug for pancreatic cancer, PPVII-Lip showed a stronger inhibitory effect. In conclusion, this targeted drug delivery strategy is expected to provide beneficial ideas for drug delivery studies in targeted therapy for pancreatic cancer. Animal experiments were conducted with approval from the Animal Ethics Committee of southwest university (approval number: IACUC-20210130-2).

Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L^-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.

A patient was admitted to hospital due to umbilical pain.Gram-staining presented short,positive coc-cobacillus in the purulent secretions from the umbilical cord of the patient.Meanwhile,matrix-assisted laser desorp-tion/ionization time-of-flight mass spectrometry(MALDI-TOF MS),16S rRNA detection,and in vitro antimicro-bial susceptibility testing were performed on the isolated strains.Corynebacterium tuberculostearicum was identified by Gram-staining,MALDI-TOF MS and 16S rRNA.Antimicrobial susceptibility testing results showed that the strain was sensitive to penicillin,ceftriaxone,cefepime,meropenem,vancomycin,daptomycin,linezolid,compound sulfamethoxazole,ampicillin,gentamicin and tetracycline.Smear of microorganisms is helpful for the identification of Corynebacterium tuberculostearicum morphology,and MALDI-TOF MS is necessary for rapid identification of strains.Antimicrobial susceptibility testing can also assist the empirical treatment for infection due to this strain.

One patient was admitted to a hospital due to"sepsis,chronic kidney disease,type 2 diabetes,shock,and cerebral infarction".Patient's blood specimen was taken for clinical examination.Aerobic and anaerobic culture results of catheter blood and venous blood were both positive.The pathogen was identified as Staphylococcus pas-teuri by VITEK MS,and the patient was diagnosed as catheter-related bloodstream infection caused by Staphylo-coccus pasteuri.Clinical empirical use of piperacillin for anti-infection treatment was ineffective,and vancomycin was eventually used for treatment based on in vitro antimicrobial susceptibility testing.Patient's condition improved after removing the venous catheter.There are currently no reported cases of Staphylococcus pasteuri in China.Ear-ly identification of pathogen and adjustment of treatment plans based on antimicrobial susceptibility testing results are crucial for effective treatment of this case.