Objective:To analyze the clinical features and genetic characteristics of a patient with Shwachman-Diamond syndrome (SDS) due to compound heterozygous variants of SBDS gene.Methods:A female child with SDS who was admitted to the Children's Hospital Affiliated to Zhengzhou University in February 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her elder sister and parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a 1-year-and-1-month-old girl, had mainly manifested with diarrhea, hematochezia, growth retardation and malnutrition, along with increased transaminases and decreased neutrophils and hemoglobin. The anteroposterior X-ray of her left wrist indicated significantly delayed bone age. Colonoscopy revealed that her colorectal mucosa was erosive with oily food residues attached to the intestinal lumen. Genetic testing revealed that she has harbored c. 258+ 2T>C and c. 100A>G compound heterozygous variants of the SBDS gene. The c. 258+ 2T>C variant has derived from her father and known to be pathogenic, whilst the other has derived from her mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 100A>G variant was classified as likely pathogenic (PM1+ PM2_Supporting+ PM3+ PM5+ PP3). Conclusion:The compound heterozygous variants of c. 258+ 2T>C and c. 100A>G probably underlay the SDS in this child. For children with refractory diarrhea, liver damage and growth retardation, SDS should be suspected, and genetic testing can facilitate the diagnosis and treatment.

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 expression of serum miR-133a-3p and miR-324-3p in patients with persistent atrial fibrillation and their relationship with recurrence of atrial fibrillation after radiofrequency ablation.Methods A total of 180 patients with persistent atrial fibrillation(persistent atrial fibrillation group)who were hospitalized in Cangzhou City People's Hospital from July 2019 to July 2022 and received radiofrequency ablation were collected as research objects.According to whether atrial fibrillation recurred,they were assigned into a non recurrence group(n=116)and a recurrence group(n=64).Meanwhile,another 180 healthy individuals who underwent physical examination at the hospital were regarded as the control group.The expression levels of serum miR-133a-3p and miR-324-3p of each group were compared.Multivariate Logistic regression was applied to analyze the factors influencing the recurrence of persistent atrial fibrillation after radiofrequency ablation,and ROC curve analysis was applied to analyze the predictive value of serum miR-133a-3p and miR-324-3p levels for the recurrence of atrial fibrillation in patients with persistent atrial fibrillation after radiofrequency ablation.Results Compared with the control group,the levels of serum miR-133a-3p(0.76±0.25)and miR-324-3p(0.68±0.21)in the persistent atrial fibrillation group were lower than the control group(1.03±0.32,1.05±0.30),and the differences were statistically significant(t=8.921,13.556,all P<0.05).The serum levels of miR-133a-3p(0.58±0.19)and miR-324-3p(0.50±0.16)in the recurrent group were obviously lower than those in the non recurrent group(0.86±0.27,0.78±0.25),and the differences were statistically significant(t=7.349,8.087,all P<0.05).Multivariate Logistic regression analysis showed that serum miR-133a-3p[OR(95%CI):0.673(0.534～0.848)]and miR-324-3p[OR(95%CI):0.756(0.629～0.909)]were protective factors for atrial fibrillation recurrence after radiofrequency ablation in patients with persistent atrial fibrillation,while heart rate[OR(95%CI):2.143(1.265～3.631)]and LAD[OR(95%CI):1.756(1.159～2.661)]were independent risk factors for atrial fibrillation recurrence after radiofrequency ablation in patients with persistent atrial fibrillation(all P<0.05).The AUC of the combination of miR-133a-3p and miR-324-3p in predicting atrial fibrillation recurrence after radiofrequency ablation in patients with persistent atrial fibrillation was 0.901,with the sensitivity and specificity were 82.81%and 86.21%,respectively,which was better than those of their respective prediction alone(Z=4.210,2.804,all P<0.05).Conclusion The expressions of serum miR-133a-3p and miR-324-3p in patients with persistent atrial fibrillation are reduced,and the combination of the two has a good reference value in predicting the recurrence of atrial fibrillation in patients with persistent atrial fibrillation after radiofrequency ablation.

Objective:To analyze the general chapter for lotions 0127 of the Chinese Pharmacopoeia 2020 Vol-ume Ⅳ,and discuss how to improve the general technical requirements of lotions 0127 in the Chinese Pharma-copoeia.Methods:By comparing the general chapter for lotions in domestic and international pharmacopoe-ias,the definition,classification,process,storage and corresponding inspection requirements were analyzed.Results and Conclusions:The general chapter for lotions 0127 of the Chinese Pharmacopoeia should be revised,including improvement of the definition,increasement of forms of preparations,and expansion of included varieties,so as to promote scientific regulation for drugs and exhibit a guiding role of the Chinese pharmacopoeia in drug control.

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.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*

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

【Objective】 To explore the role and value of applied muscle tension (AMT) in preventing vasovagal nerve reaction (VVR) in blood donors. 【Methods】 A total of 2 992 people, susceptible to suffer VVR from May 2020 to may 2022, were randomly divided into control group (1406 cases) and observation group (1 586 cases). The control group was not given AMT intervention, while the observation group received AMT intervention at different periods during blood donation. The changes of systolic blood pressure, diastolic blood pressure, heart rate and psychological state of anxiety (self-rating anxiety scale, SAS) of blood donors were monitored in the two groups at each period to compare the occurrence of VVR. 【Results】 There were no statistically significant differences in blood pressure and heart rate between the two groups before blood donation (P>0.05). The parameters were relatively stable in observation group during and after donation, but significantly different from that of the controls(P>0.05). SAS score was similar in two groups before blood donation(P>0.05), while decreased in observation group during and after donation in comparison with the controls(P<0.05). The incidence of VVR in the observation group was 3.09%, which was significantly lower than that in the control group (7.97%)(P<0.05). The incidence of VVR was 2.18% after AMT exercise during blood donation. 【Conclusion】 AMT intervention in different periods of blood donation can significantly reduce the occurrence of VVR.

Objective:To investigate the clinical characteristics, endoscopic features and management of acquired tracheoesophageal fistula (TEF) by esophageal foreign bodies in children.Methods:The clinical data and follow-up data of 21 children with acquired TEF who were treated in Children′s Hospital Affiliated to Zhengzhou University from January 2008 to January 2019 were retrospectively analyzed.Results:A total of 21 cases with esophageal foreign bodies were button batteries, irregular iron sheets, game coins, jujube seed, animal bone sheets, and fish thorn.The statistical results suggested that the cases of button batteries were 7 cases (33.33%), 4 cases of jujube pit (19.05%), 3 cases of irregular iron (14.29%) and 3 cases of animal bone (14.29%), 2 cases of game coin (9.52%), 2 cases of fish thorn (9.52%). All foreign bodies were removed by endoscopy.Esophageal perforation with TEF was discovered in 17 cases (80.95%) during the operation.Esophageal perforation with TEF was found in 4 cases (19.05%) within 2 week after the operation, and no death occurred.A total of 13 case fistula size ≤5 mm (61.90%), 4 case fistula size>5 mm and ≤10 mm (19.05%) and 4 case fistula size >10 mm (19.05%). The treatment methods included gastrointestinal decompression and nasojejunal nutrition tube support in 10 cases (47.61%), gastrostomy and jejunostomy in 4 cases (19.05%), surgical repair in 4 cases (19.05%) and endoscopic titanium clip suture in 3 cases (14.29%). Five cases (23.81%) were healed in 3 months, 6 cases (28.57%) in 5 months, 4 cases (19.05%) in 8 months, and 2 cases (9.52%) in 12 months.Conclusions:Acquired TEF in children are mostly caused by special foreign bodies embedded in the esophagus, and endoscopic management is effective for fistulas with less trauma.Appropriate operation and intervention should be taken as early as possible.

Objective:To analyze the clinical characteristics, endoscopic manifestations, complications and related risk factors of button battery ingestion in 58 children, thus providing the basis for clinical diagnosis and treatment.Methods:The medical data of 58 children with button battery ingestion were collected and researched at Children′s Hospital Affiliated to Zhengzhou University from September 2015 to September 2020.The demographic information, battery impaction location, duration, symptoms, mucosal injury level, battery size, treatment, complications and follow-up results were analyzed.Results:The average age of the patients with button battery ingestion was (25.7±15.4)months, including 40 boys(68.9%). The average retention time of the battery in digestive tract was 13.8(2, 96) h. Vomiting, salivation, dysphagia, cough and fever were the common chief complaints.There were 29(50.0%) cases of grade I mucosal injury, as well as 14(24.1%) cases, 10(17.2%) cases and 10(17.2%) cases for grade Ⅱ, grade Ⅲ and grade Ⅳ, respectively.Additionally, common complications included esophageal stenosis, esophageal perforation and esophageal-tracheal fistula.Logistic regression analysis showed that location(esophagus) and diameter(≥15 mm) of battery incarceration were important predictors of complications.Conclusion:The degree of mucosal damage is associated with the diameter and impaction location of battery.The button battery embedded in the esophagus is prone to complications, while the ones retained in the stomach were not vulnerable to serious complications.Endoscopy and other related examinations should be performed again in 1 to 3 weeks after the button removal to determine the outcome of complications and to intervene in time.