Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective:To investigate the application value of three-dimensional (3D) printing technology assisted laparoscopic anatomic liver resection of segment 8 (Lap-S8).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 8 liver cancer patients including 7 cases with hepatocellular carcinoma and 1 case with intrahepatic cholangio-carcinoma who underwent 3D printing technology assisted Lap-S8 in the Hunan Provincial People′s Hospital from January 2019 to December 2020 were collected. There were 7 males and 1 female, aged from 49.0 to 80.0 years, with a median age of 56.5 years. Of the 8 patients, 6 cases underwent laparoscopic anatomic liver resection of the entire segment 8, 1 case underwent laparoscopic anatomic liver resection of ventral subsegmental of the segment 8 and 1 case underwent laparoscopic anatomic liver resection of dorsal subsegmental of the segment 8. 3D printing technology was used to assist preoperative evaluation and intraoperative navigation for all 8 patients. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using outpatient examination, internet or telephone interview to detect survival and tumor recurrence of patients after operation up to March 2021. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations: all the 8 patients underwent 3D printing technology assisted Lap-S8 successfully, without conversion to open surgery. The operation time, hepatic portal occlusion time and volume of intraoperative blood loss of the 8 patients were (216±41)minutes, (56±11)minutes and 75 mL(range, 50 to 300 mL), respectively. There was no intraoperative blood transfusion in 8 patients, and the surgical margin of the 8 patients was negative. (2) Postoperative situations: the duration of postoperative hospital stay of the 8 patients were (9±3)days. There was no complication such as postoperative hemorrhage, biliary fistula, liver abscess or abdominal infection occurred. (3) Follow-up: all the 8 patients were followed up for 3.0?24.0 months, with a median follow-up time of 12.5 months. During the follow-up, 1 of 8 patients with preoperative diagnosis of recurrent hepatocellular carcinoma developed tumor recurrence at 5 months after operation. The patient underwent laparoscopic surgery followed with the transcatheter arterial chemoembolization and target therapy, and survived with tumor. There was no tumor recurrence in the other 7 patients.Conclusion:3D printing technology assisted Lap-S8 is safe and feasible.

Acute abdomen is often a general term for abdominal diseases with acute abdominal pain as the main manifestation. Common clinical acute abdomen includes acute appendicitis, acute cholecystitis, acute cholangitis, acute pancreatitis, gastrointestinal perforation, intestinal obstruction and other diseases, its characteristics are great changes, rapid progress, high misdiagnosis rate, high postoperative complication rate and high mortality rate, accurate diagnosis and early treatment can obtain a good prognosis. With our in-depth understanding of the occurrence and development of acute abdomen diseases and the development of evidence-based medicine, minimally invasive technology plays a pivotal role in the diagnosis and treatment of common acute abdomen. Laparoscopy on diagnosis can clarify disease diagnosis to a large extent. For those who cannot undergo surgery, decompression and drainage under endoscopy provides a diversified plan for treatment decisions. In addition, minimally invasive techniques are also used in etiological treatment and complications. Disease, prevention of recurrence in all aspects, Minimally invasive technology is beneficial to the etiological treatment of biliary pancreatitis, appendicitis and cholangitis, and endoscopic technology is more consistent with the minimally invasive concept in the treatment of complications.

Objective: To investigate the safety and feasibility of longitudinal transpancreatic U-sutures invaginated pancreatojejunostomy (Chen′s pancreaticojejunostomy technique) in laparoscopic pancreaticoduodenectomy (LPD) . Methods: Clinical data of 116 consecutive patients who underwent LPD using Chen′s pancreaticojejunostomy technique in Hunan Provincial People′s Hospital from May 2017 to December 2018 were retrospectively analyzed. Among these patients, 66 were males and 50 were females. The median age was 58 years old (32-84 yeas old). All 116 patients underwent pure laparoscopic whipple procedure with Child reconstruction method, using Chen′s pancreaticojejunostomy technique. The intraoperative and postoperative data of patients were analyzed. Results: All 116 patients underwent LPD successfully. The mean operative time was (260.3±33.5) minutes (200-620 minutes). The mean time of pancreaticojejunostomy was (18.2±7.6) minutes (14-35 minutes) . The mean time of hepaticojejunostomy was (14.6±6.3) minutes (10-25 minutes). The mean time of gastrojejunostomy was (12.0±5.5) minutes (8-20 minutes). The mean estimated blood loss was (106.0±87.6) ml (20-800 ml). Postoperative complications were: 11.2% (13/116) of cases had postoperative pancreatic fistula (POPF) , including 10.3% (12/116) of biochemical fistula and 0.9% (1/116) of grade B POPF, no grade C POPF occurred; 10.3% (12/116) had gastrojejunal anastomotic bleeding; 3.4% (4/116) had hepaticojejunal anastomotic fistula; 3.4% (4/116) had delayed gastric emptying; 4.3% (5/116) had localized abdominal infection; 12.1% (14/116) had pulmonary infection; postoperative mortality were 0(0/116) and 1.7% (2/116) within 30 days and 90 days, respectively. One patient died of massive abdominal bleeding secondary to Gastroduodenal artery pseudoaneurysm rupture, the other patient died of extensive tumor recurrence and metastasis after surgery. Conclusions Chen′s pancreaticojejunostomy technique is safe and feasible for LPD.It is an option especially for surgeons who have not completed the learning curve of LPD.

Objective: To explore the safety and feasibility of laparoscopic liver resection in the treatment of intrahepatic cholangiocarcinoma (ICC). Methods: The retrospective study was adopted. The clinical data of 58 patients with ICC who underwent laparoscopic liver resection in the Department of Hepatobiliary Minimally Invasive Surgery of the First Affiliated Hospital of Hu′nan Normal University were collected From January 2016 to December 2018. Among them, 34 patients were males and 24 were females, aged from 34 to 71 years with a median age of 54 years. Observation indicators: (1) Surgical treatment: surgical methods, operation time, intraoperative blood loss, intraoperative blood transfusion rate, intraoperative hepatic portal blocking time, conversion rate, postoperative complications, postoperative hospital stay. (2) Postoperative pathological conditions. (3) Follow-up.Follow-up visits were conducted using an outpatient clinic and telephone to understand patient survival after surgery. The follow-up period was until June 2019. Measurement data with normal distribution were expressed as (Mean±SD), count data was expressed as frequency and percentage. Results: A total of 58 patients were included in this study, of which 48 patients underwent laparoscopic radical surgical resection of intrahepatic cholangiocarcinoma and 10 patients underwent laparoscopic conversion to laparotomy. (1) Surgical treatment: laparoscopic resection of the left liver (segments Ⅱ, Ⅲ and Ⅳ), laparoscopic resection of the right liver (segments Ⅴ, Ⅵ, Ⅶ and Ⅷ), laparoscopic resection of the right posterior lobe (segments Ⅵ and Ⅶ), laparoscopic extended resection of the right posterior lobe, laparoscopic resection of the middle lobe (Ⅳ, Ⅴ and Ⅷ), laparoscopic resection of the V and Ⅵ, laparoscopic resection of the left liver (segments Ⅱ, Ⅲ and Ⅳ) combined with the caudate lobe (segments I and Ⅸ), laparoscopic extended left hemihepatectomy, laparoscopic resection of the VI, laparoscopic resection of the Ⅶ and Ⅷ, laparoscopic resection of the left lateral lobe (segments Ⅱ and Ⅲ) and laparoscopic resection of the right hepatic mass; operation time: (320.38±107.68) min; intraoperative blood loss: (262.34±76.06); intraoperative blood loss: 0 (0/58); Intraoperative hepatic portal occlusion time: (48±15) min, the conversion rate was 17.2% (10/58); the incidence of postoperative biliary fistula was 6.8% (4/58), and the patient was discharged after conservative treatment and unobstructed drainage (T-tube vacuum suction); the postoperative gastrointestinal recovery time was (1.84±0.57) d; no other serious complications occurred.Postoperative hospital stay: (9.34±3.39) d; there were no deaths and unplanned surgeries during the perioperative period. (2) Pathological conditions: 32 cases received lymph node dissection during the operation, and 26 cases showed cholangiocarcinoma without lymph node dissection; pathological examination showed that the pathological reports of all tumor margins were negative, and 4 cases showed lymph node dissection and positive lymph node metastasis. (3) Follow-up results: of the 58 patients with ICC, 49 were followed up for 6 to 36 months. The tumor survival time was (4 to 36) months. 28 patients survived without tumor. 17 patients had intrahepatic metastasis with multiple lymph node metastasis. 4 patients were treated with microwave ablation after intrahepatic metastasis was found. 9 patients were lost to follow-up. Conclusion Laparoscopic treatment of intrahepatic cholangiocarcinoma is safe and feasible in experienced centers.

The prevention and treatment of scars has always been an important task in the field of wound repair.Humans have started treatment for scars long time ago and have created a series of treatments.At the same time,with the development of science and technology,the diagnosis and treatment of scars have made great progress.Through the basic research for new therapeutic targets and innovative of treatment methods,treatment for scar turns more diversified and integrated.As a result,clinicians will suffer many challenges while having more options for scars treatment.Combined with traditional treatment,developing new treatments,and the comprehensive therapy of multiple treatment methods is the mainstream trend of scar treatment.

Objective To explore the differences in autophagic expression levels between hypertrophic scar (HS) tissue and normal skin tissue,and further investigate the relationship between hypertrophic scar formation and autophagy protein expression through the rabbit ear hypertrophic scar model.Methods 30 patients with hypertrophic scar were collected.One hypertrophic scar tissue and one normal skin tissue were harvested.The relative expressions of LC3,P62 and Beclin-1 in each tissue specimen were detected by immunohistochemistry and Western blot.Western blot was used to detect the autophagic-associated protein LC3 (MAPLC3),P62 and Beclin-1 in the hypertrophic scar tissue of rabbit ear and the corresponding normal tissue of rabbit ears at 4 weeks,8 weeks,12 weeks,and 24 weeks,and further explore their clinical significance.Results In vivo,the expression of hypertrophic scar tissue protein LC3 and Beclin-1 was significantly stronger than that in normal skin tissue (P ＜ 0.05).The expression of P62 was significantly weaker than that in normal skin tissue (P ＜ 0.05).In animal experiments,during the process of HS formation,the protein expression of LC3 gradually increased,while the protein expression of P62 gradually decreased;the protein expression of Beclin-1 was higher than that of normal rabbit ears tissue,with statistically significant differences (P ＜ 0.05).Conclusions The expression of LC3 and Beclin-1 in human hypertrophic scar tissues is higher than that in normal tissues.While the expression of P62 is lower than that in normal tissues.That is,the expression of autophagy in human hypertrophic scar tissue showed an upward trend in a certain period of time,and was significantly higher than that in normal tissue.

Objective: To assess the safety and feasibility of the application of the laparoscopic modality in the perioperative treatment of central liver tumors. Methods: Collecting all the clinical information of a total of 40 patients with central liver tumors who received laparoscopic resection treatment carried out at Department of Hepatological Surgery of People′s Hospital of Hunan Provincial from January 2016 to December 2018 to take a retrospective review. There were 19 males and 21 females.The age was (59.5±14.5) years (range: 15 to 71 years) . There were 26 cases of primary hepatic carcinoma (24 cases of hepatocellular carcinoma, 2 cases of cholangiocellular carcinoma) , 8 cases of hepatic cavernous hemangioma, 1 case of metastatic hepatic carcinoma, 5 cases of hepatocellular adenoma. The maximum diameter of tumors were (6.2±2.9) cm (range: 2 to 13 cm) . The patient′s information about hepatectomy methods, blocking mode and time of blood flow, operation time, intraoperative blood loss, intraoperative blood transfusion rate, post-operative hospitalization time, perioperative reoperation and postoperative complications were collected. Results: A total of 40 patients all were treated with laparoscopic surgery. The surgical procedure was as follows: 2 patients received the right hepatic lobectomy (Ⅴ, Ⅵ, Ⅶ and Ⅷ segments) , 2 patients received the left hepatic lobectomy (Ⅱ, III and Ⅳ segments) , 13 patients received mesohepatectomy (Ⅳ, Ⅰ and Ⅷ segments) , 2 patients received left hepatic trisegmentectomy (Ⅱ, Ⅲ, Ⅳ and Ⅷ segments) , 2 patients received right hepatic trisegmentectomy (Ⅳ, Ⅴ, Ⅵ, Ⅶ and Ⅷ segments) , 7 patients received Ⅷ segmentectomy, 1 patient received Ⅳ segmentectomy, 3 patients received Ⅴ and Ⅷ segmentectomy, 5 patients received hepatic caudate lobe resection (Ⅰ, Ⅸ segments) , and 3 patients received local tumors resection.Pathological results: there were 26 cases of primary hepatic carcinoma (24 cases of hepatocellular carcinoma, 2 cases of cholangiocellular carcinoma) , 8 cases of hepatic cavernous hemangioma, 1 case of metastatic hepatic carcinoma, 5 cases of hepatocellular adenoma; the pathological reports of all malignant tumor cases all showed negative incisal edge. The operative time was (333±30) minutes (range: 280 to 380 minutes) ; the intraoperative hepatic portal occlusion period was (58±13) minutes (range: 30 to 90 minutes) ; the intraoperative hemorrhage was (173±129) ml (range: 20 to 600 ml) ; the intraoperative blood transfusion rate was 2.5% (1/40) ; the postoperative incidence of bile leakage was 2.5% (1/40) , the hospital discharge of 1 patient with bile leakage was approved after conservative treatments like T pipe decompression and adequate drainage; there was 1 case of abdominal infection and 1 case of pulmonary infection, both of which were discharged from the hospital with conservative treatments; there were no other serious postoperative complications. The postoperative hospital stay was (10.7±2.7) days (range: 6 to 16 days) ; there were no perioperative mortality and reoperation cases. Conclusion In the centers with abundant laparoscopic hepatectomy experiences, the laparoscopic resection is proved to be safe and feasible in the perioperative treatments of central liver tumors by the highly selective cases, the adequate preoperative assessment and reasonable surgical techniques and approach.