Objective To assess the value of acute gastrointestinal injury(AGI)and intestinal fatty acid-binding protein(I-FABP)in the prognosis of liver cirrhotic patients with sepsis.Methods Clinical data of 84 liver cirrhosis patients with sepsis who were admitted to the intensive care unit(ICU)of a hospital from September 2020 to March 2023 were analyzed retrospectively,and 41 patients with decompensated liver cirrhosis during the same period were selected as the control group.Serum I-FABP level in patients was determined with enzyme-linked immunosorbent assay(ELISA).Scores of the model of end-stage liver disease(MELD)and sequential organ failure assessment(SOFA)were calculated.AGI was evaluated based on medical records.30-day and 90-day survival was observed.Correlation among variables was analyzed by Spearman correlation.Risk factors for death in patients with liver cir-rhosis and sepsis was determined by multivariate Cox regression analysis.The optimal cut-off value was determined by receiver operating characteristic(ROC)curve,and the diagnostic efficacy was compared through the area under the ROC curve(AUC).Results Both AGI grading and I-FABP level in liver cirrhosis patients with sepsis were higher than those in the control group(both P＜0.05).I-FABP level was correlated with procalcitonin(PCT),MELD,and SOFA scores in patients with liver cirrhosis and sepsis(all P＜0.05).AGI grading was positively cor-related with SOFA score(P=0.038).The 30-day and 90-day mortality of patients in the liver cirrhosis with sepsis group were 25.0％(n=21)and 35.7％(n=30),respectively.Multivariate Cox regression analysis showed that baseline I-FABP and SOFA scores were independently correlated with 30-day and 90-day survival,and the I-FABP quartile showed good prognostic differentiation efficacy.ROC curve showed that I-FABP could significantly improve the predictive effect of SOFA score on the prognosis of patients.Conclusion AGI grading and I-FABP level in liver cirrhosis patients with sepsis are elevated significantly.Serum I-FABP is associated with the prognosis of patient and can improve the predictive efficacy of SOFA score for survival.

Objective: Investigation on the quality control method of bacterial endotoxin in betahistine hydrochloride injection.
Methods: The method of bacterial endotoxin gel test of 23 batches of betahistine hydrochloride injection from 5 manufacturers was studied.
Results: The limit value of endotoxin in this product was 3 EU·mg^-1, which was suitable for the bacterial endotoxin test of China Pharmacopoeia 2020.
Conclusion: The quality of betahistine hydrochloride injection can be controlled by bacterial endotoxin test, and the limit of bacterial endotoxin can be set as follows: the content of endotoxin in every 1mg of betahistine hydrochloride should not exceed 3 EU.

Objective:We examined the levels of Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling in head and neck squamous cell carcinoma(HNSCC)and their influence on chemotherapy sensitization.Methods:Sixty patients with HNSCC who were treated at Tianjin Medical University Cancer Institute&Hospital,between January 2018 and December 2022,were included in the study.Levels of expressed JAK2,p-STAT3Y705,c-Myc,and Ki-67 in HNSCC tissues were evaluated using immunohistochemical staining,and correlation analysis was performed.The viability of UM-SCC1 cells treated with fedratinib,a JAK2 inhibitor,combined with cisplatin(DDP)and paclitaxel(PTX)was determined using the CCK8 assay.Western blot was performed to detect p-STAT3Y705 expression in tumor tissues and HNSCC cell lines.SCC15 and UM-SCC1 cell lines stably transfected with JAK2 or STAT3 vectors were constructed and verified.Cell activity and cell proliferation capacity were measured to evaluate the detrimental impact of STAT3 overexpression on chemotherapy with fedratinib using Western blot,CCK8,and plate cloning assays.Results:JAK2 expression in HNSCC positively correlated with p-STAT3Y705(r=0.43,P<0.000 1)and c-Myc(r=0.48,P<0.01)expression.High p-STAT3Y705 expression positively correlated with AJCC stage(P<0.000 1)and Ki-67 expression(P<0.05).High STAT3 and p-STAT3 levels were associated with poor prognosis in patients with HNSCC.In vitro,the JAK2 inhibitor fedratinib inhibited HNSCC cell proliferation and enhanced tumor cell sensitivity to DDP and PTX.JAK2 activation promotes STAT3 phosphorylation,and STAT3 overexpression reverses the effects of fedratinib on HNSCC sensitivity to chemotherapy.Conclusions:JAK2/STAT3 signaling is elev-ated in patients with HNSCC.Targeting the JAK2/STAT3 pathway is a potential method for increasing the sensitivity of HNSCC to chemotherapy.

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.

The distribution of Ixodes and Ana plasma carried by Ixodes ticks in Anhui Province was clarified as reference for prevention and control of anaplasmosis.In total,630 hard ticks were collected from Jinzhai County,Hanshan County,Jing-de County and Chaohu City in Anhui Province from April to August 2023.Ticks were identified by morphological analysis and 16S rRNA sequencing.Nested PCR with Anaplasma species-specific primers were used to detect 16S rRNA of Anaplasma spe-cies carried by ticks.A phylogenetic tree was constructed using MEGA11.0 software.Of the identified ticks,18.8％(18/96)were Rhipicephalus microplus and 81.2％(78/96)were Haemaphysalis longicorni in Jinzhai County of Anhui Province,all were H.longicorni in Hanshan County and Chaohu City,while the main species in Jingde County was R.microplus.The posi-tive rate of Anaplasma carried by H.longicornis was 30.9％(102/330),which included A.bovis at 1.8％(6/330),A.phagocytophilum at 21.8％(72/330)and uncultured Anaplasma species at 7.3％(24/330).R.microplus was positively cor-related to A.bovis(13.6％,18/132).The uncultured Anaplasma species was mainly detected in host-free ticks.A.phagocy-tophilum was detected in 24.4％of parasitic ticks and 15.8％of host-free ticks.The positive rates of host-free and parasitic ticks were 19.9％and 17.8％,respectively.These results show that H.longicornis and R.microplus were the dominant ticks in several counties of Anhui Province.H.longicornis and R.microplus as well as free and parasitic ticks all carried Anaplas-ma.

Objective:To explore the clinical efficacy and safety of flumatinib mesylate produced in China in patients with newly diagnosed chronic myeloid leukemia in chronic phase(CML-CP).Methods:32 newly diagnosed CML-CP patients admitted to the Hematology Department of the Affiliated Hospital of Southwest Medical University from March 1,2020 to March 31,2022,who had never received any tyrosine kinase inhibitor(TKI)were included in the study.The patients were treated by flumatinib mesylate 600mg once daily.The hematologic,cytogenetic and molecular responses were assessed at 3-,6-and 12-month,and adverse effects of the drug were evaluated.Results:31 patients were treated with flumatinib for≥3 months,of which 24 patients were treated for ≥ 6 months and 14 patients were treated for ≥ 12 months.At 3rd month of treatment,30 out of 31 patients achieved complete hematologic response(CHR);24 patients underwent cytogenetic testing and 22 cases achieved major cytogenetic response(MCyR),of which 21 cases achieved complete cytogenetic response(CCyR);Among 25 patients who underwent molecular testing,22 patients had BCR-ABLIS ≤ 10％,including 10 patients with BCR-ABLIS ≤ 0.1％,and 6 patients with BCR-ABLIS≤0.01％.At 6th month of treatment,23 out of 24 patients achieved CHR;17 patients underwent cytogenetic testing and all achieved CCyR;Among 23 patients who underwent molecular testing,20 patients had BCR-ABLIS ≤1％,including 16 patients with BCR-ABL1S≤0.1％and 12 patients with BCR-ABLIS ≤ 0.01％.At 12nd month of treatment,all 14 patients achieved CHR and CCyR;Among them,10 patients had BCR-ABLIS ≤ 0.1％,including 9 patients with BCR-ABLIS ≤ 0.01％.The grade Ⅲ/Ⅳ leukopenia,thrombocytopenia and anemia rates in the patients were 13.3％,20.0％and 3.3％,respectively.One patient stopped flumatinib therapy due to severe and persistent hematologic toxicity.The major non-hematologic adverse events were abnormal liver function(20％),diarrhea(10％),bone/joint pain(10％),muscle spasm(10％),rash(6.7％),acute kidney injury(6.7％)and nausea(3.3％),most of which were grade Ⅰ-Ⅱ.No patient experienced grade Ⅳnon-hematologic adverse events.No drug toxicity-related death occurred.Conclusion:Flumatinib mesglate,as the first-line treatment for newly diagnosed CML-CP,can enable the patients to achieve early and deep molecular and cytogenetic responses,and shows good safety.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective To investigate the value of intestinal fatty acid binding protein(I-FABP)in predicting the development and progression of acute-on-chronic liver failure(ACLF).Methods A retrospective analysis was performed for the clinical data of 168 patients with decompensated liver cirrhosis who were admitted to The Affiliated Hospital of Yanbian University from September 2020 to March 2023.The conditions of the patients with ACLF on admission were observed,and the patients were followed up for 6 months to identify new-onset ACLF cases.ELISA was used to measure the serum level of I-FABP on admission.The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups,and the Kruskal-Wallis H rank sum test was used for comparison between multiple groups;the chi-square test was used for comparison of categorical data between groups;the Jonckheere-Terpstra test was used for trend analysis.The Spearman correlation analysis was used to investigate the correlation between two variables,and the multivariate Cox regression analysis was used to investigate the influencing factors for new-onset ACLF during follow-up.The Kaplan-Meier curve was used to analyze the onset of ACLF in different groups,and the log-rank test was used for the analysis of such differences.The receiver operating characteristic(ROC)curve and the area under the ROC curve(AUC)were used to investigate the performance of I-FABP in predicting the development and progression of ACLF.Results Among the 168 patients enrolled in this study,there were 43 patients with ACLF and 125 patients without ACLF,among whom 19 developed ACLF during follow-up.The patients with ACLF on admission had a significantly higher level of I-FABP than those without ACLF(Z=4.359,P<0.001).The patients with new-onset ACLF had a significantly higher level of I-FABP than those without new-onset ACLF(Z=3.414,P<0.001).The level of I-FABP increased with the increase in ACLF severity grade(H=17.385,P<0.001,Ptrend<0.001).The multivariate Cox regression analysis showed that I-FABP was independently associated with new-onset ACLF during follow-up(hazard ratio=2.138,95%confidence interval[CI]:1.297-3.525,P=0.003),and the tertile of I-FABP showed a good discriminatory ability(χ2=12.16,P<0.001).The ROC curve showed that I-FABP had a good performance in predicting the development and progression of ACLF,with an area under the ROC curve of 0.854(95%CI:0.791-0.903)and 0.747(95%CI:0.661-0.820),respectively,and an optimal cut-off value of 2.07 μg/L and 1.86 μg/L,respectively.Conclusion I-FABP can be used as a biomarker to predict the development and progression of ACLF,and it may help to identify high-risk patients and improve clinical management.

Objective:To explore the cerebral cortical mechanism of intravesical electrical stimulation (IVES) on neurogenic underactive bladder (UAB).Methods:A prospective study was conducted on healthy subjects (HS) recruited in our center and patients with neurogenic UAB treated with IVES from March 2022 to June 2023 were included. HS inclusion criteria: females aged 18-60 years; the 72-hour voiding diary was normal; the urine volume was 200-400 ml, and the free urine flow rate > 20 ml/s. HS exclusion criteria: urinary and neurological related disorders; major diseases of all systems of the body; cognitive dysfunction. Inclusion criteria for UAB patients: females aged 18-60 years; neurogenic UAB due to incomplete spinal cord injury (grade D or E) with a duration of > 3 months; previous routine use of intermittent catheterization, or indication of intermittent catheterization (residual urine accounts for > 40% of functional bladder capacity). Exclusion criteria for UAB patients: decreased bladder compliance on urodynamic examination; symptomatic urinary tract infection; concomitant hydronephrosis, vesicoureteral reflux or renal insufficiency (serum creatinine greater than 1.5 times of the normal upper limit); bladder tumors; neurological related diseases; pregnant or trying to conceive; a pacemaker or defibrillator has been implanted in the body. At baseline, the 24-hour voiding diary, residual urine, voiding efficiency, first sensation of bladder filling volume and American Urological Association Symptom Index Quality of Life scores(AUA-SI-QOL)were recorded, and the resting state-functional near-infrared spectroscopy scans of the prefrontal cortex was completed in the bladder emptying state and the strong desire to void stage. The UAB group was re-evaluated after completing 20 IVES treatments. Improvement in residual urine > 50% was defined as success of IVES treatment. The differences in functional connectivity in the prefrontal lobe between the successful UAB group before and after IVES and between the successful UAB group and the HS group were compared.Results:A total of 16 HS and 18 UAB patients were included. Eleven UAB patients were successfully treated by IVES, and 7 UAB patients were failed. Compared with pre-treatment, the post-treatment residual urine volume [90.0(50.0, 120.0) ml vs. 210.0(110.0, 300.0) ml], 24-h intermittent catheterization [3.0(2.0, 4.0) times vs. 4.0(3.0, 4.0) times], first sensation of bladder filling volume [275.0(245.0, 280.0) ml vs. 295.0 (290.0, 315.0) ml] and AUA-SI-QOL score [2.0 (2.0, 3.0) vs. 4.0 (4.0, 4.0)] of the successful UAB group were significantly lower ( P<0.05), and the voiding efficiency [75.0% (69.0%, 85.0%) vs. 42.0% (35.0%, 77.0%)] was significantly higher ( P< 0.05). Before IVES, the successful UAB group compared with the HS group, internal prefrontal functional connectivity was significantly attenuated in the bladder emptying state involving 5 brain regions: bilateral dorsolateral prefrontal cortex (DLPFC), bilateral frontopolar area, and left pars triangularis. And in the strong desire to void stage significantly attenuated involving 4 brain regions: bilateral DLPFC and bilateral frontopolar area. In the successful UAB group after IVES compared with the HS group, internal prefrontal functional connectivity was significantly attenuated in the bladder emptying state involving 2 brain regions: left pars triangularis and left DLPFC. And in the strong desire to void stage involving 4 brain regions: left DLPFC, right frontopolar area, the left pars opercularis Broca's area, and the left pars triangularis. After IVES in the successful UAB group compared with pretreatment, prefrontal internal functional connectivity was significantly enhanced in the bladder emptying state involving 4 brain regions: bilateral DLPFC and bilateral frontopolar area, and in the strong desire to void stage involving 4 brain regions: bilateral DLPFC, bilateral frontopolar area. Conclusions:Significant enhancement of functional connectivity within the prefrontal lobes (bilateral DLPFC and bilateral frontopolar area) may be the cortical mechanism of IVES for neurogenic UAB.

Objective:To investigate the efficacy and safety of a wearable percutaneous tibial nerve stimulator (TTNS) for tibial neuromodulation (TNM) in the treatment of overactive bladder (OAB).Methods:This research utilizes a single-center, prospective, open clinical trial design. Patients with OAB who were treated at the urology outpatient department of Beijing Bo’ai Hospital from July 2023 to June 2024 were enrolled. All patients met the diagnostic criteria for OAB. All patients received a transcutaneous tibial nerve regulation stimulation therapy, with a frequency of 20 Hz and a pulse width of 0.2 ms. The treatment lasted for 30 minutes each session, twice daily, for a duration of 12 weeks. Follow up evaluations were conducted at weeks 4, 8, and 12 after treatment, including a 72-hour voiding diary, Overactive Bladder Symptom Score (OABSS), patient perception of bladder condition scale (PPBC-S) score, American Urological Association Symptom Index (AUA-SI) score, American Urological Association Symptom Index Quality of Life Score (AUA-SI-QOL) score, vital signs, and adverse events.Results:This study included 68 patients, with 28 males and 40 females. Their mean age was (49.6±9.0) years old, the body mass index was(23.2 ± 2.5) kg/m 2. The duration of the disease was(42.0±14.4)months. After 12 weeks of intervention, patient's daily urination frequency decreased from (18.5 ± 3.9) times to (10.3 ± 4.5) times, nocturia frequency decreased from (6.5±2.2) times to (3.9±2.0) times, daily urine leakage decreased from (796.5±140.0) ml to (534.8±135.8)ml, OABSS decreased from (12.6±2.8) to (9.8±3.8), PPBC-S decreased from (5.5±0.6) to (3.8±1.2), AUA-SI decreased from (25.5±2.2) to (16.6±3.6), and AUA-SI-QOL decreased from (5.5±0.5) to (3.7±1.1). The differences in the above indicators before and after treatment were statistically significant ( P<0.05). During the treatment process, there were no serious adverse events related to the equipment, and no neurological related adverse events such as numbness or tingling occurred. Conclusions:The application of wearable percutaneous tibial nerve stimulators in TNM can effectively alleviate OAB symptoms like frequent urination and urgency, with minimal adverse reactions, offering a new treatment option for OAB patients.