ObjectiveTo analyze the characteristics and influencing factors of elderly hospitalized patients with carbapenem-resistant gram-negative bacillus (CRO) infection in the intensive care unit (ICU) of a gradeⅡ level A general hospital in Yangpu District of Shanghai, and to provide scientific basis for the prevention and control of hospital-acquired CRO infection in such hospitals. MethodsThe clinical data of elderly ICU patients (age ≥60 years) from January 2019 to December 2023 were retrospectively collected. A total of 122 cases with hospital-acquired CRO infection were used as the case group, and a total of 68 cases with carbapenem-sensitive gram-negative (CSO) infection were used as the control group. The clinical characteristics of the two groups were analyzed, and univariate analysis and logistic regression analysis were performed for screening for possible influencing factors on hospital-acquired CRO infection. ResultsThe main pathogens of CRO infection were carbapenem-resistant Acinetobacter baumannii (CRAB) (53 cases, 43.44%) and carbapenem-resistant Klebsiella pneumoniae (CRKP) (46 cases, 37.70%), and 17 patients (13.93%) had more than two types of CRO infection. Among the CRO infection, the main sites were lower respiratory tract infection (58 cases, 47.54%), ventilator-associated pneumonia (21 cases, 17.21%), and catheter-associated urinary tract infections (16 cases, 13.11%). The incidence rate of poor prognosis was higher in the CRO infection group (54.10%) than that in the CSO infection group (36.76%) (P=0.021). The results of univariate analysis showed that male, history of hospitalization within three months, chronic respiratory disease, hypoproteinemia, anemia, and history of invasive procedures prior to infection, including indwelling central venous catheter, invasive mechanical ventilation, urinary catheter, gastric tube placement and parenteral nutrition, in addition, heparin anticoagulation, the use of broad-spectrum penicillin, third-generation cephalosporins, fluoroquinolones, carbapenems, carbapenems combined with fluoroquinolones, carbapenems combined with glycopeptides, use of ≥3 antibiotics and long time of antibiotic use prior to infection were all associated with the CRO infection (P<0.05). The results of logistic regression analysis showed that use of carbapenems (OR=7.739, 95%CI: 2.226‒26.911), ≥3 types of antibiotics (OR=6.307, 95%CI: 1.674‒23.754), invasive mechanical ventilation (OR=4.082, 95%CI: 1.795‒9.281), urinary catheter (OR=3.554, 95%CI: 1.074‒11.758), and comorbid hypoproteinemia (OR=4.741, 95%CI: 2.039‒11.022) and diabetes (OR=3.245, 95%CI: 1.344‒7.839) were positively correlated with the risk of CRO infection. ConclusionConcurrent use of carbapenems with multiple other antibiotics, as well as the use of invasive mechanical ventilation, urinary catheter, and comorbid hypoproteinemia and diabetes, may be associated with an increased influencing of CRO infection. More attention should be paid to the prevention and control of infection in elderly patients with the above-mentioned risk factors, and active screening of drug-resistant bacteria should be strengthened. Besides, the rational use of broad-spectrum antibiotics such as carbapenems, avoiding unnecessary invasive operations, and paying attention to patient nutrition and blood glucose control all can reduce the incidence of CRO infection and help to improve clinical outcomes.

OBJECTIVE: To summarize the gene therapy strategies for neurofibromatosis type 1 (NF1) and related research progress. METHODS: The recent literature on gene therapy for NF1 at home and abroad was reviewed. The structure and function of the NF1 gene and its mutations were analyzed, and the current status as well as future prospects of the transgenic therapy and gene editing strategies were summarized. RESULTS: NF1 is an autosomal dominantly inherited tumor predisposition syndrome caused by mutations in the NF1 tumor suppressor gene, which impair the function of the neurofibromin and lead to the disease. It has complex clinical manifestations and is not yet curable. Gene therapy strategies for NF1 are still in the research and development stage. Existing studies on the transgenic therapy for NF1 have mainly focused on the construction and expression of the GTPase-activating protein-related domain in cells that lack of functional neurofibromin, confirming the feasibility of the transgenic therapy for NF1. Future research may focus on split adeno-associated virus (AAV) gene delivery, oversized AAV gene delivery, and the development of new vectors for targeted delivery of full-length NF1 cDNA. In addition, the gene editing tools of the new generation have great potential to treat monogenic genetic diseases such as NF1, but need to be further validated in terms of efficiency and safety. CONCLUSION Gene therapy, including both the transgenic therapy and gene editing, is expected to become an important new therapeutic approach for NF1 patients.
Humans ; Neurofibromatosis 1/pathology* ; Neurofibromin 1/metabolism* ; GTPase-Activating Proteins ; Mutation ; Genetic Predisposition to Disease ; Genetic Therapy

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.

BACKGROUND:Atlantoaxial dislocation is often facilitated by interlaminar bone grafting.However,there are relatively few reports on the treatment of complex atlantoaxial dislocation with posterior atlantoaxial lateral mass interarticular release and fusion. OBJECTIVE:To explore the safety and effectiveness of atlantoaxial dislocation treated by simple posterior atlantoaxial lateral block interarticular release and fusion. METHODS:We retrospectively analyzed the clinical data of 30 patients with atlantoaxial dislocation who were treated from January 2017 to July 2021,all of whom suffered from reducible atlantoaxial dislocation.Posterior atlantoaxial lateral mass interarticular release and fusion were performed in all patients.During the surgery,patented instruments were used to release the atlantoaxial lateral mass joint,and posterior screw reduction and fixation were used with bone grafting in the lateral mass joint space.The postoperative follow-up period was 6 to 24 months,mean(13.0±5.4)months.During the follow-up period,cervical MRI was reviewed to observe the decompression of the upper cervical spine.X-ray films and CT scans were reviewed to observe the reduction of the upper cervical spine,as well as the internal fixation for looseness and breakage.CT scans were reviewed to assess interlateral block implant fusion.The Japanese Orthopaedic Association score was used to evaluate the improvement of spinal cord function.The neck disability index and the quality of life scale were used to assess the improvement of daily life function.The atlanto-anterior interspace and atlanto-planar spinal effective space were used to evaluate atlantoaxial repositioning and decompression. RESULTS AND CONCLUSION:(1)The surgery of 30 patients went smoothly,and no serious complications such as spinal nerve and vertebral artery injuries occurred during the operation.Postoperative review of cervical MRI showed that the spinal cord compression was lifted.X-ray film and CT showed that the atlanto-anterior gap was significantly reduced;the effective space of atlantoaxial spinal cord was significantly increased,and neurological dysfunctional symptoms were significantly reduced.(2)During the follow-up period,X-ray film and CT showed that the internal fixation was solid;no broken nails or rods occurred,and there was no recurrence of atlantoaxial dislocation.(3)The Japanese Orthopaedic Association scores,neck disability index,and quality of life scores were significantly improved at the last follow-up compared with the preoperative period(P<0.05).The average improvement rate of Japanese Orthopaedic Association scores at the last follow-up was 73.1%.The average neck disability index was 8.80%.All of the patients had a continuous bone-scalp connection between atlantoaxial lateral block joints to achieve osseous fusion.(4)These findings indicate that the use of simple posterior atlantoaxial lateral block interarticular release and fusion for the treatment of atlantoaxial dislocation can significantly increase the fusion rate and shorten the fusion time.

Objective:The treatment of head and neck in plexiform neurofibroma (PNF) is a major clinical problem, lacking consensus on surgical treatment, classification, operation timing, and treatment method. The purpose of this study was to provide a basis for further consensus formation by analyzing the clinical manifestations, surgical conditions, tumor recurrence, post-operation satisfaction, and changes in quality of life of patients undergoing PNF surgery in head and neck.Methods:Through medical record review and telephone follow-up, a retrospective analysis was conducted on neurofibromatosis type 1 (NF1) patients admitted for surgical treatment for PNF patient in head and neck from May 2012 to July 2022 in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Complete collection and statistical analysis of patients’clinical data, using telephone follow-up to investigate the immediate postoperative satisfaction and long-term surgical satisfaction of patients and/or their families, as well as standardized quality of life questionnaires HRQol(health related quality of life) and PlexiQol(plexiform neurofibroma quality of life). Based on the data about changes in quality of life before and after surgery and long-term surgical satisfaction, patients were divided into surgical benefit and non-benefit groups. Binary and multivariate logistic regression analysis were used to analyze the clinical characteristics of patients with long-term surgical benefit.Results:Totally 512 patients with head and neck NF1 were admitted for surgery with complete medical records. 121 patients were identified as NF1 related PNF diagnosed by medical history and radiological examination, and effective follow-up was obtained. There were 70 males and 51 females, aged (25.60±12.85) years old, ranging from 7 to 63 years old, with 41 patients who were ≤ 18 years old and 80 patients over 18 years old. 62.81%(76/121) of patients exhibiting clinical dysfunctions, and the tumor mass were mainly characterized by invasive growth. 41.32%(50/121) of patients underwent multiple surgical treatments, with a total of 215 surgeries performed on 121 patients. The surgical objective included appearance improvement and functional repair. The incidence of postoperative complications was 6.05%(13/215). The follow-up period after last operation was (51.41±27.66) months, and 42.15%(51/121) of patients reported postoperative tumor recurrence. 76.03%(92/121) of patients were satisfied with immediate postoperative result, while the rate decreased to 46.28%(56/121) during long-term follow-up. Family members of patients who were ≤ 18 years old had a higher proportion of dissatisfaction with the scars caused by surgery and a stronger willingness to undergo another surgery. The tumor recurrence was closely related to surgical benefits ( OR=2.32, P<0.05). Further analysis found that the gender and age of patients were the main risk factors for the recurrence. The recurrence risk in patients ≤ 18 years old was significantly higher than in that over 18 years old( OR=3.49, P=0.004), and the highest in the 7-12 year-old group, reaching 68.42%(13/19). The recurrence risk in male patients was significantly lower than that in females ( OR=0.40, P=0.026). Conclusion:The clinical manifestations of PNF patients in head and neck region are complex. Clinical diagnosis and treatment in PNF should focus on the applications in comprehensive method such as full preoperative evaluation, active multi-disciplinary treatment cooperation and combined therapies in order to improve the safety and effectiveness of treatment and reduce tumor recurrence.

Objective To explore the effect of teaching mode based on ICARE on the professional spirit attitude of intravenous therapy specialist nurses.Methods 100 specialized intravenous therapy nurses who were trained in the Fourth Affiliated Hospital of Harbin Medical University from October 2021 to October 2022 were randomly divided into control group and experimental group.The control group students completed the training with traditional methods,while the experimental group students completed the training with the guidance of ICARE.Before and after the training,the professional spirit and attitude of the two groups of students was evaluated.Results After the implementation of the study,it was verified through independent sample r-test that the public services,autonomy and nurse job satisfaction of professional spirit and attitude scores group students was significantly higher than that of the control group(P＜0.05),and the difference was statistically significant.The Chi-squared test verified that the total incidence of complications of intravenous catheterization in the experimental group was significantly lower than that in the control group,with a statistically significant difference(P＜0.05).Conclusion The teaching mode based on ICARE can significantly improve the professional spirit and attitude of the intravenous treatment specialist nurses and the quality of intravenous infusion treatment.

Objective:To compare the characteristics of background mucosa, lesion features, and the efficiency of endoscopic submucosal dissection(ESD)between elderly and non-elderly patients with early gastric cancer(EGC).Methods:This study retrospectively collected data on patients with EGC who underwent ESD treatment at Beijing Hospital from April 2020 to December 2022.The clinical characteristics, background mucosa, lesion features, ESD outcomes, and pathological results of the patients were analyzed to compare the differences between elderly and non-elderly patients.Results:A total of 100 patients with EGC were selected, comprising 57 patients in the elderly group and 43 patients in the non-elderly group, with a total of 111 lesions identified(64 lesions in the elderly group and 47 lesions in the non-elderly group).The proportion of patients with a history of chronic atrophic gastritis was significantly higher in the elderly group(89.5%、51/57)compared to the non-elderly group(74.4%、32/43), with a statistically significant difference( P=0.047).Additionally, the difference in the extent of atrophy between elderly patients with EGC and their non-elderly counterparts was statistically significant( P=0.022).Among these patients, the proportion of those classified as Kimura-Takemoto C0 to C1 in the elderly group(15.6%、10/64)was lower than that in the non-elderly group(40.4%、19/47).In contrast, the proportion of patients classified as C2 to C3 in the elderly group(65.6%、42/64)was higher than that in the non-elderly group(51.1%、24/47), and the proportion of those classified as O1 to O3 in elderly patients(12.5%、8/64)was also higher than in the non-elderly group(4.3%、2/47).Furthermore, the difference in the extent of intestinal metaplasia between elderly and non-elderly patients with early gastric cancer was statistically significant( P=0.007).The overall proportion of total intestinal metaplasia in elderly patients(85.9%、55/64)was significantly higher than that in non-elderly patients(61.7%、29/47).Notably, the proportion of patients exhibiting extensive intestinal metaplasia(intestinal metaplasia present in both the gastric antrum and gastric body)was greater in the elderly group(43.8%、28/64)compared to the non-elderly group(23.4%、11/47).The Kyoto gastric cancer risk endoscopic score for elderly patients with EGC was(2.43±1.28)points, significantly higher than that of the non-elderly group(1.72±1.41)points, with a statistically significant difference observed( t=2.778, P=0.006).No statistically significant differences were observed in the proportions of total resection rates, R0 resections, curative resections, or postoperative complications following ESD when comparing elderly patients with EGC to their non-elderly counterparts. Conclusions:The proportion of extensive atrophy and intestinal metaplasia was higher in the background mucosa of elderly patients with EGC, and correspondingly, the Kyoto endoscopic gastric cancer risk score was elevated.Therefore, endoscopic examinations for elderly patients with chronic atrophic gastritis should be conducted with greater care and comprehensiveness.

The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

Objective To explore the effect of pregabalin on sleep of patients after video-assisted thoracic surgery(VATS).Methods 120 cases of patients undergoing VATS under general anesthesia were randomly divided into 75 mg pregabalin group(group A),150 mg pregabalin group(group B),and placebo group(group C),with 40 patients in each group.On the night of the operation,the morning and evening of the first day and the second day after the operation,the patients in the three groups were given one tablet of pregabalin(75 mg),one tablet of placebo with the same shape and smell,two tablets of pregabalin(150 mg)and two tablets of placebo with the same shape and smell respectively.Athens insomnia scale(AIS)was used to evaluate the incidence of postoperative sleep disturbance(PSD)on the night of operation,and the patients'sleep quality every night from one night before operation to the 2nd day after operation was assessed using the St.Mary's Hospital sleep questionaire(SMH).Pittsburgh sleep quality index(PSQI)was used to evaluate the patients'sleep quality one day before the operation,7 days after operation,and 1 month after the operation.The digital rating scale(NRS)was used to evaluate the patients'pain at the incision and the surgical side.The remedial analgesia,incidence of adverse events in the 72 h postoperative period,and patient satisfaction score were recorded.Results The incidence of PSD in group A,group B and group C was 45.0％,42.5％and 72.5％,respectively,the incidence of group A and group B was significantly lower than in group C(group A,B and C compared in pairs,P＜0.016 7).The SMH scores in group A and group B were significantly higher than in group C on the day of operation,the first day and the second day after operation(group A,B and C compared in pairs,P＜0.016 7).The incidence of NRS scores in groups A and B at the incision and postoperative remedial analgesia was significantly lower than in group C on postoperative day 1 and postoperative day 2(group A,B and C compared in pairs,P＜0.016 7).There was no statistically significant difference in the pain scores at the incision and shoulder among the three groups at the remaining time points.The postoperative patient satisfaction scores were significantly higher in group A and group B than in group C(P＜0.01).The incidence of dizziness in group B was significantly higher than in the other two groups(P＜0.016 7).Conclusion Oral administration of pregabalin(75 mg/150 mg)for 3 days after VATS can reduce the incidence of PSD and improve the quality of sleep that night,but oral administration of 150 mg pregabalin may increase the incidence of dizziness.

Background::Ebstein’s anomaly (EA) is a rare and complex congenital heart anomaly, and the effect of surgical treatment is not ideal. This study aims to introduce our experience in management strategies, surgical techniques, and operative indications for patients with Ebstein’s anomaly.Methods::A retrospective study of 258 operations was performed in 253 patients by the same cardiac surgeon in The First Hospital of Tsinghua University between March 2004 and January 2020. 32 patients had previously received cardiac surgery in other hospitals. The clinical data including diagnosis, operative indications, techniques, pathological changes, and survival rates were collected and analyzed.Results::Anatomical correction was performed in 203 (78.7%) operations, 1? ventricle repair in 38 (14.7%) operations, tricuspid valve repair only in four operations (1.6%), tricuspid valve replacement in ten (3.9%), total cavopulmonary connection (TCPC) in two (0.8%), and Glenn operation in one operation (0.4%). Reoperation was performed in five patients (2.0%) during hospitalization. Among them, tricuspid valve replacement was performed in one patient, 1? ventricle repair in two patients, and tricuspid valve annulus reinforcement in two patients. Five patients died with an early mortality rate of 2.0%. Complete atrioventricular conduction block was complicated in one patient (0.4%). A total of 244 patients was followed up (four in the 253 patients lost) with a duration of 3.0-168.0 (87.6 ± 38.4) months. Cardiac function of 244 patients improved significantly with mean New York Heart Association (NYHA) functional class recovery from 3.5 to 1.1. The mean grade of tricuspid valve regurgitation improved from 3.6 to 1.5. Three late deaths (1.2%) occurred. The survival rates at five and ten years after surgery were 98.6% and 98.2%, respectively. Reoperation was performed in five patients (2.0%) during the follow-up period.Conclusion::Based on our management strategies and operative principles and techniques, anatomical correction of EA is capable of achieving excellent long-term results, and low rates of TCPC, 1? ventricle repair and valvular replacement.