ObjectiveTo investigate the mechanism of Zuogui Wan （ZGW） in improving ovarian inflammatory microenvironment and stemness of ovarian germline stem cells （OSCs） for treating ovarian aging via the cyclic guanosine monophosphate/adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsForty C57BL/6 female mice were randomly divided into a blank group， a model group， a low-dose ZGW group （2.7 g·kg^-1）， a high-dose ZGW group （5.4 g·kg^-1）， and an estradiol valerate group （0.15 mg·kg^-1）， with 8 mice in each group. Except the blank group， all other groups received a single intraperitoneal injection of cyclophosphamide at 120 mg·kg^-1 to establish an ovarian aging mouse model. After successful modeling， each group was continuously administered for 4 weeks， once daily. The physiological status of the mice was observed， and the ovarian index was calculated. The estrus cycle of the mice was monitored. Hematoxylin-eosin （HE） staining was used to observe pathological changes in ovarian tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum sex hormone levels. Serum inflammatory factors interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and mouse interleukin-6 （IL-6） levels were detected using kits. Western blot was used to detect the protein expression of ovarian cGAS， STING， p-STING， TANK-binding kinase 1 （TBK1）， p-TBK1， interferon-induced transmembrane protein 3 （Fragilis）， and Vasa homolog protein （MVH）. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors in ovarian tissue. Immunofluorescence double labeling was performed to locate OSCs in ovarian tissues， and fluorescence intensities of OSCs markers MVH and octamer binding transcription factor 4 （Oct4） were calculated. ResultsCompared with the blank group， the model group showed reduced body weight， ovarian wet weight， and ovarian index （P<0.01） and a disordered estrus cycle （P<0.01）. In addition， the levels of serum follicle-stimulating hormone （FSH）， TNF-α， IL-6， and IL-1β were increased （P<0.01）， while anti-Müllerian hormone （AMH） and estradiol （E₂） levels were decreased （P<0.01）. The protein expression of cGAS， p-STING/STING， and p-TBK1/TBK1 in ovarian tissue was increased （P<0.05， P<0.01）， while that of OSCs stemness factors MVH and Fragilis was reduced （P<0.01）. Immunofluorescence indicated a reduction in MVH and Oct4 expression in OSCs （P<0.01）. The mRNA expression of inflammatory factors TNF-α， IL-6， and IL-1β in ovarian tissue was increased （P<0.05， P<0.01）. Compared with the model group， the treatment groups exhibited improved body weight， ovarian wet weight， and ovarian index （P<0.05） and a reduced rate of estrus cycle disorder （P<0.05， P<0.01）. The levels of serum FSH， TNF-α， IL-6， and IL-1β were decreased （P<0.05， P<0.01）， while AMH and E₂ levels were increased （P<0.01）. The protein expression levels of cGAS， p-STING/STING， and p-TBK1/TBK1 in ovarian tissue were decreased （P<0.05）， while the protein expression of MVH and Fragilis was increased （P<0.05）， and the fluorescence intensities of MVH and Oct4 were increased （P<0.05， P<0.01）. The mRNA expression of inflammatory factors in ovarian tissue was decreased （P<0.05）. ConclusionZGW alleviate ovarian inflammatory response， regulate ovarian microenvironment homeostasis， and maintain stemness of OSCs in ovarian aging mice probably by modulating the cGAS-STING signaling pathway， thereby improving ovarian function and delaying ovarian aging.

Huangqintang， with its accurate efficacy， is a classic formula specialized in treating dysentery recommended and promoted by medical experts from successive generations， and it was included in the Catalogue of Ancient Classic Prescriptions （the Second Batch， Han Chinese medicine prescriptions） published by the National Administration of Traditional Chinses Medicine （TCM） in 2023. The method of bibliometrics was applied in this study to conduct textual research on the classic formula Huangqintang and provide a literature reference for the development of modern preparations of Huangqintang. A total of 2 026 pieces of ancient literature were searched with "Huangqintang" as the key word， and 23 pieces of effective data were selected， involving 15 ancient TCM books. The historic evolution， composition， dosage， origin， processing methods， preparation and decocting methods， efficiency， and application of Huangqintang were carefully reviewed. The results showed that Huangqintang was first recorded in the Treatise on Febrile Diseases written by ZHANG Zhongjing. It has the effect of clearing heat， stopping dysentery， regulating the middle， and downbearing counterflow and has become one of the classic formulas widely used in clinical practice. Because of its accurate efficacy， medical experts from later generations have modified it from its original composition. Though many prescriptions have different names， it is the manifestation of physicians' inheritance and development of the thought of ZHANG Zhongjing. Ancient literature showed this prescription had wide indications yet centered on digestive system diseases such as dysentery and abdominal pain. Modern applications of Huangqintang involve digestive， respiratory， ophthalmology and otolaryngology， gynecological， skin， musculoskeletal system， and connective tissue， and this prescription has great potential in treating ulcerative colitis， diarrhea， acute enteritis， and damp-heat dysentery. Through a systematic textual excavation and review of the ancient literature about Huangqintang， the paper has confirmed its key information， so as to provide a scientific basis for the clinical application and new drug development of classic formulas.

Objective To systematically evaluate the risk prediction models for anastomotic leakage (AL) in patients with esophageal cancer after surgery. Methods A computer-based search of PubMed, EMbase, Web of Science, Cochrane Library, Chinese Medical Journal Full-text Database, VIP, Wanfang, SinoMed and CNKI was conducted to collect studies on postoperative AL risk prediction model for esophageal cancer from their inception to October 1st, 2023. PROBAST tool was employed to evaluate the bias risk and applicability of the model, and Stata 15 software was utilized for meta-analysis. Results A total of 19 literatures were included covering 25 AL risk prediction models and 7373 patients. The area under the receiver operating characteristic curve (AUC) was 0.670-0.960. Among them, 23 prediction models had a good prediction performance (AUC>0.7); 13 models were tested for calibration of the model; 1 model was externally validated, and 10 models were internally validated. Meta-analysis showed that hypoproteinemia (OR=9.362), postoperative pulmonary complications (OR=7.427), poor incision healing (OR=5.330), anastomosis type (OR=2.965), preoperative history of thoracoabdominal surgery (OR=3.181), preoperative diabetes mellitus (OR=2.445), preoperative cardiovascular disease (OR=3.260), preoperative neoadjuvant therapy (OR=2.977), preoperative respiratory disease (OR=4.744), surgery method (OR=4.312), American Society of Anesthesiologists score (OR=2.424) were predictors for AL after esophageal cancer surgery. Conclusion At present, the prediction model of AL risk in patients with esophageal cancer after surgery is in the development stage, and the overall research quality needs to be improved.

BACKGROUND:Intestinal acute graft-versus-host disease is one of the most aggressive complications after allogeneic hematopoietic stem cell transplantation with high lethality.How to improve intestinal inflammation and regulate autophagy by applying traditional Chinese medicine in order to treat intestinal acute graft-versus-host disease is a worthwhile research issue nowadays. OBJECTIVE:To investigate the mechanism of Huangqintang modulating intestinal flora for the treatment of intestinal acute graft-versus-host disease. METHODS:CB6F1 mice were irradiated with 60Co X radiation at a total dose of 8 Gy,and then single nucleated cell suspensions(bone marrow cells+splenocytes)from Balb/c H-2d mice were injected into the tail vein in order to prepare a model of intestinal acute graft-versus-host disease.These samples were randomly divided into the model group and the high-,moderate-,and low-dose Huangqintang groups.After modeling,the model,high-,moderate-,and low-dose groups received different doses of Huangqintang or an equal volume of saline by continuous gavage for 14 days.Clinical acute graft-versus-host disease grading,and survival time was recorded.Small intestinal tissues from each group were stained with hematoxylin and eosin for small intestinal mucosal pathology scoring.The intestinal flora of mice in each group was detected using 16S rDNA sequencing.Autophagy-related markers were detected using immunofluorescence,immunohistochemistry,and PCR. RESULTS AND CONCLUSION:(1)Compared with the model group,the survival time of mice was significantly prolonged(P<0.01);the clinical acute graft-versus-host disease scores were significantly reduced(P<0.01);the pathological grading scores of the small intestinal mucosa were significantly diminished(P<0.01);the levels of the small intestinal tissue inflammatory factors tumor necrosis factor-α,interleukin-1β,and interleukin-6,were significantly decreased(P<0.01);the structural integrity of the small intestinal mucosal epithelium was partially restored in mice after the intervention of moderate and high-dose Huangqintang.(2)The study of intestinal flora found that compared with the model group,the pro-inflammatory strain Enterococcus was significantly reduced(P<0.05),while beneficial bacteria such as Clostridium_innocuum and Rhodococcus,a pro-autophagy bacterium,were significantly elevated(P<0.05)in the moderate-dose Huangqintang group.(3)Compared with the model group,the autophagy markers were significantly elevated in the moderate-dose Huangqintang group(P<0.05);under transmission electron microscopy,the number of autophagic vacuoles of moderate-dose Huangqintang group increased significantly.(4)The results showed that Huangqintang significantly reduced the abundance of conditionally pathogenic bacteria and the level of inflammatory factors in small intestinal tissues,and increased the relative abundance of beneficial bacteria and promoted the expression of autophagy in the small intestinal mucosa,which resulted in a significant improvement of intestinal symptoms in mice with acute graft-versus-host disease.

OBJECTIVE: To explore the clinical features and management of a child with Chitayat syndrome. METHODS: A child presented at the Fengqing People's Hospital on August 8 2019 was selected as the study subject. Clinical data of the child were retrospectively analyzed. Peripheral blood samples were collected from the child and his father and sister. Whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genome Browser, AlphaFold, and PolyPhen-2 were employed for protein structure simulation and amino acid sequence conservation analysis. Pathogenicity of the variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Literature was retrieved from databases including CNKI, Wanfang, and PubMed using the keyword "Chitayat syndrome". The clinical characteristics and prognosis of patients with Chitayat syndrome were reviewed and analyzed. This study was approved by the Ethics Committee the Seventh Affiliated Hospital of Sun Yat-sen University (Ethics No.: KY-2024-086-01). RESULTS: The child was born at full term and had special facial features, skeletal abnormalities, recurrent respiratory tract infections and global developmental delay. WES and Sanger sequencing revealed that he has harbored a heterozygous c.266A>G p.(Tyr89Cys) variant of the ERF gene. Protein structure modeling suggested that the mutant protein has increased spatial distance between the side chain group and DNA, which may reduce its binding affinity to DNA. Amino acid sequence analysis indicated that the p.Tyr89 residue is highly conserved across multiple species. The variant was therefore classified as pathogenic (PM1+PM2_Supporting+PM6+PS1+PP3). The patient was diagnosed with "Chitayat syndrome". Nutritional support and rehabilitation training were recommended, though the child had died of severe pneumonia at 13 months old. Literature retrieval has collected 7 relevant articles, which involved 14 cases of Chitayat syndrome confirmed by genetic testing. Together with our case, all patients had facial dysmorphisms and skeletal deformities. Fourteen patients (93.3%) had respiratory distress. Seven of them (46.7%) had recurrent respiratory infections and 7 (46.7%) were confirmed with respiratory tract malacia. Eight (53.3%) patients had neuropsychological retardation, while 8 (53.3%) had growth delay. The main interventions for Chitayat syndrome include respiratory and nutritional support, and rehabilitation training for developmental delays. CONCLUSION Chitayat syndrome is rarely seen and its clinical manifestations may vary. Airway management and early intervention of developmental delay are important for improving the prognosis.
Humans ; Male ; Exome Sequencing ; Female ; Mutation ; Child, Preschool ; Infant ; Developmental Disabilities/genetics*

Lung transplantation is an important means to treat end-stage lung disease and improve the survival rate and quality of life of patients. However, many postoperative complications seriously affect the prognosis of recipients. Accurate identification of key prognostic factors and construction of individualized and accurate prediction models are of great significance for postoperative prognosis evaluation, treatment strategy formulation and clinical decision-making. In recent years, the clinical prediction model of lung transplantation has gradually changed from traditional statistical methods to machine learning-driven. Compared with traditional models such as Cox regression and Logistic regression, machine learning models such as random forest, support vector machine and artificial neural network have certain advantages in postoperative survival rate prediction, early warning of complications and pulmonary function evaluation. However, their application is also affected by insufficient sample size and poor interpretability of models. Under the condition of small samples, the traditional model still has important value in prediction accuracy. The appropriate prediction model should be selected according to the clinical status of lung transplantation in China, considering the factors such as sample size, variable complexity and model interpretability. In the future, a multi-center, large-sample lung transplantation database should be constructed to further optimize and tap the potential of machine learning algorithms to improve the robustness and clinical applicability of the model.

Objective:To evaluate the efficacy and safety of combining third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) with brain radiotherapy in patients with newly diagnosed EGFR mutation-positive non-small cell lung cancer (NSCLC) with brain metastases. Methods:A retrospective analysis was performed on the clinical data of patients with newly diagnosed EGFR-mutant NSCLC with brain metastases who received first-line treatment with third-generation EGFR-TKI with or without brain radiotherapy at the Fourth Affiliated Hospital of Guangxi Medical University between January 2018 and December 2022. Patients treated with EGFR-TKI plus brain radiotherapy were assigned to the combination group, while those treated with EGFR-TKI alone were assigned to the monotherapy group. Intracranial progression-free survival (iPFS), progression-free survival (PFS), overall survival (OS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and adverse events were compared between groups. Subgroup analyses were performed according to EGFR exon 19 deletion (19del) and exon 21L858R mutation status. Survival was estimated using the Kaplan-Meier method, with the log-rank test applied for group comparisons and univariate analysis, while multivariate analysis was conducted using Cox proportional hazards regression model. Results:A total of 107 patients were included: 57 (53%) in the monotherapy group and 50 (47%) in the combination group. The combination therapy significantly improved iORR (80% vs. 60%, P=0.023), prolonged median OS (37.7 vs. 31.6 months, P=0.004), and extended median iPFS (21.8 vs. 16.7 months, P=0.018). The iDCR was 100% in both groups, and the difference in median PFS was not statistically significant (18.6 vs. 15.2 months, P=0.086). In the 19del subgroup ( n=53), patients in the combination group had longer OS ( P=0.028) and iPFS ( P=0.028). In the 21L858R subgroup ( n=54), the median OS was also longer in the combination group ( P=0.050). Multivariate analysis identified TKI monotherapy and an Eastern Cooperative Oncology Group (ECOG) performance status score=2 as independent adverse prognostic factors for iPFS, while TKI monotherapy, age ≥65 years, ECOG score=2, and >3 brain metastases were the independent adverse prognostic factors for OS. The incidence of adverse events did not differ significantly between groups (all P>0.05). Conclusions:First-line combination therapy with third-generation EGFR-TKI and cranial radiotherapy provides superior efficacy and acceptable safety compared with EGFR-TKI monotherapy in patients with EGFR-mutant lung adenocarcinoma and brain metastases. Both EGFR 19del and 21L858R mutation subgroups benefit from the combined treatment approach.

In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.

Objective Compare the depression phenotypes of a breast cancer tumor-bearing mouse model constructed using two different method and a mouse model of breast cancer depression with clinical manifestations,as well as assess their suitability for basic research.Methods We constructed a tumor model with 4T1 breast cancer cells alone(4T1 group)and a tumor-depression composite model given chronic unpredictable mild(CUMS)(4T1+CUMS group).The experimental period was 42 d,and the body mass,tumor volume,and survival time of the mice were monitored throughout the whole process.Two depressive behavioral tests(of sucrose preference test,open field test,tail suspension test,and elevated plus maze)were performed on the 15th and 29th days,respectively.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of hippocampal neurons in brain tissue sections.Results(1)Body mass:The body mass of the 4T1 group and 4T1+CUMS group began to decrease from 29 d,and the body mass of the 4T1+CUMS group was significantly lower than that of the 4T1 group and Control group at the end of the experiment(P<0.001).(2)Tumor volume:There was no significant difference in the growth rate of tumors between the two model groups throughout the experiment(P>0.05).(3)Survival time:The survival rates of the 4T1 group and 4T1+CUMS group were 100％and 60％,and the first death of mice in the 4T1+CUMS group was on the 36th day.(4)Behavior test of depression:There was no significant difference between the three groups in the first depressive behavior tests(P>0.05),and the two groups showed obvious depressive phenotypes in the second behavioral tests.The sucrose preference index and activity distance in the central area were significantly decreased in the two model groups(P<0.001),and the immobility time was significantly increased(P<0.001).(5)Pathological section of brain tissue:On pathological examination of brain tissue,we observed a reduced number of neuronal cells in the hippocampus of the 4T1 group and 4T1+CUMS group,their morphology was irregular,the arrangement between the cells was disordered and the gap was unclear,and some nucleoli were blurred.Conclusions Although the tumor-only method and the tumor with compound stress stimulation method can both be used to prepare breast cancer depression models,the tumor-only modeling method is simpler and the mortality rate after successful modeling is higher.The long window of time is convenient for subsequent drug administration and detection,and the causes of the depression phenotype are more in line with the clinical causes and manifestations.Therefore,the 4T1 model can provide a reference model for future animal experiments on breast cancer tumor-related depression.

Objective:To explore the association between pre-diabetes and glomerular hyperfiltration status in residents in China.Methods:The study subjects were the non-diabetes population in China Chronic Disease and Risk Factor Surveillance in 2018. According to the definition of prediabetes, the study subjects were divided into normoglycemic and pre-diabetes groups, and multivariate factorial logistic regression model was used to analyze the association between prediabetes and the risk for glomerular hyperfiltration and glomerular filtration rate decline, respectively. Restricted cubic spline was used to explore the dose-response relationship between different glycemic indexes and the risk for glomerular hyperfiltration.Results:A total of 129 735 eligible study subjects aged 18 to 74 years were included, including 45 336 persons with prediabetes. After adjusting for confounders, the OR for glomerular hyperfiltration in the prediabetes group was 1.26 (95% CI: 1.20-1.32) compared with the normoglycemic group, and prediabetes was not associated with decreased glomerular filtration rate ( OR=1.03, 95% CI: 0.96-1.12). Age-stratified results showed a 28% increase of risk for glomerular hyperfiltration in prediabetes group compared with normoglycemic group in those aged 18-59 year ( OR=1.28, 95% CI: 1.21-1.35), and a 15% increase of risk in old adults aged 60-74 years ( OR=1.15, 95% CI: 1.05-1.25); the risk for glomerular hyperfiltration in women with prediabetes ( OR=1.38, 95% CI: 1.29-1.47) was higher than that in men with prediabetes ( OR=1.14, 95% CI: 1.06-1.22); and the risk for prediabetes glomerular hyperfiltration was higher in those with insufficient physical activity ( OR=1.29, 95% CI: 1.22-1.36) than in those who were physically active ( OR=1.16, 95% CI: 1.04-1.29). Restricted cubic spline results showed that fasting plasma glucose, glycosylated hemoglobin and glomerular hyperfiltration risk all showed U-shaped associations, and 2 hours blood glucose glomerular hyperfiltration risk after taking sugar showed an approximate J-shaped association. Conclusions:The risk for glomerular hyperfiltration exists in the prediabetes population, and prediabetes is not associated with the decrease in glomerular filtration rate. Hyperglycemia control at an early and reversible stage is important to prevent glomerular hyperfiltration developing to hypofiltration and renal impairment.