Objective:To screen the key genetic,diagnostic and therapeutic targets of chronic obstructive pulmonary disease(COPD)patients by using microarray datasets and Mendelian randomization(MR)method,and to provide the evidence for clinical diagnosis and treatment of COPD.Methods:Four COPD gene expression profile datasets were obtained from the Gene Expression Omnibus(GEO)database.The data were processed and normalized using R software,and differentially expressed genes(DEGs)were screened.MR analysis was performed to explore the causal relationship between COPD and expression quantitative trait loci(eQTL),intersection with DEGs was taken to identify potential key targets.Gene Set Enrichment Analysis(GSEA),Gene Ontology(GO)functional enrichment analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were conducted to investigate the functional roles and pathways of the key targets,external datasets were used to validate their expression.Results:A total of 1 571 DEGs were screened,including 820 upregulated genes and 751 downregulated genes.MR analysis identified 286 COPD-related genes,and intersection with DEGs revealed 3 upregulated genes:diacylglycerol kinase gamma(DGKG),neurofilament heavy polypeptide(NEFH),and Fc receptor like B(FCRLB);and 6 downregulated genes:STEAP4 metalloreductase(STEAP4),pleckstrin homology domain containing family F member 2(PLEKHF2),CD3d molecule(CD3D),transgelin 2(TAGLN2),tripartite motif containing 22(TRIM22),and ribosomal protein L9(RPL9).The biological function analysis results indicated that these genes were mainly involved in pathways such as iron ion transport into the cells,oxidoreductase activity,primary immunodeficiency,and Th1 and Th2 cell differentiation.The MR analysis results confirmed the causal relationship between these targets and COPD.The external validation results showed that compared with healthy controls,the expression level of FCRLB in COPD samples was significantly increased(P<0.01),while the expression levels of CD3D and RPL9 were significantly decreased(P<0.05 or P<0.01),which was consistent with the MR analysis results,highlighting the reliability of this study.Conclusion:DGKG,NEFH,FCRLB,STEAP4,PLEKHF2,CD3D,TAGLN2,TRIM22,and RPL9 may serve as important regulatory factors and clinical diagnostic/therapeutic targets in the pathogenesis of COPD,providing clues for early screening,diagnosis,and targeted treatment of COPD.

Objective:To construct and validate a prognostic prediction model for patients with ovarian metastases from colorectal cancer after radical resection.Methods:A retrospective case series analysis was conducted on the clinical and pathological data of 81 patients with colorectal cancer and ovarian metastases who underwent radical resection for ovarian metastases at the Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, between January 2014 and December 2023. The patients were all female, with an age ( M(IQR)) of 49(13) years (range: 22 to 79 years). The primary tumor was located in the colon in 60 cases (74.1%) and in the rectum in 21 cases (25.9%). Univariate and multivariate Cox regression analyses were used to identify independent risk factors affecting prognosis. A risk scoring system was constructed, and patients were assigned to high-risk and low-risk groups based on their risk scores. The predictive performance of the scoring system was assessed, and 5-fold cross-validation was performed to evaluate the model′s stability on the internal dataset. Results:Among the 81 patients with ovarian metastases, a high proportion had T4 stage (58 cases, 71.6%), lymph node positivity (68 cases, 84.0%), and colon cancer (60 cases, 74.1%). Preoperative imaging suggested unilateral ovarian metastasis in 15 patients (23.4%), but pathological examination after bilateral oophorectomy confirmed bilateral ovarian metastases. Among the 17 patients who initially underwent unilateral oophorectomy, 11 developed contralateral ovarian metastases at varying times postoperatively. Univariate Cox proportional hazards regression analysis revealed that positive lymph node ratio ( HR=2.68,95% CI:1.41 to 5.09, P=0.003), N stage ( HR=2.07,95% CI:1.08 to 3.95, P=0.028),maximum diameter of metastatic tumors ( HR=2.27,95% CI:1.04 to 4.96, P=0.040),and peritoneal metastasis or ascites at the time of ovarian metastasis ( HR=2.04,95% CI:1.02 to 4.08, P=0.043) were significantly associated with overall survival in patients with ovarian metastasis from colorectal cancer. Multivariate regression analysis identified that positive lymph node ratio ( HR=3.34,95% CI:1.08 to 10.34, P=0.037) and maximum diameter of metastatic tumors ( HR=2.65,95% CI:1.19 to 5.88, P=0.017) were independent prognostic factors for overall survival following radical oophorectomy in patients with ovarian metastasis from colorectal cancer. Based on the regression coefficients from the multivariate analysis for variables (ovarian metastatic tumor diameter ≥6 cm, positive lymph node ratio ≥0.3,and presence of peritoneal metastasis or ascites), a risk scoring system was developed. Using the optimal cutoff value (154 points) for the risk score,patients were divided into high-risk (19 cases) and low-risk (62 cases) groups. Kaplan-Meier survival curves demonstrated that the high-risk group had significantly lower median overall survival (27 months) and median disease-free survival (22 months) compared to the low-risk group (median overall survival 90 months,median disease-free survival not reached; both P<0.01). Receiver operating characteristic curve analysis showed that the area under the curve(AUC) for predicting 1-,3-,and 5-year overall survival was 0.731(95% CI:0.563 to 0.899), 0.703(95% CI:0.573 to 0.833), and 0.776(95% CI: 0.657 to 0.894), respectively. The AUC for predicting 1-,3-, and 5-year disease-free survival was 0.724(95% CI:0.397 to 0.993),0.710(95% CI:0.514 to 0.906),and 0.688(95% CI:0.478 to 0.898),respectively,indicating good performance of the model.The decision curve analysis showed that the model has good clinical net benefit and the results of the 5-fold cross-validation showed that the model demonstrated stability in the internal dataset. Conclusions:When performing radical resection for ovarian metastasis from colorectal cancer,bilateral oophorectomy should be considered to minimize the risk of postoperative recurrence. Patients with ovarian metastasis from colorectal cancer,characterized by a metastatic tumor diameter ≥6 cm,a positive lymph node ratio ≥0.3,and the presence of peritoneal metastasis or ascites, tend to have a poorer prognosis. Based on these findings,a clinical prognostic scoring system for radical resection of ovarian metastasis from colorectal cancer has been developed to stratify patients into different risk groups and may assist in postoperative risk assessment and management.

Objective:To construct and validate a prognostic prediction model for patients with ovarian metastases from colorectal cancer after radical resection.Methods:A retrospective case series analysis was conducted on the clinical and pathological data of 81 patients with colorectal cancer and ovarian metastases who underwent radical resection for ovarian metastases at the Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, between January 2014 and December 2023. The patients were all female, with an age ( M(IQR)) of 49(13) years (range: 22 to 79 years). The primary tumor was located in the colon in 60 cases (74.1%) and in the rectum in 21 cases (25.9%). Univariate and multivariate Cox regression analyses were used to identify independent risk factors affecting prognosis. A risk scoring system was constructed, and patients were assigned to high-risk and low-risk groups based on their risk scores. The predictive performance of the scoring system was assessed, and 5-fold cross-validation was performed to evaluate the model′s stability on the internal dataset. Results:Among the 81 patients with ovarian metastases, a high proportion had T4 stage (58 cases, 71.6%), lymph node positivity (68 cases, 84.0%), and colon cancer (60 cases, 74.1%). Preoperative imaging suggested unilateral ovarian metastasis in 15 patients (23.4%), but pathological examination after bilateral oophorectomy confirmed bilateral ovarian metastases. Among the 17 patients who initially underwent unilateral oophorectomy, 11 developed contralateral ovarian metastases at varying times postoperatively. Univariate Cox proportional hazards regression analysis revealed that positive lymph node ratio ( HR=2.68,95% CI:1.41 to 5.09, P=0.003), N stage ( HR=2.07,95% CI:1.08 to 3.95, P=0.028),maximum diameter of metastatic tumors ( HR=2.27,95% CI:1.04 to 4.96, P=0.040),and peritoneal metastasis or ascites at the time of ovarian metastasis ( HR=2.04,95% CI:1.02 to 4.08, P=0.043) were significantly associated with overall survival in patients with ovarian metastasis from colorectal cancer. Multivariate regression analysis identified that positive lymph node ratio ( HR=3.34,95% CI:1.08 to 10.34, P=0.037) and maximum diameter of metastatic tumors ( HR=2.65,95% CI:1.19 to 5.88, P=0.017) were independent prognostic factors for overall survival following radical oophorectomy in patients with ovarian metastasis from colorectal cancer. Based on the regression coefficients from the multivariate analysis for variables (ovarian metastatic tumor diameter ≥6 cm, positive lymph node ratio ≥0.3,and presence of peritoneal metastasis or ascites), a risk scoring system was developed. Using the optimal cutoff value (154 points) for the risk score,patients were divided into high-risk (19 cases) and low-risk (62 cases) groups. Kaplan-Meier survival curves demonstrated that the high-risk group had significantly lower median overall survival (27 months) and median disease-free survival (22 months) compared to the low-risk group (median overall survival 90 months,median disease-free survival not reached; both P<0.01). Receiver operating characteristic curve analysis showed that the area under the curve(AUC) for predicting 1-,3-,and 5-year overall survival was 0.731(95% CI:0.563 to 0.899), 0.703(95% CI:0.573 to 0.833), and 0.776(95% CI: 0.657 to 0.894), respectively. The AUC for predicting 1-,3-, and 5-year disease-free survival was 0.724(95% CI:0.397 to 0.993),0.710(95% CI:0.514 to 0.906),and 0.688(95% CI:0.478 to 0.898),respectively,indicating good performance of the model.The decision curve analysis showed that the model has good clinical net benefit and the results of the 5-fold cross-validation showed that the model demonstrated stability in the internal dataset. Conclusions:When performing radical resection for ovarian metastasis from colorectal cancer,bilateral oophorectomy should be considered to minimize the risk of postoperative recurrence. Patients with ovarian metastasis from colorectal cancer,characterized by a metastatic tumor diameter ≥6 cm,a positive lymph node ratio ≥0.3,and the presence of peritoneal metastasis or ascites, tend to have a poorer prognosis. Based on these findings,a clinical prognostic scoring system for radical resection of ovarian metastasis from colorectal cancer has been developed to stratify patients into different risk groups and may assist in postoperative risk assessment and management.

[Objective] To explore the expression of Nectin-4 in invasive bladder urothelial carcinoma (BUC) tissue and its clinical significance, so as to provide reference for clinical diagnosis and treatment of BUC. [Methods] Nectin-4 expression in 60 cases of invasive BUC and 40 cases of chronic inflammation of bladder mucosa was detected with immunohistochemical staining (IHC) and RNAscope.The results of the two methods were analyzed and compared, and the relationship between the two methods and the clinicopathological characteristics of invasive BUC was discussed.The correlation between the protein expression of Nectin-4 in BUC tissues, human epidermal growth factor receptor 2 (Her-2) and programmed death factor ligand 1 (PD-L1) was analyzed. [Results] The positive protein expression rates of Nectin-4 detected by IHC were 78.33%(47/60) and 17.50% (7/40) in the invasive BUC group and inflammatory group, respectively, while the positive mRNA expression rates of Nectin-4 detected by RNAscope were 83.33% (50/60) and 12.50% (5/40), respectively.The Kappa values of Nectin-4 in the invasive BUC group and inflammatory group were 0.732 and 0.610, respectively, with general consistency.The protein expression of Nectin-4 in invasive BUC was correlated with muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The mRNA expression of Nectin-4 in invasive BUC was correlated with max tumor diameter, muscular invasion, histological grade, vascular thrombus, lymph node metastasis and clinical stage (P<0.05). The high expression of Nectin-4 in invasive BUC was positively correlated with the expression of Her-2 (P=0.002), but not with the expression of PD-L1 (P>0.05). [Conclusion] Nectin-4 is highly expressed in invasive BUC, and is usually associated with the pathological parameters of poor prognosis.Detection of Nectin-4 expression will help to guide clinical diagnosis and treatment.

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

OBJECTIVE: To explore the clinical characteristics, genetic basis and clinical treatment of seven neonates with congenital nephrogenic diabetes insipidus (NDI). METHODS: Clinical data of the patients were collected. High-throughput sequencing was carried out to detect potential variants. Sanger sequencing was used to verify the results. RESULTS: The patients were all males, with the age of onset being 10 to 21 days. All patients were admitted to the hospital for intermittent fever as the first symptom during the neonatal period. Additional symptoms had included polydipsia and polyuria. After the treatment, 5 patients had recovered, the remainders still had NDI symptoms and developmental retardation. Five children were found to harbor pathogenic variants of the AVPR2/AQP2 gene, which included one in-frame mutation of c.645_646insGCACCTACCCTGGGTATCGCC, two missense mutations of c.541C>T and c.419C>A, and two hemizygous deletions of the AVPR2/AQP2 gene. Among these, two were unreported previously. Cases 6 and 7 were a pair of twins. Both had carried homozygous missense variants of c.538G>A of the AVPR2/AQP2 gene, which was known to be pathogenic. CONCLUSION AVPR2/AQP2 is the main pathogenic gene for congenital NDI, for which two novel pathogenic variants have been discovered in this study. Above results have provided a basis for clinical diagnosis and genetic counseling for the affected pedigrees.
Aquaporin 2/genetics* ; Child ; Diabetes Insipidus, Nephrogenic/genetics* ; Diabetes Mellitus ; Humans ; Infant, Newborn ; Male ; Molecular Biology ; Mutation ; Pedigree ; Receptors, Vasopressin/genetics*

Objective:To establish a simple and efficient clinical prediction model of moderate and severe obstructive sleep apnea hypopnea (OSAHS) in snoring patients based on the clinical data and morphological measurement data in order to increase the early diagnosis and then early intervention of OSAHS. The prediction model is evaluated by external validation.Methods:A total of 299 subjects from January 2015 to December 2018 were selected to perform polysomngraphy (PSG) in Yangpu Hospital, Tongji University School of Medicine. According to the PSG results, they were divided into moderate and severe OSAHS groups (143 cases) and control groups (156 cases). Clinical complications data and morphological measurement data were collected. The regression equation and ROC curve were established according to the Logistic regression method. Then, another 110 subjects from January 2019 to October 2019 were chosen as verified data group, and used to verify the accuracy of the prediction model. The data of 110 subjects were put into the equation according to risk factors and assignment. The ROC curve was drawn and the area under the curve was calculated. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were calculated.Results:The predicted equation was: y = -10.707 86+0.589 60 × sex+ 0.141 61 × BMI+ 1.281 62 × tonsil size degree+ 1.807 43 × modified Mallampati degree′tongue position. The AUC of the ROC curve of prediction model in training set was 0.851(95% CI 0.807-0.895), the sensitivity was 83.9%, the specificity was 79.5%, and the cut-off value was 0.634.The AUC of the ROC curve in validation set was 0.827(95% CI 0.751-0.904) with a sensitivity of 73.3% and a specificity of 86.0%, and an accuracy of 79.1%. Its positive predictive value was 5.238, and negative predictive value was 0.310. Conclusions:The predictive model constructed by the combination of clinically accessible data (sex) and morphological measurement (BMI, tonsil size degree, modifiedMallampatidegree) has a relatively high predictive efficiency for screening snoring patients with moderate and severe OSAHS. The predictive model is proved with good forecast accuracy by the external verification method.

Objective:To investigate the mastery and application of medical ethics basic knowledge in geriatric ward medical staffs,and the way which they receive relevant education. Methods:From November 2016 to January 2017,240 questionnaires about medical ethics were distributed among medical staffs in clinical department in the Chinese PLA General Hospital,among them,30 were medical groups and 210 were nursing groups;and a total of 233 valid questionnaires were collected. The nurses were divided into geriatric ward nursing group and non - geriat-ric ward nursing group,according to whether they work in the geriatric wards or not. Results:Only 2. 14％ and 7. 72％ participants fully and correctly answered the core concepts and basic principles of medical ethics,respec-tively. The rate of informed consent in medical staffs in geriatric group was significantly higher than that of non -geriatric group (92. 66％ vs 82. 11％ ,P = 0. 02);the patient' s privacy protection in geriatric nursing group was significantly higher than that of non - geriatric nursing group (92. 66％ vs 31. 57％ ,P < 0. 001). 28. 75％ of the respondents received medical ethics continuing education curriculum,and the proportion of correctly receiving ex-pectable death in these medical staffs (71. 40％ ) was significantly higher than that of other education pathway groups (36. 17％ ). Conclusion:Medical staffs lack more knowledge on medical ethics. Clinical work in geriatric medicine has higher demand for medical ethics knowledge,and continuing medical education can help to improve the cognitive level of medical ethics in medical staffs.

Objective To demonstrate the effect of comprehensive treatment under nasal endoscopy for epistaxis. Methods The bleeding sites of 92 patients were defined by nasal endoscopic examination. Epistaxis was cured by single pole or bipolar coagulation, combined with micro packing and systemic treatment. The bleeding sites and effect were studied retrospectively. Results The hemorrhagic foci were found in the following sites: 60.87%(56/92) in Little area, 13.04%(12/92) in the middle and back of nasal septum, 10.87% (10/92) in olfactory sulcus, 8.70% (8/92) in middle turbinate , 3.26% (3/92) at the top of inferior meatus, 2.17% (2/92) at the top of nasal cavity, 1.09% (1/92) at unknown part at the back of nasal cavity. Epistaxis was successfully controlled by once nasal endoscopic examation and hemostasis in 86 of 92 patients. While in 5 of 92 patients, epistaxis was cured by twice nasal endoscopic examation and hemostasis. Endoscopicligation of the sphenopalatineartery was performed in 1 patient with unknown posteriorepistaxis. In 92 patients,15 cases were given micro packing combined with systemic treatment. All the patients were cured and were followed up for 3 months without recurrence and the cure rate was 100.00%. Conclusions The major bleeding site is Little area. Single pole or bipolar coagulation, combined with micro packing and systemic treatment under nasal endoscope is effective for epistaxis and worth of clinic application extensively.

Objective To evaluate the effect of transnasal optic nerve decompression for traumatic optic neuropathy in different surgery time. Methods The databases of the Cochrane library, Embase, PubMed, Wanfang Database, China Journal Full-text Database (CNKI), Weipu Database(VIP) were searched for retrospective studies and clinical controlled trials. The search words included traumatic optic neuropathy, TON, eye traumas, transnasal endoscopicoptic decompression, TEOND, decompression of optic canal and endoscopy. According to the inclusion and exclusion criteria, the data were extracted. The RevMan 5.3 was used to analyze the data. Results All of 1 087 studies were detected. Sixteen eligible studies were enrolled, including 803 eyes. Meta analysis showed that the recovery degree of visual acuity, curative effect in operation group within 7 d of trauma was obviously superior to the operation group 7 d after trauma (OR=2.78;95%CI:2.02-3.82;P<0.01). Conclusions Transnasal endoscopic optic nerve decompression in treatment of traumatic optic neuropathy should be operated as soon as possible, and it is better to operate within 7 d.