Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Objective To explore the correlation between the test panel of serum CC chemokine ligand 3(CCL3),soluble podoplanin(sPDPN),fatty acid-binding protein 5(FABP5)and the severity of lung injury and clinical outcomes in children with severe pneumonia.Methods A total of 168 children with severe pneumonia who visited our hospital from January 2022 to January 2023 were included in this study as severe group.The patients were assigned to good outcome group(137 cases)or poor outcome group(31 cases)based on their prognosis.Additional 80 children with mild or moderate pneumonia were treated as non-severe group.In addition,80 children who underwent health checkup were included as control group.Baseline data such as body mass index and duration of disease were observed and recorded for all children.Enzyme linked immunosorbent assay(ELISA)was applied to detect the expression levels of C-reactive protein(CRP),procalcitonin(PCT),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),CCL3,sPDPN,and FABP5 in the serum of all children.The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)score and Lung Injury Prediction(LIPS)score were rated to evaluate the degree of lung injury.Multivariate logistic regression was used to analyze the impact of various factors on the poor outcome of children with severe pneumonia.Spearman correlation was applied to analyze the correlation between the expression levels of CCL3,sPDPN,FABP5 and poor outcome,the severity of lung injury,APACHE Ⅱ score,and LIPS score in children with severe pneumoniae.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of CCL3,sPDPN,and FABP5 expression levels for poor outcome in children with severe pneumonia.Z-test was used to compare the differences in area under the curve(AUC).Results The baseline data such as duration of disease,body mass index,age,and sex did not show significant differences among the control group,non-severe group,and severe group(P＞0.05).The levels of serum CRP,PCT,IL-6,TNF-α,CCL3,sPDPN increased,while the level of FABP5 decreased gradually from the control group to non-severe group,and severe group(P＜0.05).The patients with poor outcomes showed higher serum levels of CRP,PCT,IL-6,TNF-α,CCL3,sPDPN,APACHE Ⅱ score,and LIPS score but lower FABP5 level compared to the patients with good outcomes(P＜0.05).TNF-α,CCL3,sPDPN,APACHE Ⅱ,and LIPS scores were independent risk factors for poor outcomes in children with severe pneumonia,while FABP5 level was independent protective factor for poor outcomes in children with severe pneumonia(P＜0.05).The levels of CCL3 and sPDPN were positively correlated with APACHE Ⅱ score and LIPS score,while FABP5 was negatively correlated with APACHE Ⅱ score and LIPS score(P＜0.05).The AUC of CCL3,sPDPN,and FABP5 alone was 0.802,0.864,and 0.859 respectively for predicting poor prognosis in children with severe pneumonia.The test panel of CCL3+sPDPN+FABP5 was superior to CCL3,sPDPN,or FABP5 alone(Zcombination-CCL3=3.842,Zcombination-sPDPN=2.585,Zcombination-FABP5=2.957,P＜0.05).Conclusions The serum levels of CCL3 and sPDPN are positively correlated with the severity of lung injury,while FABP5 is negatively correlated with the severity of lung injury in children with severe pneumonia.The test panel of CCL3+sPDPN+FABP5 is valuable for predicting poor outcomes in children with severe pneumonia.

Objective To observe the effects of Chaihu Longgu Muli Decoction on oxidative stress in hippocampus and hypothalamic-pituitary-adrenal(HPA)axis hormone levels of rats with generalized anxiety disorder(GAD);To explore its mechanism of alleviating anxiety in GAD rats.Methods A total of 72 Wistar rats were randomly divided into blank group(12 rats)and modeling group(60 rats).Chronic restraint stress was used to establish the GAD model.The successfully modeled rats were randomly divided into model group,diazepam group(1 mg/kg)and TCM low-,medium-and high-dosage groups(Chaihu Longgu Muli Decoction 6,12,24 g/kg).The administration groups were given corresponding drugs by gavage for 14 consecutive days.Open field experiment and elevated cross maze experiment were used to observe indexes in rat behavior,HE staining was used to observe the morphology of hippocampal tissue,ELISA was used to detect the contents of serum corticotropin releasing hormone(CRH),adrenocorticotropic hormone(ACTH)and corticosterone(CORT),biochemical kits were used to detect the contents of malondialdehyde(MDA),catalase(CAT)and superoxide dismutase(SOD)in hippocampal tissue,RT-PCR was used to detect the mRNA expressions of MEK,ERK,Bax and Bcl-2 in hippocampal tissue,Western blot was used to detect the protein expressions of MEK,p-MEK,ERK,p-ERK,Bax and Bcl-2 in hippocampal tissue.Results Compared with the blank group,the rats in the model group had a significantly slower growth rate of body msss,loose stool,dark hair,significant hair removal and extreme agitation;the activity time and distance in the central area were significantly reduced(P<0.01),the percentage of time,frequency and distance of entering the open arm were significantly reduced(P<0.01);with structural degeneration of hippocampal neurons,changes in cell morphology,disordered arrangement and edema of surrounding tissues;the contents of serum CRH,ACTH and CORT significantly increased(P<0.01);the MDA content in hippocampal tissue significantly increased(P<0.01),CAT and SOD contents significantly decreased(P<0.01),p-MEK and p-ERK protein expressions significantly decreased(P<0.01),Bax mRNA and protein expressions significantly increased(P<0.01),Bcl-2 mRNA and protein expressions significantly decreased(P<0.01).Compared with the model group,the body mass growth rate of diazepam group and each dosage of TCM group increased,and the symptoms of loose stool,hair removal,anxiety and huddling were improved;the activity time and distance in the central area of rats in the diazepam group and TCM medium-and high-dosage groups significantly increased(P<0.01),and the percentage of time,frequency and distance of entering the open arm significantly increased(P<0.05,P<0.01);the contents of serum CRH,ACTH and CORT significantly decreased(P<0.05,P<0.01);the MDA content in the hippocampal tissue in diazepam group and TCM high-dosage group significantly decreased(P<0.01),while the CAT and SOD contents significantly increased(P<0.05,P<0.01),the protein expressions of p-MEK and p-ERK in hippocampal tissue in diazepam group and TCM medium-and high-dosage group significantly decreased(P<0.01),Bax mRNA and protein expressions were significantly decreased(P<0.01),and Bcl-2 mRNA and protein expressions significantly increased(P<0.05,P<0.01).There was no statistical significance in the expressions of MEK,ERK mRNA and protein among the groups(P>0.05).Conclusion Chaihu Longgu Muli Decoction can alleviate anxiety in GAD rats by inhibiting HPA axis hormone release and MEK/ERK signaling pathway activation,improving neuroendocrine levels,and reducing hippocampal oxidative stress response.

Objective:To explore the genetic basis for a girl with primary microcephaly and growth retardation.Methods:A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278).Results:DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c. 2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. Conclusion:Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.

OBJECTIVE: To explore the genetic basis for a girl with primary microcephaly and growth retardation. METHODS: A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278). RESULTS: DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c.2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. CONCLUSION Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.
Female ; Humans ; Cell Cycle Proteins ; Heterozygote ; Microcephaly/genetics* ; Mutation ; Nerve Tissue Proteins/genetics* ; Pedigree

Objective To develop a core outcome set(COS)for treatment of progressive vitiligo in Uyghur medicine,and to standardize the selection and reporting of outcome measures in relevant studies.Methods Based on the existing core outcome domain set of randomized controlled trials for vitiligo,additional outcome indicators reflecting the advantages and characteristics of Uyghur medical treatment were developed.Specific indicators for Uyghur medical treatment of progressive vitiligo were collected through literature review and semi-structured questionnaire surveys,and then a list of indicators were formed.The Delphi survey and consensus meetings were used to select core indicators.Results A total of 54 studies were included,and 86 questionnaires were collected.Through literature review and questionnaire surveys,a list of 28 indicators were obtained.After two rounds of Delphi survey and one consensus meeting,12 outcome indicators in 7 domains were finally determined,including vitiligo lesion area,repigmentation,disease control time,maintenance of repigmentation,recurrence rate,immune indicators,psychological health,patients' quality of life,adverse events,adverse reaction incidence,liver and kidney function monitoring,and Uyghur medicine syndrome differentiation of mucus.Additionally,some measurement tools for certain indicators were recommended.Conclusion The development of the COS for vitiligo treatment in Uyghur medicine helps to comprehensively evaluate the efficacy of Uyghur medicine,and will provide a model for establishing efficacy evaluation methods that conform to the characteristics of ethnic minority medicine.

OBJECTIVE: To construct machine learning prediction model for sepsis-associated encephalopathy (SAE), and analyze the application value of the model on early identification of SAE risk in elderly septic patients. METHODS: Patients aged over 60 years with a primary diagnosis of sepsis admitted to intensive care unit (ICU) from 2008 to 2023 were selected from Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2). Demographic variables, disease severity scores, comorbidities, interventions, laboratory indicators, and hospitalization details were collected. Key factors associated with SAE were identified using univariate Logistic regression analysis. The data were randomly divided into training and validation sets in a 7 : 3 ratio. Multivariable Logistic regression analysis was conducted in the training set and visualized using a nomogram model for prediction of SAE. The discrimination of the model was evaluated in the validation set using the receiver operator characteristic curve (ROC curve), and its calibration was assessed using calibration curve. Furthermore, multiple machine learning algorithms, including multi-layer perceptron (MLP), support vector machine (SVM), naive bayes (NB), gradient boosting machine (GBM), random forest (RF), and extreme gradient boosting (XGB), were constructed in the training set. Their predictive performance was subsequently evaluated on the validation set. Taking the XGB model as an example, the interpretability of the model through the SHapley Additive exPlanations (SHAP) algorithm was enhanced to identify the key predictive factors and their contributions. RESULTS: A total of 2 204 septic patients were finally enrolled, of whom 840 developed SAE (38.1%). A total of 21 variables associated with SAE were screened through univariate Logistic regression analysis. Multivariable Logistic regression analysis showed that endotracheal intubation [odds ratio (OR) = 0.40, 95% confidence interval (95%CI) was 0.19-0.88, P < 0.001], oxygen therapy (OR = 0.76, 95%CI was 0.53-0.95, P = 0.023), tracheotomy (OR = 0.20, 95%CI was 0.07-0.53, P < 0.001), continuous renal replacement therapy (CRRT; OR = 0.32, 95%CI was 0.15-0.70, P < 0.001), cerebrovascular disease (OR = 0.31, 95%CI was 0.16-0.60, P < 0.001), rheumatic disease (OR = 0.44, 95%CI was 0.19-0.99, P < 0.001), male (OR = 0.68, 95%CI was 0.54-0.86, P = 0.001), and maximum anion gap (AG; OR = 0.95, 95%CI was 0.93-0.97, P < 0.001) were associated with an decreased probability of SAE, and age (OR = 1.05, 95%CI was 1.03-1.06, P < 0.001), acute physiology score III (APSIII; OR = 1.02, 95%CI was 1.01-1.02, P < 0.001), Oxford acute severity of illness score (OASIS; OR = 1.04, 95%CI was 1.03-1.06, P < 0.001), and length of hospital stay (OR = 1.01, 95%CI was 1.01-1.02, P < 0.001) were associated with an increased probability of SAE. A nomogram model was constructed based on these variables. In the validation set, ROC curve analysis showed that the model achieved an area under the ROC curve (AUC) of 0.723, and the calibration curve showed good consistency between the predicted probability of the model and the observed probability. Among the machine learning algorithms, including MLP, SVM, NB, GBM, RF, and XGB, the SVM model and RF model demonstrated relatively good predictive performance, with AUC of 0.748 and 0.739, respectively, and the sensitivity was both exceeding 85%. The predictive performance of the XGB model was explained through SHAP analysis, and the results indicated that APSIII score (SHAP value was 0.871), age (SHAP value was 0.521), and OASIS score (SHAP value was 0.443) were important factors affecting the predictive performance of the model. CONCLUSIONS The machine learning-based SAE prediction model exhibits good predictive capability and holds significant application value for the early identification of SAE risk in elderly septic patients.
Humans ; Machine Learning ; Aged ; Sepsis-Associated Encephalopathy ; Sepsis/complications* ; Intensive Care Units ; Logistic Models ; Middle Aged ; Male ; ROC Curve ; Female ; Bayes Theorem ; Nomograms ; Support Vector Machine ; Algorithms