ObjectiveTo investigate the risk factors for pyogenic liver abscess （PLA） comorbid with sepsis by analyzing clinical features， and to construct a predictive model. MethodsA retrospective analysis was performed for 489 patients who were hospitalized and diagnosed with PLA in The Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2023， and according to the presence or absence of sepsis， they were divided into sepsis group with 306 patients and non-sepsis group with 183 patients. Related data were collected， including general information， laboratory markers， and outcome measures. The patients were further divided into a training set of 342 patients and a validation set of 147 patients at a ratio of 7∶3， and the training set was used for screening of variables and construction of a predictive model， while the validation set was used to test the performance of the model. An LASSO regression analysis was used for the screening of variables， and a multivariate Logistic regression analysis was used to construct the predictive model and plot a nomogram. The calibration curve， the receiver operating characteristic （ROC） curve， and the decision curve analysis were used for the validation of the model， and internal validation was performed for assessment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical variables between groups. ResultsThere were significant differences between the sepsis group and the non-sepsis group in pulse rate， mean arterial pressure， duration pf symptoms， comorbidity of liver cirrhosis or malignant tumor， leukocyte count， neutrophil count， lymphocyte count， platelet count （PLT）， activated partial thromboplastin time， fibrinogen， C-reactive protein， aspartate aminotransferase， alanine aminotransferase， albumin， total bilirubin （TBil）， creatinine， potassium， and prognostic nutritional index （PNI） （all P<0.05）. In the training set， the LASSO regression analysis identified four predictive factors of pulse rate， PLT， TBil and PNI， and the multivariate Logistic regression analysis showed that pulse rate （odds ratio ［OR］=1.033， 95% confidence interval ［CI］： 1.006‍ ‍—‍ ‍1.061， P=0.018）， PLT （OR=0.981， 95%CI： 0.975‍ ‍—‍ ‍0.987， P<0.001）， TBil （OR=1.086， 95%CI： 1.053‍ ‍—‍ ‍1.125， P<0.001）， and PNI （OR=0.935， 95%CI： 0.882‍ ‍—‍ ‍0.988， P=0.019） were independent influencing factors for the risk of sepsis in patients with PLA. The model constructed based on these factors showed a good predictive ability， with an area under the ROC curve of 0.948 （95%CI： 0.923‍ ‍—‍ ‍0.973） in the training set and 0.912 （95%CI： 0.848‍ ‍—‍ ‍0.976） in the validation set. The decision curve analysis showed that the model has a good net benefit within the range of 0.3‍ ‍—‍ ‍0.9 for threshold probability. ConclusionThe nomogram prediction model constructed based on pulse rate， PLT， TBil， and PNI has a certain clinical value and can well predict the risk of sepsis in patients with PLA.

Objective To investigate the population distribution of non-alcoholic fatty liver disease before and after renaming and the association between the types of metabolic risk factors(MRF)for metabolic dysfunction-associated steatotic liver disease(MASLD)and advanced liver fibrosis.Methods This study was conducted among 515 patients who were admitted to The Affiliated Hospital of Xuzhou Medical University and Wuxi Fifth People's Hospital from January 2019 to January 2022 and had hepatocyte steatosis≥5%by liver biopsy.Among these patients,2 patients did not meet the diagnostic criteria for nonalcoholic fatty liver disease(NAFLD)and metabolic associated fatty liver disease(MAFLD),respectively,and were classified as steatotic liver disease(SLD)with other specific causes,and the other 513 patients were divided into MASLD group with 275 patients,comorbid group with 216 patients(MASLD comorbid with other liver diseases),and cryptogenic SLD group with 22 patients.The above groups were compared in terms of clinical features,laboratory markers,and advanced liver fibrosis.The MASLD patients with different types of MRF were compared in terms of clinical features,laboratory markers,and advanced liver fibrosis,and the risk factors for advanced liver fibrosis in patients with MASLD were analyzed.The Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups and further comparison between two groups;the chi-square test was used for comparison of categorical data between multiple groups,and Bonferroni correction was used for further comparison between two groups.The logistic regression analysis was used to identify the risk factors for liver fibrosis.Results Among the 515 patients with SLD,297 patients(57.7%)met the diagnostic criteria for NAFLD,among whom 22 were classified as cryptogenic SLD and 275 met the diagnostic criteria for MASLD,and 467(90.7%)were diagnosed with MAFLD.There were significant differences between the three groups in sex,body mass index(BMI),gamma-glutamyl transpeptidase,triglyceride,cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,fasting plasma glucose,NAFLD fibrosis score(NFS),fibrosis-4(FIB-4),and F3-4(all P＜0.05).Compared with the MASLD group and the cryptogenic SLD group,the comorbid group had the highest proportion of patients with advanced liver fibrosis(P＜0.001).With the increase in the type of MRF,the patients tended to have an older age,a significantly higher proportion of female patients,a higher possibility of hypertension and diabetes,and higher levels of metabolic parameters including BMI,blood lipids,and blood glucose(all P＜0.05).With the increase in the types of MRF in MASLD patients,they tended to have significantly higher noninvasive fibrosis scores(NFS and FIB-4)and a significantly higher proportion of patients with advanced liver fibrosis(P＜0.05).The multivariate logistic regression analysis showed that age≥50 years(odds ratio[OR]=2.622,95%confidence interval[CI]:1.091-6.300,P=0.031)and the increase in the type of MRF(OR=1.876,95%CI:1.194-2.947,P=0.006)were independent risk factors for MASLD with severe liver fibrosis.Conclusion The new definition of MASLD is based on the positive identification of MRF,and the reclassified population of MASLD is smaller than that of MAFLD,with little difference from that of NAFLD.In addition,age≥50 years and the increase in the type of MRF are independent risk factors for MASLD with advanced liver fibrosis.

Objective:To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS).Methods:A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome ( SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by Medical Ethics Committee of the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). Results:The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46, XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c. 1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister′s first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+ PM4+ PP3_Moderate+ PP4). Conclusion:The c. 1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians′ thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction

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 the role of eosinophil associated ribonuclease A family member 2 (Ear2) in the pathogenesis of lupus and its possible mechanisms involved in renal damage by conditional knockout of myeloid cells in mice.Methods:An Ear2 myeloid conditional knockout mouse model was constructed using CRISP/Cas9 technology, and PCR was applied to identify mice genotype. The experiment was divided into 3 groups: CKO+R848 group, control+R848 group, and control group. R848 (Resiquimod) was used to treat the knockout mice and homozygous control mice to evaluate the occurrence of lupus-like features. Quantitative real-time PCR was performed to detect the expression of Toll-like receptor 7/8 (TLR7/8) and its related inflammatory factors in the kidneys of mice. Flow cytometry (FCM) was used to detect the proportion of patrolling monocytes in the kidneys, and immunofluorescence was used to analyze the spatial distribution of Ear2 and PMOs in renal tissues. In addition, R848 was used to stimulate myeloid cells of conditional knockout (CKO) and control mice in vitro, with changes in the proportion of PMOs detected by flow cytometry. Variance (ANOVA) was used to compare the differences between groups, t-test was used for two-by-two comparisons, and one-way analysis of ANOVA was used for comparisons between multiple groupscant. Results:PCR of myeloid conditioned knockout Ear2 mice showed a genotype of Lyz2 ki/wtEar2 fl/fl and significant down-regulation of Ear2 mRNA levels in bone marrow cells of the knockout mice [(1.03±0.26) vs. (0.22±0.15), t=6.65, P<0.001]. Compared with the control+R848 group, lupus related phenotype presentations of mice was improved and the survival rate tended to increase in the CKO+R848 group (6/10 vs. 7/8, χ2=1.51, P=0.220). The pathological results examination suggested that renal lesions of mice in the CKO+R848 group were also attenuated. The expression level of TLR7 was reduced in the renal tissues of CKO+R848 mice [(1.02±0.09) vs. (0.53±0.04), t=5.13, P=0.003], accompanied by a decrease in PMOs infiltration [(62.00±3.37)% vs. (52.36±0.68)%, t=2.80, P=0.023], and immunofluorescence results showed that Ear2 and PMOs were co-localized in renal tissues. In vitro, R848 stimulation caused an increase in the proportion of PMOs in the control group [(3.99±0.59)% vs. (33.48±1.38)%, t=-33.84, P<0.0001], yet had no effect on CKO mice [(14.33±1.72)% vs. (16.10±1.44)%, t=-1.37, P=0.220]. Conclusion:Conditional knockdown of Ear2 attenuates the development of lupus in mice, especially renal impairments, which is related to the inhibition of TLR7 pathway and reduction of local infiltration of PMOs.

To summarize the nursing experience of a pediatric patient with multiple organ burns in the abdominal cavity and liver laceration caused by a fireworks explosion.The following nursing points were implemented:immediate activation of a multidisciplinary trauma rescue team upon admission to initiate emergency measures for traumatic shock;implementation of target-oriented fluid management to expedite postoperative intestinal function recovery;active control of abdominal infection to minimize the risk of septic shock;thorough and accurate assessment was conducted to prevent postoperative complications such as gastrointestinal hemorrhage,bile-leakage,gallbladder perforation,and delayed intestinal necrosis;nutritional screening and assessment was performed to develop personalized nutritional support programs;emphasis should be placed on pain assessment to implement individualized analgesia measures;the provision of high-quality psychological support focusing on addressing psychological trauma.The child was successfully discharged 36 days after surgery and exhibited satisfactory recovery during the two-month follow-up period.

Objective To explore the effects of repetitive transcranial magnetic stimulation(rTMS)combined with synchronous working memory training on memory,attention,executive function and other cognitive functions in stroke patients.Methods A total of 100 stroke inpatients and outpatients admitted in Department of Rehabilitation Medicine of Hongqi Hospital Affiliated to Mudanjiang Medical College from January 2022 to May 2023 were enrolled and randomly divided into a synchronous group(simultaneous rTMS and working memory training),a rTMS group,a working memory training group,and a control group(no cognitive training),there were 25 case in each group.Stroop test,Rivermead behavioral memory test,Montreal cognitive assessment(MoCA),modified Barthel index(MBI)test,and Fugl-Meyer test were applied before and after treatment.Results There were no significant differences in above test scores among the four groups before treatment(P＞0.05).After treatment,Stroop test showed that the synchronization group had significantly higher accuracy rates of the baseline phase and the conflict phase than the other three groups(P＜0.05),shorter reaction time of the baseline phase than the working mem-ory training group and the control group(1043.76±260.38 ms vs 1299.36±468.86 ms and 1418.68±412.25 ms,P＜0.05),and shorter reaction time of the conflict phase than the control group(P＜0.05).The synchronization group scored statistically higher scores than the other three groups in the Rivermead behavioral memory test,MoCA test,modified Barthel test,and Fugl-Meyer test(P＜0.05).Conclusion rTMS combined with synchronous working memory training can effectively improve the cognitive function in stroke patients.

Objective:To explore the specific role and molecular mechanism of octamer-binding transcription factor 4 (Oct4) in promoting the progression of esophageal squamous cell carcinoma and radioresistance.Methods:The Gene Expression Profile Data Dynamic Analysis (GEPIA) database was used to analyze the expression differences of the Oct4 gene in different types of tumor tissues and their corresponding adjacent normal tissues. The clinical data and surgical resection tissue specimens of 196 patients with esophageal squamous cell carcinoma who received surgery combined with radiotherapy at Henan Provincial Chest Hospital from January 2013 to May 2022 were collected. Immunohistochemistry was used to detect the expression of Oct4 protein in the tumor and adjacent tissues. The lentiviral packaging system was used to construct esophageal squamous cell carcinoma cell lines that up-regulated or down-regulated Oct4. The cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, the scratch test was used to detect the cell migration ability, and the clone formation test was used to detect the cell radiosensitivity. Immunofluorescence experiment was used to detect DNA damage level, and Western blot was used to detect the expressions of Oct4, human phosphorylated histone (γ-H2AX), E-cadherin, N-cadherin, vimentin, and zinc finger E box binding homology box 1 (ZEB1).Results:The analysis of GEPIA database showed that the expression level of Oct4 mRNA in esophageal carcinoma was higher than that in paracancerous tissues. The expression level of Oct4 protein in tumor tissues was 78.35±1.42, which was higher than that in adjacent tissues (16.27±0.49). The survival time of patients with a high expression of Oct4 was significantly shorter than that of patients with a low expression of Oct4 (25.40 and 47.00 months). Compared with the control group, the proliferation ability of KYSE510 cells in the Oct4 up-regulated group was enhanced after 72-h culture, and the cell migration ability of these cells was also enhanced, with the migration rate being (41.67±1.20)% vs (23.67±1.86)% after 24-h culture. The radiosensitivity of cells in this group decreased, with the radiosensitivity enhancement ratio being 0.69±0.06 vs 1.00±0.02. After radiotherapy, the expressions of γ-H2AX and E-cadherin decreased, while the expressions of ZEB1, vimentin and N-cadherin increased. Compared with the control group, the proliferation ability of KYSE150 cells in the Oct4 down-regulated groups 1 and 2 decreased (absorbance being 2.51±0.17, 2.38±0.16, and 3.33±0.07, respectively, P＜0.01) after 72-h culture, and the migration ability also decreased, with the migration rate being (13.33±0.88)%, (13.00±1.00)%, and (40.33±2.03)%, respectively (all P＜0.001), after 24-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.34±0.11,1.24±0.07, and 1.00±0.02, respectively (all P＜0.05). After radiotherapy, the expressions of γ-H2AX and E-cadherin increased, while the expressions of ZEB1, vimentin and N-cadherin decreased. Compared with the control group, the proliferation ability of KYSE510 cells in the ZEB1 down-regulated group decreased [absorbance being 1.33±0.15 vs 1.81±0.16 ( P=0.002)] after 72-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.37±0.11 vs 1.00±0.01 ( P=0.037), and after radiotherapy the expression of γ-H2AX increased. Conclusion:Oct4 is involved in the regulation of epithelial-mesenchymal transformation of esophageal squamous cell carcinoma, which promotes the proliferation, migration, and radioresistance of esophageal squamous cell carcinoma.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Objective:To explore the clinical and genetic characteristics of a fetus diagnosed with Congenital myasthenic syndrome type 16 (CMS16).Methods:A couple who had visited Tianjin Medical University General Hospital in February 2018 due to "adverse outcome of two pregnancies" was selected as the study subject. Clinical data was gathered. Peripheral blood and amniotic fluid samples were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Low-depth whole-genome sequencing was carried out to detect copy number variation (CNV) in the fetus.Results:The couple′s first pregnancy had resulted in a miscarriage at 27 + 5 weeks, when ultrasound had revealed pleural effusion and polyhydramnios in the fetus. Their second pregnancy was terminated at 30 + 5 weeks due to fetal hand malformations, polyhydramnios and pleural fluid. Both couple had denied family history of genetic conditions. For their third pregnancy, no CNV abnormality was detected, whilst a compound heterozygous variants, including a maternally derived c. 3172C>T (p.R1058W) and paternal c. 1431delG (p.K477fs*89) in the SCN4A gene were detected. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 3172C>T (p.R1058W) was predicted as a likely pathogenic variant (PM1+ PM2_supporting+ PP3+ PP4), whilst the c. 1431delG (p.K477fs*89) was predicted as a pathogenic variant (PVS1+ PM2_supporting+ PP4). Conclusion:The c. 3172C>T (p.R1058W) and c. 1431delG (p.K477fs*89) compound heterozygous variants of the SCN4A gene probably underlay the CMS16 in the third fetus.