Objective:To investigate the factors contributing to in-hospital mortality among elderly patients aged 80 and above with gastrointestinal bleeding(GIB).Additionally, it seeks to assess the predictive ability of the electronic frailty index(eFI)in determining the risk of in-hospital mortality in GIB patients.Methods:A retrospective analysis was performed among 624 patients aged 80 and above with GIB who were admitted to Beijing Hospital between July 2013 and September 2019.The patients were categorized into two groups based on their discharge outcomes: those who survived and those who did not.The eFI was developed using a cumulative deficit model utilizing data from the hospital's electronic medical records.The study examined the clinical features and risk factors associated with in-hospital mortality among these elderly patients.The effectiveness of eFI in predicting in-hospital mortality in elderly patients with gastrointestinal bleeding was evaluated by calculating the area under the curve(AUC)of the receiver operating characteristic(ROC)curve.Results:Among a total of 624 patients aged between 80 and 102 years, the average age was(83.0±6.4)years, with 339 being male.A majority of the patients, 581 cases(93.1%), had an eFI ≥ 0.15.A comparison between the survival group(380 cases)and the death group(244 cases)revealed that the latter had higher eFI values(0.39±0.09 vs.0.29±0.11, t=-11.452, P<0.001), along with higher rates of heart failure, chronic kidney disease, and malignant tumors, as well as lower body mass index, hemoglobin, albumin, and total cholesterol levels, and higher alanine aminotransferase and D-dimer levels(all P<0.05).Logistic regression analysis indicated that eFI( OR=2.322, 95% CI: 1.840-2.929, P<0.001), malignant tumor( OR=1.833, 95% CI: 1.141-2.860, P<0.001), and albumin<35 g/L( OR=1.826, 95% CI: 1.200-2.777, P<0.001)were independent risk factors for in-hospital death in elderly patients aged 80 and over with gastrointestinal bleeding.With every 0.1 increase in eFI, the risk of in-hospital death rose by 1.322 times.The AUC of eFI for predicting in-hospital mortality was 0.751(95% CI: 0.713-0.789, P<0.001).An eFI of ≥0.33 demonstrated a sensitivity of 77.9% and a specificity of 60.3% in predicting in-hospital mortality in elderly patients aged 80 and over with GIB. Conclusions:The eFI serves as an important independent risk factor for in-hospital mortality among patients aged 80 and above who experience GIB.It can effectively assess the prognosis of elderly individuals facing GIB.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

Objective　To investigate the biological characteristics of the serine protease inhibitor 15 (RmS-15) protein of Rhipicephalus microplus, and to perform molecular cloning and prokaryotic expression. Methods RmS-15 gene was amplified and sequenced to construct a phylogenetic tree to understand its evolutionary relationships. Bioinformatic tools were used to analyze the physicochemical properties, signal peptide, secondary and tertiary structure of the RmS-15 protein. In addition, DNA star and ABCpred were used to predict potential B-lymphocyte antigenic epitopes of RmS-15 protein, and potential T-lymphocyte antigenic epitopes were predicted by SYF-PEITHI and IEDB. Finally, the RmS-15 recombinant protein of Rhipicephalus microplus was obtained using the E.coli prokaryotic expression system and purified. Results The RmS-15 gene with 1 212 bp was successfully amplified, encoding a protein comprising 403 amino acids. Phylogenetic tree results indicated high conservation of the RmS-15 protein among different tick amino acid sequences, with the closest phylogenetic relationships to the Rhipicephalus haemaphysaloides and the Rhipicephalus sanguineus. The results of physicochemical property analysis showed a 20-amino acid signal peptide at the N-terminus of the RmS-15 protein, with a relative molecular weight and theoretical isoelectric point of 44 000 and 6.68, respectively. The protein showed an average hydrophilicity of 0.001, classifying it as a stably hydrophilic protein. The results of antigenicity analysis showed that the dominant fragments of B-cell antigenic epitopes of RmS-15 protein were 102-112 aa,147-152 aa and 207-215 aa, and the dominant fragments of T-cell antigenic epitopes were 3-11 aa, 6-14 aa, 27-33 aa, 34-37 aa. Protein expression results showed that RmS-15 protein exhibited high expression levels in the supernatant after induction with 0.8 mmol/L IPTG at 16 ℃ for 24 hours and reached a successful purification with a single band of the protein molecular weight of 44 000. Conclusions The method of prokaryotic expression and purification of RmS-15 protein from Rhipicephalus microplus was successfully established. Bioinformatics analysis demonstrated its strong antigenicity, suggesting its potential to develop as a candidate vaccine for ticks.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15％ of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5％?49.7％ of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3％?17.9％, which was significantly higher than that (6.9％?7.4％) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

This paper expounds that the construction of a clinical teacher's teaching ability model is an urgent problem to be solved in medical colleges and universities, and analyzes that the current clinical teaching concepts and methods are constantly improving, and the clinical teaching environment is more informatized and intelligent. This paper summarizes the clinical teachers' teaching ability models at home and abroad, such as the ability and quality iceberg model, teacher growth model, inquiry-based teaching model, Molenaar three-dimensional teaching ability model, etc., and discusses the practice research progress of current clinical teacher teaching ability models such as student-centered guided teaching, bedside teaching, micro-teaching and BOPPPS (bridge-in, objective, pre-assessment, participatory-learning, post-assessment, and summary) method, medical simulation teaching, etc., hoping to provide guidance for further constructing models of teacher's teaching ability suitable for Chinese medical colleges and universities.

Objective: To investigate the safety and feasibility of laparoscopic operation in thetreatment of gastric gastrointestinal stromal tumor (GIST) at unfavorable positions. Methods: A retrospective cohort study was conducted to analyze the clinical data of patients with gastric GIST at unfavorable positions confirmed by pathology after surgery (laparoscopy or laparotomy) at the Southwest Hospital of the Army Medical University and the Minda Hospital of Hubei Minzu University from June 2008 to June 2018. The unfavorable positions of stomach are defined as the esophagogastric junction, the proximal cardia of gastric lesser curvature, the pylorus of stomach, the posterior wall of stomach and the antrum of stomach.Exclusion criteria:(1) preoperative chemotherapy or imatinib therapy; (2) diameter of tumor > 10 cm; (3) tumor metastasis or concurrence of other malignant tumors. A total of 244 patients (238 in Southwest Hospital and 6 in Minda Hospital) were enrolled, including 122 males and 122 females with age of 41-70years. Operative methods should be adopted according to patients' wishes. There were 146 cases in the laparoscopic surgery group and98 cases in the open surgery group. The intraoperative blood loss, operative time, postoperative first flatus time, postoperative firstfeeding time,average hospital stay, morbidity of postoperative complication,1-,3-,and 5-year recurrence free survival(RFS) and overall survival (OS)rate were compared between the two groups. Results: There were no significant differences in sex, age, tumor size, tumor risk grade or growth pattern between the laparoscopic and the open surgery groups (all P>0.05),and these two groups were comparable. Compared with open group, laparoscopic group had less intraoperative blood loss [(31.4±2.3) ml vs. (143.9±3.7) ml, t=292.800, P<0.001], shorter postoperative first flatus time [(2.1±0.7) days vs.(3.8±0.8) days, t=17.550,P<0.001], shorter postoperative first feeding time [(2.1±0.5) days vs.(2.3±1.7) days, t=1.339,P=0.020], shorter hospital stay [(8.6±2.6) days vs. (13.6±3.2) days, t=13.410, P<0.001], and lower morbidity of postoperative complication [16(11.0%) vs. 21(21.4%),χ²=4.996,P=0.025], whose differences were statistically significant. While the operation time was similar in two groups [(124.7±15.8) minutes vs. (120.9±14.5) minutes, t=1.903,P=0.058]. The median follow-up of all the patients was 43 (1 to 119) months.In laparoscopic group and open group, the 1-, 3- and 5-year RFS were 94.5% vs. 93.9%, 91.1% vs. 90.8%,and 82.2% vs. 81.6%, respectively, and 1-, 3- and 5-year OS were 98.6% vs. 95.9%, 95.9% vs. 94.9%,and 91.1% vs. 88.8%, respectively, whose differences were not statistically significant (all P>0.05). Conclusion In the experienced gastrointestinal surgery center, laparoscopic resection of gastric GIST at unfavorable position is safe and feasible, achieving the same efficacy of open surgery.

Objective To investigate the safety and feasibility of laparoscopic operation in thetreatment of gastric gastrointestinal stromal tumor (GIST) at unfavorable positions. Methods A retrospective cohort study was conducted to analyze the clinical data of patients with gastric GIST at unfavorable positions confirmed by pathology after surgery (laparoscopy or laparotomy) at the Southwest Hospital of the Army Medical University and the Minda Hospital of Hubei Minzu University from June 2008 to June 2018. The unfavorable positions of stomach are defined as the esophagogastric junction, the proximal cardia of gastric lesser curvature, the pylorus of stomach, the posterior wall of stomach and the antrum of stomach. Exclusion criteria: (1) preoperative chemotherapy or imatinib therapy; (2) diameter of tumor>10 cm; (3) tumor metastasis or concurrence of other malignant tumors. A total of 244 patients (238 in Southwest Hospital and 6 in Minda Hospital) were enrolled, including 122 males and 122 females with age of 41?70years. Operative methods should be adopted according to patients' wishes. There were 146 cases in the laparoscopic surgery group and98 cases in the open surgery group. The intraoperative blood loss, operative time, postoperative first flatus time, postoperative firstfeeding time, average hospital stay, morbidity of postoperative complication,1?,3?,and 5?year recurrence free survival(RFS) and overall survival (OS)rate were compared between the two groups. Results There were no significant differences in sex, age, tumor size, tumor risk grade or growth pattern between the laparoscopic and the open surgery groups (all P>0.05), and these two groups were comparable. Compared with open group, laparoscopic group had less intraoperative blood loss [(31.4 ± 2.3) ml vs. (143.9 ± 3.7) ml, t=292.800, P<0.001], shorter postoperative first flatus time [(2.1 ± 0.7) days vs. (3.8 ± 0.8) days, t=17.550, P<0.001], shorter postoperative first feeding time [(2.1±0.5) days vs.(2.3±1.7) days, t=1.339,P=0.020], shorter hospital stay [(8.6±2.6) days vs. (13.6±3.2) days, t=13.410, P<0.001], and lower morbidity of postoperative complication [16(11.0%) vs. 21(21.4%), χ2=4.996, P=0.025], whose differences were statistically significant. While the operation time was similar in two groups [(124.7±15.8) minutes vs. (120.9±14.5) minutes, t=1.903,P=0.058]. The median follow?up of all the patients was 43 (1 to 119) months.In laparoscopic group and open group, the 1?, 3? and 5?year RFS were 94.5% vs. 93.9%, 91.1% vs. 90.8%,and 82.2% vs. 81.6%, respectively, and 1?, 3?and 5?year OS were 98.6% vs. 95.9%, 95.9% vs. 94.9%,and 91.1% vs. 88.8%, respectively, whose differences were not statistically significant (all P>0.05). Conclusion In the experienced gastrointestinal surgery center, laparoscopic resection of gastric GIST at unfavorable position is safe and feasible, achieving the same efficacy of open surgery.

Objective To investigate the safety and feasibility of laparoscopic operation in thetreatment of gastric gastrointestinal stromal tumor (GIST) at unfavorable positions. Methods A retrospective cohort study was conducted to analyze the clinical data of patients with gastric GIST at unfavorable positions confirmed by pathology after surgery (laparoscopy or laparotomy) at the Southwest Hospital of the Army Medical University and the Minda Hospital of Hubei Minzu University from June 2008 to June 2018. The unfavorable positions of stomach are defined as the esophagogastric junction, the proximal cardia of gastric lesser curvature, the pylorus of stomach, the posterior wall of stomach and the antrum of stomach. Exclusion criteria: (1) preoperative chemotherapy or imatinib therapy; (2) diameter of tumor>10 cm; (3) tumor metastasis or concurrence of other malignant tumors. A total of 244 patients (238 in Southwest Hospital and 6 in Minda Hospital) were enrolled, including 122 males and 122 females with age of 41?70years. Operative methods should be adopted according to patients' wishes. There were 146 cases in the laparoscopic surgery group and98 cases in the open surgery group. The intraoperative blood loss, operative time, postoperative first flatus time, postoperative firstfeeding time, average hospital stay, morbidity of postoperative complication,1?,3?,and 5?year recurrence free survival(RFS) and overall survival (OS)rate were compared between the two groups. Results There were no significant differences in sex, age, tumor size, tumor risk grade or growth pattern between the laparoscopic and the open surgery groups (all P>0.05), and these two groups were comparable. Compared with open group, laparoscopic group had less intraoperative blood loss [(31.4 ± 2.3) ml vs. (143.9 ± 3.7) ml, t=292.800, P<0.001], shorter postoperative first flatus time [(2.1 ± 0.7) days vs. (3.8 ± 0.8) days, t=17.550, P<0.001], shorter postoperative first feeding time [(2.1±0.5) days vs.(2.3±1.7) days, t=1.339,P=0.020], shorter hospital stay [(8.6±2.6) days vs. (13.6±3.2) days, t=13.410, P<0.001], and lower morbidity of postoperative complication [16(11.0%) vs. 21(21.4%), χ2=4.996, P=0.025], whose differences were statistically significant. While the operation time was similar in two groups [(124.7±15.8) minutes vs. (120.9±14.5) minutes, t=1.903,P=0.058]. The median follow?up of all the patients was 43 (1 to 119) months.In laparoscopic group and open group, the 1?, 3? and 5?year RFS were 94.5% vs. 93.9%, 91.1% vs. 90.8%,and 82.2% vs. 81.6%, respectively, and 1?, 3?and 5?year OS were 98.6% vs. 95.9%, 95.9% vs. 94.9%,and 91.1% vs. 88.8%, respectively, whose differences were not statistically significant (all P>0.05). Conclusion In the experienced gastrointestinal surgery center, laparoscopic resection of gastric GIST at unfavorable position is safe and feasible, achieving the same efficacy of open surgery.

Objective To analysis the change of hip joint in healthy infants by ultrasound,and establish the normal reference value of the developmental dysplasia of the hip(DDH). Methods A total of 8 000 healthy infants from 0 to 24 weeks were collected from the Multi-center study of 10 children′s medical centers. Among them,3 855 infants(2 065 females and 1 790 males) with complete data and follow-up were included in this study. All subjects were divided into 6 groups ( ＜4,4～7,8～11,12～15,16～19 and≥20 weeks group). α angle,femoral head length and width,femoral head coverage ratio by acetabulum ( FHC) were measured in the coronal view on the neutral position;distance from pubis to femoral head ( P-H) and distance from ischium to femoral head ( I-H ) were measured in the transverse view on neutral position;distance from femoral head topubis ( H-P) was measured in the posterolateraltransverse view on the flexion position. The results of each group changes with age were analysised. Results ① The α angle of healthy infants from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05),but there was no significant difference between 16～19 and ≥20 weeks group( P ＞0.05). ②The femoral head length and width of all age groups were increased with age,the difference among all the groups was statistically significant( all P ＜0.05). ③ FHC from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05) except between 16～19 and ≥20 weeks group( P ＞0.05). ④ The P-H and I-H in all age groups showed no statistically significant ( all P＞0.05). ⑤The H-P of all age groups were increased with age,the difference between the groups were statistically significant(all P ＜0.05).Conclusions The development of hip joints have the certain regular developmental pattern in healthy infants less than 5 months of birth and are relatively constant after birth more than 5 months. The ultrasound normal reference value of the hip joints can be used for the early diagnosis of the DDH.