OBJECTIVE: To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout. METHODS: The Sidt2 knockout (Sidt2^-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed. RESULTS: Sidt2^-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2^-/- HL7702 cells. CONCLUSION Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.
Humans ; Lysosome-Associated Membrane Glycoproteins/metabolism* ; Autophagy ; Apoptosis ; Hepatocytes ; Lysosomes/metabolism* ; Chloroquine/pharmacology* ; Nucleotide Transport Proteins/metabolism*

Objective To analyze the reasons of gastrointestinal function recovery related to postoperative esophagogastric fistula and the roles of the Xiaochengqi decoction by enema and jejunal nutrition tube on gastrointestinal function recovery.Method Clinical data of 1 patient with esophagogastric anastomotic fistula after gastric stromal tumors(GST)resection on March 16,2022 was retrospectively analyzed,to observe the influence of Traditional Chinese Medicine in postoperative recovery.Results The patient,a 77-year-old male,underwent laparoscopic proximal gastrectomy and esophagogastrostomy on March 16,2022 due to cardia tumor.Seven days after surgery,there was some turbid matter in the abdominal drain tube,severe pain on upper abdomindal occurred after digestive tract radiography,it was indicated that anastomotic fistula was existed.After intragastric administration and nasal feeding of Xiaochengqi decoction,anus ventilates and defecates much mushy stool on the 15th day after postoperative esophagogastric fistula.On the 21st day after fistula,Buzhongyiqi and Xiaochengqi decoction was applied by nasointestinal feeding tube.On the 47th day,the patient got out of bed and stood,the stools were out by enema.On the 58th day after surgery,the digestive tract radiography indicated there was not any contrast media overflow near the fistula and contrast media could get through the duodenum smoothly.Anastomotic stricture.After tube extraction,a liquid diet is fed,formed stool is defecated without abdominal distension and pain.On the 63rd day after surgery,the patient is discharged from hospital.Conclusions It is advantageous for the recovery of gastrointestinal function by enema and jejunal nutrition tube feeding of Xiaochengqi decoction.It shortens the anal exhaust time,fastens the recovery of gastrointestinal function,improves health status,promotes healing,and shortens the length of stay.

Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.

Objective:To evaluate the effectiveness of perioperative fasting abbreviation in traumatic patients with orthopaedic trauma and diabetes mellitus undergoing selective surgery.Methods:The patients were selected for this prospective nonrandomized controlled study who had undergone selective surgery from June 2019 to June 2021 at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital. They were divided into an intervention group and a control group according to the wards where they stayed. The intervention group was fasted for solids from 0 o'clock on the surgery day and received oral solution with 6.25% maltodextrin which had been prepared by the nutritional department 3 hours prior to surgery. The control group was fasted for either liquids or solids from the midnight before surgery. All patients were evaluated according to the wake-up score and defensive reflex score after surgery. Once they were awakened, they were allowed slag-free drinks. Normal food was allowed if there was no discomfort after 2 hours. The 2 groups were compared in terms of basic information, actual preoperative fasting time, total amount of preoperative drinking, and postoperative time for initial drinking and eating. The perioperative subjective feelings (anxiety, thirst, hunger, nausea, fatigue, dizziness, sweating, stomach discomfort, etc.), grip strength and blood glucose were observed and compared between the 2 groups. Adverse reactions in the 2 groups were also observed.Results:A total of 135 patients were included, including 52 in the intervention group and 83 in the control group. The intervention group consisted of 22 males and 30 females aged from 30 to 84 years; the control group consisted of 39 males and 44 females aged from 29 to 81 years. There was no significant difference in the basic information between the 2 groups, showing comparability ( P>0.05). The intervention group had significantly shorter preoperative fasting time [3.5 (2.5, 6.3) h versus 12.0 (9.0, 16.0) h], significantly higher water intake before surgery [300 (200, 300) mL versus 100 (100, 200) mL], significantly shorter postoperative fasting time [0.08 (0, 1.25) h versus 2.00(0, 6.00) h], and significantly reduced time to return to normal diet [2.0 (2.0, 2.3) h versus 3.0(2.0, 6.0) h] than the control group (all P<0.05). The symptoms of anxiety, fatigue, sweating, and stomach discomfort in the intervention group were significantly fewer than those in the control group throughout the evaluation period. The thirst in the intervention group was significantly alleviated than that in the control group immediately after returning to the ward after surgery, and the dizziness and hunger were significantly alleviated than those in the control group when the patients left the ward to the operation room before surgery and immediately after returning to the ward. The symptom of nausea after returning to normal diet in the intervention group was significantly relieved compared with the control group. All the comparisons above showed statistically significant differences ( P<0.05). The blood glucose in the intervention group 2 hours after taking slag-free drinks was significantly higher than that in the control group ( Z=-2.108, P=0.035). There was no significant difference in the blood glucose between the 2 groups during other measurement periods ( P>0.05). There were no serious adverse reactions in either of the 2 groups. Conclusion:The protocol of perioperative fasting abbreviation may be safe and feasible for the patients with orthopaedic trauma and diabetes mellitus undergoing selective surgery, because it shows benefits of improving the patients' subjective feelings and stabilizing the blood glucose perioperatively.

Objective:To explore the prognostic influencing factors of adult lymphoma-associated hemophagocytic syndrome (LAHS) based on multicenter data.Methods:The clinical data of 86 LAHS patients diagnosed in 9 medical centers of Huaihai Lymphoma Working Group from January 2015 to August 2020 were retrospectively analyzed. The optimal cut-off value of continuous variables was obtained based on MaxStat algorithm. Cox proportional hazard regression model was used for univariate and multivariate analyses. Kaplan-Meier method was used for survival analysis, and log-rank test was performed.Results:Among the 86 adult LAHS patients, 50 (58.1%) were males and 36 (41.9%) were females, the median age of the patients was 57 years old (19-76 years old), and the median overall survival (OS) time was 1.67 months (95% CI 0.09- 3.24 months). The most common pathologic type was diffuse large B-cell lymphoma (58 cases, 67.44%). Based on MaxStat algorithm, the optimal cut-off values of age, albumin, serum creatinine, lactate dehydrogenase, fibrinogen and platelet count were 64 years old, 30.1 g/L, 67 μmol/L, 1 045 U/L, 4.58 g/L and 72×10 9/L, respectively. Multivariate analysis showed that patient's age, lactate dehydrogenase, albumin and fibrinogen levels were independent influencing factors for OS (all P < 0.05). Conclusions:LAHS is dangerous and progresses quickly. Patients with age ≥ 64 years old, lactate dehydrogenase ≥ 1 045 U/L, fibrinogen ≥ 4.58 g/L and albumin < 30.1 g/L have poor survival.

Objective:Factors influencing the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults were analyzed based on multicentric data.Methods:Clinical data of 124 adult patients with HLH diagnosed in eight medical centers in the Huaihai Lymphoma Working Group from March 2014 to July 2020 were collected. The optimal truncation value of continuous variables was obtained based on the Maxstat algorithm, X-Tile software, and restricted cubic spline. Cox proportional risk regression model was used to construct the adult HLH risk prediction model, and the visualization of the model was realized through the histogram. The bootstrap resampling method was used to verify the model, C-index and calibration curve was used to verify the histogram, and the prediction accuracy was checked. Kaplan-Meier analysis was used to calculate the survival rate and draw the survival curve. Furthermore, the differences between groups were tested by log-rank.Results:The median age of the 124 patients was 55 (18-84) years, including 61 (49.19%) males. The most common etiology was infection. Serum ferritin increased in 110 cases (88.71%) , hepatosplenomegaly in 57 cases (45.97%) . Of the 124 patients, 77 (62.10%) died, and the median survival time of the patients was 7.07 months. Univariate results showed that the prognosis of adult HLH was influenced by sex, age, fibrinogen, serum creatinine, alanine aminotransferase, and albumin ( P<0.05) . The results of multivariate analysis showed that gender, platelet, albumin, alanine aminotransferase, and treatment regimens were independent influencing factors for prognosis. Based on the above five risk factors, the prediction model of the histogram was established, and the C-index of the model was 0.739. Finally, the calibration chart showed good consistency between the observed and predicted values of HLH. Conclusion:The prognosis of the adult hemophagocytic syndrome is influenced by many factors. Gender, platelet, albumin, alanine aminotransferase, and treatment regimens are independent risk factors. Therefore, the established histogram provides a visual tool for clinicians to evaluate the prognosis of adult HLH.

Background and purpose:Non-small cell lung cancer (NSCLC) patients who have good curative effect on epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) will inevitably acquired drug resistance. It will effect the survival directly. In contrast, few studies have found that EGFR-TKI effectively acquired drug resistance in patients with clinical characteristics. We investigated clinical characteristics of NSCLC patients who experienced acquired drug resistance during geiftinib therapy. Methods:To review the treatment from the beneift of patients with non-small cell lung cancer. All of the data were obtained from Jan. 2007 to Jan. 2014 in Xinjiang tumor hospital. The treatment for failure of acquired drug resistance of clinical manifestations, time to progress (TTP) and post-progression survival (PPS) were retrospectively analyzed. Results:The total collection of 417 patients. Median TTP was 10.2 months (95%CI:9.5-10.9). The TTP of women adenocarcinoma patients who didn’t smoke signiifcantly extended. When acquired drug resistance happened, 63.3%of patients appeared worse symptoms. The progress of the disease is as follows:209 cases (58.4%) from the primary lesion, 137 cases (38.3%) before the transfer, 194 cases (54.2%) of new happened. Patients of epidermal growth factor receptor (EGFR) wild type had more tendencies of symptomatic deterioration and new central nervous system (CNS) transfer than patients of EGFR mutation type. Patients of exon 19 deletion and L858R mutations on the new transfer were different (41.4%vs 6.3%, P=0.02). PPS was 8.9 months (95%CI:7.4-10.4). Smoking history, performance status (PS) score, new CNS lesions and the subsequent chemotherapy is independent factors of PPS. Conclusion:This study suggests that the clinical manifestations of acquired drug resistance according to EGFR mutation status and EGFR mutation genotype may be different. In addition, after the treatment of acquired drug resistance in patients with non-small cell lung cancer, the subsequent clinical beneift from chemotherapy are also associated with PPS.

Inrecentyears,somecardiovascularguidelineshavegradualyintroducedambulatory blood pressure monitoring ( ABPM ) as an indispensable means for better diagnosis and management of hypertensive patients. ABPM can more comprehensively provide 3 types of information that has potential clinical value:the assessment of real or mean blood pressure level, the diurnal rhythm of blood pressure, and the blood pressure variability. This article review s the roles of ABPM in the outcome assessment in patients w ith acute ischemic stroke.

Objective To analyze the MRI characteristics of vestibulocochlea neurovascular compression in patients with vestibular paroxysmia (VP) and to investigate the effect of the compression,its site and degree,on the occurrence of VP.Methods Twenty-eight cases of VP (VP group) and 28 cases of vertiginous patients other than VP (control group) were retrospectively reviewed.Three dimensional magnetic resonance angiography (3D-MRA) was performed and the data were used for neurovascular crosscompression (NVCC) analysis.The frequency and type of NVCC,the origin of the offending vessel and the distance between compression site and brainstem were compared between the two groups.Results The frequency of NVCC was 96.4％ (27/28) in VP group,with a significant difference compared with control group (13/28,46.4％ ;x2 =17.15,P ＜0.01).The most common NVCC type was vascular loop compression at vestibulocochlear nerve (15/35,42.9％).Anterior inferior cerebellar artery was the most common offending vessel (25/35,71.4％) in VP group.There were no significant differences between the two groups in the type of NVCC or the origin of the offending vessel.The frequency on the distortion and (or) displacement of vestibulocochlear nerve which was severely compressed by vessel in VP group (7/56,12.5％) was significantly higher than that in control group (0; P =0.013).The distance between compression site and brainstem was (8.57 ± 5.08) mm in VP group,and (8.93 ± 4.64) mm in control group,showing no significant difference.The ratio that the distance was less than 15 mm between compression site and brainstem in unilateral NVCC of VP group (100％) was significantly higher than unilateral NVCC of control group (7/10,P =0.033).Conclusions The VP patients have higher NVCC incidence and the most common NVCC type is vascular loop compression at vestibulocochlear nerve which is mainly caused by anterior inferior cerebellar artery.NVCC in VP patients mostly occurs in the central myelin portion of vestibulocochlear nerve.The site and degree of neurovascular compression may relate to the occurrence of VP.

Objective To explore the characteristics of epidermal growth factor receptor (EGFR)mutation in patients with lung adenocarcinoma in Xinjiang automonous region.Methods 181 patients with lung adenocarcinoma were collected (Uighur:71 cases;Han:105 cases).The clinical characteristics of each patient was recorded,and the paraffin embedded tumor tissue was col-lected.Exons 18~21 of EGFR genes were detected by ARMs.The mutation rates of EGFR genes were compared in Uyghur and Han nationalities,and the relationship between EGFR gene muta-tions and clinical ccharacteristics were analyzed.Results EGFR mutation rate was 32.6% in all patients ,in which the mutations rate in Han patients (4 5 .7 % )was higher than Uyghur patients (15.8%).The main mutation types were the deletion of exon 19 and L858R of exon 21.The dele-tion of exon 19 was more common in Uyghur patients.In Han patients,EGFR mutation was relat-ed to the gender,smoking history and the differentiated degree of tumors,whereas Uyghur patients was only associated with smoking history.Conclusion For Uyghur patients,EGFR mutation rate is lower than Han patients in the same area,and exon 19 sensitive mutation is more frequent.