Objective:Early identification of the sepsis patients accompanied by acute kidney injury (AKI) who were at high risk of invasive mechanical ventilation within 48 hours would help to improve the prognosis.Methods:The clinical information was collected from the sepsis patients with AKI who were admitted at Dongyang People’s Hospital from January 2011 to Octber 2023. The enrolled cases were divided into training set and validation set. The independent risk factors related to invasive mechanical ventilation within 48 hours were obtained by univariable analysis and multivariable logistic regression analysis in the training set, and then a nomogram model was established. The model was evaluated for its discrimination power by the area under the receiver operating characteristic curve (AUC), calibration degree by GiViTI calibration graph and clinical benefit by decision curve analysis both in the training set and validation set. Also, two models (based on SOFA score and NEWs score, respectively) in two patient sets and four models based on machine learning methods (SVM, C5.0, XGBoos and integration method) in validation set were established and compared to logistic model for AUCs by Delong test.Results:A total of 773 cases were finally enrolled in this study. The risk factors for invasive mechanical ventilation within 48 hours were lactate, pro-bnp, D-dimer, saturation of peripheral oxygen and lung infection. The AUC of logistic nomogram model was 0.845 in the training set. In the validation set, the AUC was 0.880, also with good calibration degree and clinical benefit. The AUCs of the models in the training and validation sets based on SOFA score were 0.703 and 0.763, respectively, significantly lower than the logistic model ( P less than 0.05). In addition, the AUCs of the models based on the NEWs score were significantly lower both in the training set (AUC of 0.665, P <0.001) and validation set (AUC of 0.718, P=0.002) than the logistic model. Finally, the AUCs of the models were 0.780 for SVM method, 0.835 for C5.0, 0.798 for XGBoost and 0.813 for integration method, comparable to logistic model ( P > 0.05). Conclusions:The logistic prediction model based on lactate, pro-bnp, D-dimer, saturation of peripheral oxygen and lung infection can efficiently predict the risk for invasive mechanical ventilation within 48 hours among the sepsis patients with AKI.

Objective:To investigate the efficacy of different laparoscopic surgeries for gastrointestinal stromal tumors (GIST) of gastric cardia and fundus.Methods:The retrospective cohort study was conducted. The clinicopathological data of 251 patients with GIST of gastric cardia and fundus who underwent laparoscopic radical resection in 14 medical centers, including Guangdong Provincial People′s Hospital et al, from December 2007 to December 2021 were collected. There were 123 males and 128 females, aged 58(24,87)years. Observation indicators: (1) treatment; (2) clinicopathological data of patients undergoing different laparoscopic surgeries; (3) subgroup analysis for special laparoscopic techniques. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test or ANOVA. Measure-ment data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test or Kruskal-Wallis H test. Count data were described as absolute numbers or percentages. Comparison of ordinal data was conducted using the rank sum test. Results:(1) Treatment. Of the 251 patients,202 cases underwent gastric wedge resection, 26 cases underwent special laparoscopic techniques including 10 cases with serotomy and dissection and 16 cases with transluminal gastrectomy, 23 cases underwent structural gastrectomy including 6 cases with total gastrectomy and 17 cases with proximal partial gastrectomy. There were 24 patients had postoperative complications after surgery. (2) Clinicopathological data of patients undergoing different laparoscopic surgeries. The gender (male, female), age, tumor diameter, operation time, volume of intraoperative blood loss, length of incision, time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, duration of postoperative hospital stay, cases with perioperative complications, cases with mitotic count as ≤5/50 high power field, 6?10/50 high power field, >10/50 high power field, cases be classified as very low risk, low risk, medium risk, high risk according to the National Institutes of Health risk classification, cases with tumor located at fundus and gastric cardia were 93, 109, (59±11)years, 3.50(0.40,10.00)cm, 88.00(25.00,290.00)minutes,20.00(25.00,290.00)mL, 4.00(2.00,12.00)cm, 3.00(1.00,9.00)days, 4.00(1.00,16.00)days, 5.00(1.00,18.00)days, 14, 164, 31, 7, 47, 83, 50, 22, 30, 172 in patients undergoing gastric wedge resection, respectively. The above indicators were 19, 7, (49±14)years, 2.55(0.20,5.00)cm, 101.00(59.00,330.00)minutes, 27.50(2.00,300.00)mL, 4.50(0,6.00)cm, 2.50(1.00,10.00)days, 4.00(1.00,16.00)days, 6.00(1.00,18.00)days, 3, 20, 5, 1, 15, 5, 2, 4, 24, 2 in patients undergoing special laparos-copic techniques, and 11, 12, (52±10)years, 5.00(0.80,10.00)cm, 187.00(80.00,325.00)minutes, 50.00(10.00,300.00)mL, 6.00(4.00,12.00)cm, 4.00(2.00,8.00)days, 6.00(3.00,14.00)days, 8.00(2.00,18.00)days, 7, 11, 5, 7, 2, 6, 6, 9, 13, 10 in patients undergoing structural gastrectomy. There were significant differences in the above indicators among the three groups of patients ( χ2=6.75, F=10.19, H=17.71, 37.50, 35.54, 24.68, 16.09,20.20, 13.76, χ2=13.32, Z=28.98, 32.17, χ2=82.14, P<0.05). (3) Subgroup analysis for special laparoscopic techniques. The time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake, classification of tumor location (endophytic type, exophytic type, parietal type) were 4.50(1.00,10.00)days, 8.00(3.00,12.00)days, 0, 8, 2 in patients undergoing serotomy and dissection, versus 2.00(1.00,4.00)days, 3.00(1.00,6.00)days, 16, 0, 0 in patients undergoing transluminal gastrectomy. There were significant differences in time to postoperative initial whole liquid food intake, time to postoperative initial semi-liquid food intake between them ( Z=-2.65, -3.16, P<0.05); and there was a significant difference in classification of tumor location between them ( P<0.05). Conclusions:Gastric wedge resection is the most commonly used laparoscopic technique for GIST of gastric cardia and fundus. The application of special laparoscopic techniques is focused on the GIST of cardia to preserve the function of the cardia.

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

ObjectiveTo explore the related factors of troublemaking behaviors among patients with mental disorders induced by amphetamine-type stimulants （ATS）， and to provide references for the formulation of relevant intervention measures for ATS-induced mental disorders. MethodsA total of 105 patients who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） for ATS-induced mental disorders were included， and classified into troublemaking group and non-troublemaking group. The general demographic data and clinical data of the selected individuals were collected， and all patients were assessed using Social Support Rating Scale （SSRS）. Then univariate analysis and multivariate Logistic regression model were used to screen the related factors of troublemaking behaviors. ResultsThe scores of SSRS， objective support dimension and social support utilization dimension were significantly lower in troublemaking group than those in non-troublemaking group， with statistical differences ［（24.10±6.59） vs. （28.94±5.59）， t=3.364， P=0.001； （5.50±1.96） vs. （8.20±2.13）， t=5.183， P<0.01； （4.60±2.26） vs. （6.28±1.90）， t=3.435， P=0.001］. Multivariate Logistic regression analysis showed that male （OR=6.061， P=0.014） was a risk factor， while high social support level （OR=0.873， P=0.018） was the protective factor for troublemaking behaviors among patients with ATS-induced mental disorders. ConclusionPatients with ATS-induced mental disorders of the males and with low social support level are at high risk of troublemaking behaviors.

Objective: To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR₁) and negative minimal residual disease (MRD^-) . Methods: A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR₁/MRD^- from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy. Results: A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR₁/MRD^- was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes. Conclusion Allo-HSCT for candidate patients without further consolidation when CR₁/MRD^- was attained was feasible.

Objective To conduct mutation screening of SCN1A 3′ untranslated region (UTR) on Dravet syndrome (DS) patients without mutations in the SCN1A coding region and promoter region, and functional analysis of the variant from DS patients.Methods Twenty-eight DS patients without mutations in the SCN1A coding region and promoter region were screened for SCN1A 3′ UTR mutations using PCR and direct sequencing.Functional analysis of the detected mutation was done via luciferase assay, mRNA stability analysis and RNA electrophoretic mobility shift assay (RNA-EMSA).Results A novo variant (c.*20A>G) in SCN1A 3′ UTR was found in one DS patient.The variant (c.*20A>G) reduced the luciferase gene xpression by 30% through increasing the affinity of pluripotent embryonal carcinoma cell line NT2/cytoplasmic protein binding and reducing luciferase gene mRNA stability (t=8.5,P<0.01).Conclusions A functional variant was detected from one patient with DS.This variant negatively regulated the gene expression by increasing the affinity of pluripotent embryonal carcinoma cell line NT2/cytoplasmic protein binding and reducing mRNA stability.

Objective: To compare and analyze the epidemiological characteristics of hospitalized elderly, young and middle-aged patients with severe burn in recent years, so as to provide reference for the prevention and treatment of elderly patients with severe burn. Methods: Relying on the entry system of epidemiological case data and biological sample of severe burn from multicenter in clinic, medical records of patients with severe burn, aged above 18, hospitalized in 8 burn wards from January 2012 to December 2015 were collected. Six hundred and fifteen patients who were more than 18 years old and less than or equal to 65 years old were included in young and middle-aged group (YM). Eighty-two patients aged more than 65 years old were included in elderly group (E). Data of age, gender, residence, education level, cause of injury, location of injury, season of injury, total burn area, occurrence and area of full-thickness burn injury, wound site, inhalation injury incidence and severity, post burn admission time, proportion of delayed resuscitation, proportion of escharectomy or tangential excision and skin grafting, preinjury systemic disease, system complication during hospitalization, length of hospital stay, outcome of treatment, and reason of abandoning treatment of patients were analyzed. Data were processed with chi-square test and Mann-Whitney U test. The odds ratios of preinjury systemic disease, system complication during hospitalization, and adverse outcome of patients in group YM were compared with those in group E. Results: (1) The majority of patients in the two groups were male, but the proportion of male patients in group YM was higher. There was statistically significant difference in gender distribution of patients between the two groups (χ²=18.727, P<0.001). The majority of patients in the two groups were from rural areas, but the proportion of rural patients in group E was higher. There was statistically significant difference in residence distribution of patients between the two groups (χ²=9.306, P=0.002). Patients in group YM mainly had secondary education, while patients in group E mainly had primary education. There was statistically significant difference in distribution of education level of patients between the two groups (χ²=146.797, P<0.001). (2) The most common causes of injury of patients in the two groups were both flame, but the proportion of patients with flame burn injury in group E was higher. There was statistically significant difference in distribution of cause of injury of patients between the two groups (χ²=25.063, P<0.001). The main locations of injury of patients in groups YM and E were respectively public place and private residence. There was statistically significant difference in location distribution of injury of patients between the two groups (χ²=46.313, P<0.001). The main seasons of injury of patients in groups YM and E were respectively summer and winter. There was statistically significant difference in season distribution of patients between the two groups (χ²=23.143, P<0.001). There was statistically significant difference in distribution of total burn area of patients between the two groups (χ²=25.799, P=0.002). The occurrences of full-thickness burn injury of patients in the two groups were similar (χ²=2.685, P=0.101), while there was statistically significant difference in area of full-thickness burn injury of patients between the two groups (χ²=26.702, P=0.002). There was no statistically significant difference in distribution of wound site of patients between the two groups (χ²=3.954, P=0.785). There were no statistically significant differences in incidence and severity distribution of inhalation injury of patients between the two groups (with χ² values respectively 0.425 and 0.672, P values above 0.05). (3) There was statistically significant difference in distribution of admission time of patients between the two groups (χ²=6.632, P=0.036), but there was no statistically significant difference in proportion of delayed resuscitation of patients between the two groups (χ²=1.261, P=0.261). The proportion of escharectomy or tangential excision and skin grafting of patients in group YM was 72.0% (443/615), which was significantly higher than 35.4% (29/82) of group E (χ²=44.498, P<0.001). The incidence of preinjury systemic disease of patients in group YM was 13.2% (81/615), which was significantly lower than 61.0% (50/82) of group E (χ²=108.337, P<0.001). The risk of preinjury systemic disease of patients in group E was 10.30 times of that of patients in group YM [with 95% confidence interval (CI) of 6.24-17.01, P<0.001]. During hospitalization, 59.8% (49/82) of patients in group E suffered from system complications, which was significantly higher than 36.6% (225/615) of group YM (χ²=16.282, P<0.001). The risk of system complication of patients in group E was 2.57 times of patients in group YM (with 95% CI of 1.61-4.12, P<0.001). The length of hospital stay of patients in group E was significantly shorter than that of group YM (U=36 735, P<0.001). There was statistically significant difference in treatment outcome of patients between the two groups (χ²=106.251, P<0.001). The risk of adverse outcome of patients in group E was 7.52 times of group YM (with 95% CI of 4.40-12.88, χ²=67.709, P<0.001). The proportion of abandoning treatment of patients in group E was significantly higher than that of group YM (χ²=150.670, P<0.001). The risk of abandoning treatment of patients in group E was 15.86 times of that of group YM (with 95% CI of 9.36-26.88, P<0.001). There was no statistically significant difference in distribution of reason of abandoning treatment of patients between the two groups (χ²=4.178, P=0.243). Conclusions There were significant differences in the epidemiological characteristics of patients in groups E and YM. In elderly burn patients, the proportion of rural population was higher and the education level was lower. Flame burn was common and burns mostly occurred in private residences and in winter. The total burn area was slightly lower but the area of full-thickness burn injury was larger. The length of hospital stay was shorter and the proportion of surgical treatment was lower. The incidences of preinjury systemic disease and system complication during hospitalization were higher, and therefore the risks of adverse outcome and abandoning treatment were higher.

Objective To investigate the clinical and molecular genetic changes in a Chinese family with oculopha?ryngeal muscular dystrophy(OPMD). Methods We collected the clinical data of the familial members and blood sam?ples from all available 16 familial members, including the proband. The samples were analyzed using modified poly?merase chain reaction amplification and direct sequence analysis. Results Male OPMD patients initially presented with ptosis, followed by pronunciation difficulty, dysphagia and limb weakness whereas female OPMD patients initially pre?sented with swallowing difficulty. Genetic test revealed the abnormal expansions of the GCG trinucleotide repeat from GCG6 to GCG10 in PABPN1 gene in 10 familial members. Conclusions The genetic test and prenatal diagnosis is the key for the prevention treatment of oculopharyngeal muscular dystrophy. The ptosis of eyelid may be the initial symptom for the male patients of oculopharyngeal muscular dystrophy with (GCG)10 mutation.

Conditioned fear and its abnormal extinction are involved in the psychopathology of anxiety disorders, such as posttraumatic stress disorder (PTSD). Cognitive enhancing agents have been demonstrated to alter fear extinction in many animal research literatures. The present review has examined the pharmacological role of gamma-aminobutyric acid (GABA), glutamatergic, cholinergic, adrenergic, dopaminergic, and cannabinoid as well as compounds able to alter the epigenetic and neurotrophic mechanism in fear extinction, highlighting great hope for the future treatment of anxiety disorders with new agents based on the fear extinction.
Animals ; Anxiety Disorders ; drug therapy ; psychology ; Cannabinoids ; pharmacology ; therapeutic use ; Conditioning, Psychological ; drug effects ; Extinction, Psychological ; drug effects ; Fear ; drug effects ; psychology ; Humans ; Nootropic Agents ; pharmacology ; Stress Disorders, Post-Traumatic ; drug therapy ; psychology ; gamma-Aminobutyric Acid ; pharmacology ; therapeutic use

Objective To screen and analyze nucleotide variants in 5'-untranslated region(5'-UTR)in voltage-gated sodium channel α1-subunit gene(SCN1A)in patients with Dravet syndrome and to evaluate the association of the variants with disease.Methods Peripheral blood of 24 patients with Dravet syndrome and 100 unrelated normal persons were collected and genomic DNA was extracted.PCR-sequencing of SCN1 A 5'-UTR in these DNA was performed.To evaluate the possibility of mutation inducing disease,bioinformatics analysis was applied to analyze the conservation of the sequences around the mutation site and predict the potential transcription elements.Results The nucleotide variant of 166.642.520G→A in exon 2 was identified in two patients,but not in normal controls.The mutation was a de novo mutation in a patient with early-onset.In the second proband,the mutation was also carried by his clinically asymptomatic mother.The nucleotide site 166.642.520 was moderately conserved in mammals(62.5%).The average nucleotide identity rate between human and other mammals species in the region adjacent to 166.642.520 was 88.5%.Two potential transcription regulatory elements were predicted on the sequence with the mutation of 166.642.520G>A,and only one on the sequence with wild-type.Conclusions The mutation 166.642.520G>A may be associated with Dravet syndrome and further studied should be performed to verify it and demonstrate its pathogenic mechanisms.