Objective To explore the effect of preoperative administration of glycopyrronium bromide on postoperative cognitive dysfunction(POCD)in elderly patients undergoing laparoscopic inguinal hernia repair surgery.Methods 74 elderly patients underwent laparoscopic inguinal hernia repair surgery under general anesthesia with a laryngeal mask were randomly divided into control group(group C,25 cases),low-dose glycopyrronium bromide group(0.2 mg,group L,24 cases),medium-dose glycopyrronium bromide group(0.4 mg,group M,25 cases).Blood was collected from patients 1 d before surgery and 3 d after surgery,and serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),brain function related factors[5-hydroxytryptamine(5-HT),brain-derived neurotrophic factor(BDMF)]were measured by enzyme linked immunosorbent assay(ELISA).The Montreal Cognitive Assessment Scale(MoCA)was used to assess the cognitive function of the patients.Airway secretion scores,the incidence of arrhythmia,dry mouth and dysuria were recorded.Results There was no significant difference in the incidence of POCD among the three groups of patients(P＞0.05);At 3 d postoperatively,5-HT and BDNF levels in group L were higher than those in group C,the BDNF level in group L was higher than that in group M,there were statistically significant(P＜0.05);At 3 days after surgery,the levels of serum IL-1β,IL-6 and TNF-α in group C were significantly higher than those at 1 day before surgery(P＜0.05),the levels of serum IL-6 and TNF-α in group M were significantly higher than those at 1 day before surgery(P＜0.05),there were no significant differences in the levels of serum IL-1β,IL-6 and TNF-α in group L compared with those at 1 day before surgery(P＞0.05),there were no significant differences in the levels of serum IL-1β,IL-6 and TNF-α among the three groups at 3 days after surgery(P＞0.05);Postoperative airway secretion was significantly reduced in group L and group M compared with group C(P＜0.05),and there was no significant difference between group L and group M(P＞0.05).The incidence of adverse reactions(dry mouth and dysuria)in group M was significantly higher than that in group L and group C(P＜0.05).Conclusion Low-dose(0.2 mg)glycopyrronium bromide is more appropriately recommended as a preoperative medication for elderly patients undergoing laparoscopic inguinal hernia repair surgery,and increased dosage is associated with an increase in adverse reactions and POCD.

Objective:To establish a mesenchymal stem cell(MSC)-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease(aGVHD).Methods:Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors,and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients.The recipient mouse received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1× 107/mouse)in 6-8 hours post irradiation to establish a bone marrow transplantation(BMT)mouse model(n=20).In addition,the recipient mice received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1 × 107/mouse)and spleen lymphocytes(2 × 106/mouse)in 6-8 hours post irradiation to establish a mouse aGVHD model(n=20).On the day 7 after modeling,the recipient mice were anesthetized and the blood was harvested post eyeball enucleation.The serum was collected by centrifugation.Mouse MSCs were isolated and cultured with the addition of 2％,5％,and 10％recipient serum from BMT group or aGVHD group respectively.The colony-forming unit-fibroblast(CFU-F)experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC.The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining.In addition,the expression of self-renewal-related genes including Oct-4,Sox-2,and Nanog in MSC was detected by real-time fluorescence quantitative PCR(RT-qPCR).Results:We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD.CFU-F assay showed that,on day 7 after the culture,compared with the BMT group,MSC colony formation ability of aGVHD serum concentrations groups of 2％and 5％was significantly reduced(P＜0.05);after the culture,at day 14,compared with the BMT group,MSC colony formation ability in different aGVHD serum concentration was significantly reduced(P＜0.05).The immunofluorescence staining showed that,compared with the BMT group,the proportion of MSC surface molecules CD29+and CD 105+cells was significantly dereased in the aGVHD serum concentration group(P＜0.05),the most significant difference was at a serum concentration of 10％(P＜0.001,P＜0.01).The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4,Sox-2,and Nanog was decreased,the most significant difference was observed at an aGVHD serum concentration of 10％(P＜0.01,P＜0.001,P＜0.001).Conclusion:By co-culturing different concentrations of mouse aGVHD serum and mouse MSC,we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability,which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5％.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P＜0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P＞0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.

Objective To explore the characteristics of myocardial injury in patients with acute myocardial infarction(AMI)complicated by pleural effusion and its effect on long-term prognosis.Methods It was a prospective single-center study.Patients with AMI who were admitted to hospital within 15 days from symptom onset and performed echocardiography and cardiac magnetic resonance imaging(CMR)during hospitalization were consecutively enrolled and assigned to the with-pleural effusion group and the without-pleural effusion group according to the echocardiography result.Baseline data,cardiac magnetic resonance myocardial injury index and echocardiography characteristics were compared between the two groups.The occurrence of major adverse cardiovascular and cerebrovascular events(MACCE)was recorded through outpatient follow-up and telephone follow-up,including all-cause death,re-infarction,revascularization,rehospitalization for congestive heart failure and stroke.Cox regression analysis was performed to analyze influencing factors of all-cause death.Results Among 211 patients,31(14.7%)patients had pleural effusion and 180(85.3%)had no pleural effusion.Compared with the group without pleural effusion,the left ventricular end-diastolic diameter was larger,and left ventricular ejection fraction assessed by echocardiography was lower in the group with pleural effusion(P＜0.05).There were no significant differences in infarct size,left ventricular end-diastolic volume,left ventricular end-systolic volume,left ventricular ejection fraction and the presence of microvascular obstruction and intramyocardial hemorrhage between the two groups in CMR(all P＞0.05).At a median follow-up of 31 months,MACCE occurred in 43(20.4%)patients,and there was no significant difference between the two groups(χ2=3.160,P=0.075).Six cases(2.8%)had all-cause death.The incidence of all-cause death was higher in the group with pleural effusion than that in the group without pleural effusion(9.7%vs.1.7%,P<0.05).There was no significant difference in the incidence of other adverse events between the two groups(P＞0.05).Multivariate Cox regression analysis showed that advanced age and presence of pleural effusion were independent risk factors of all-cause death during follow-up.Conclusion Patients with AMI combined with pleural effusion have more severe myocardial injury and higher all-cause mortality.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is widely used for targeted genomic and epigenomic modifications, transcriptional regulation and real-time cell imaging, and has already demonstrated great potential for applications in agriculture, industry and medicine. The promise of the technology depends upon the five intrinsic properties of CRISPR/Cas: targeting, target unwinding, target cutting, target residence, and collateral cleavage. Here, mainly using Streptococcus pyogenes CRISPR/Cas9 as example, we will focus on the target residence of CRISPR/Cas in applications of the CRISPR/Cas technology, summarize the recent progress, and discuss the effect of CRISPR/Cas target binding and residence on DNA double strand break repair pathway choices and the opportunities that CRISPR/Cas target residence presents to optimize the CRISPR/Cas technology.

Objective To investigate the application effect of external treatment method of Xingqi Huoxue Zhitong Paste in the treatment of phlebitis. Methods Using mannitol as an inflammatory agent, a phlebitis model was established by infusion into the ear marginal vein of rabbits. Successfully modeled rabbits were randomly divided into four subgroups for intervention, while the blank control group was routinely raised without any intervention. After the intervention, the improvement effect of Xingqi Huoxue Zhitong Paste on mannitol-induced transfusion-induced phlebitis in rabbits was explored by observing the manifestations of phlebitis, serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor A (VEGF-A) levels. Results The success rate was up to 90.0%. On the first day of treatment, there were 8 ineffective cases and 1 effective case in the saline group; 6 ineffective cases and 3 effective cases in the hirudoid group; 7 ineffective cases and 2 effective cases in the magnesium sulfate group; 7 ineffective cases and 2 effective cases in the Xingqi Huoxue Zhitong Paste group. There was no significant difference in the curative effect among the four groups (P=0.431). On the fourth day of treatment, there were 5 ineffective cases, 2 effective cases, and 2 markedly effective cases in the saline group; 1 effective case, 5 markedly effective cases, and 3 cured cases in the hirudoid group; 2 effective cases, 5 markedly effective cases, and 2 cured cases in the magnesium sulfate group; 2 effective cases, 4 markedly effective cases, and 3 cured cases in the Xingqi Huoxue Zhitong Paste group. On the fourth day of treatment, compared with the saline group, the curative effects of the hirudoid group (P=0.001), the magnesium sulfate group (P=0.020), and the Xingqi Huoxue Zhitong Paste group (P=0.003) were statistically significant. There was no significant difference in curative effect in the magnesium sulfate group and the Xingqi Huoxue Zhitong Paste group when compared with the hirudoid group (P>0.05); there was no significant difference in curative effect in the Hirudoid group and the Xingqi Huoxue Zhitong Paste group when compared with the magnesium sulfate group (P>0.05); there was no significant difference in curative effect in the hirudoid group and the magnesium sulfate group when compared with the Xingqi Huoxue Zhitong Paste group (P>0.05). The effective rate of the saline group was 11.1%, and the cure rate was 0%. The effective rate of the hirudoid group was 100.0%, and the cure rate was 33.3%. The effective rate of the magnesium sulfate group was 77.7%, and the cure rate was 44.4%. The effective rate of the Xingqi Huoxue Zhitong Paste group was 66.7%, and the cure rate was 22.2%. The drug effectiveness of the Xingqi Huoxue Zhitong Paste group, the hirudoid group, and the magnesium sulfate group was higher than that of the saline group (P < 0.05). After the intervention, the levels of serum inflammatory factors IL-6, TNF-α, and VEGF-A in the four model subgroups were statistically significant compared with the blank control group (P < 0.05). The levels of serum inflammatory factors IL-6, TNF-α, and VEGF-A in the saline group showed significant difference from those in the hirudoid group, the magnesium sulfate group, and the Xingqi Huoxue Zhitong Paste group (P < 0.05). Compared with the hirudoid group, the differences in serum inflammatory factors IL-6, TNF-α, and VEGF-A contents in the magnesium sulfate group and the Xingqi Huoxue Zhitong Paste group were statistically significant (P < 0.05). The inflammatory factor levels in the blank control group were the lowest, while those in the normal saline group were the highest. Conclusion Xingqi Huoxue Zhitong Paste group has an improving effect on mannitol-induced infusion phlebitis in rabbits, but its efficacy is inferior to that of the commonly used hirudoid ointment. Therefore, appropriate adjustments and improvements can be made to the drug formula to enhance its effectiveness.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Humans ; Anemia, Aplastic ; Hemoglobinuria, Paroxysmal/complications* ; Syndrome

Objective: To summarize the clinical data and prognosis of children with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) common genes. Methods: This was a retrospective cohort study.Clinical data of 56 children with Ph-like ALL common gene cases (Ph-like ALL positive group) treated from January 2017 to January 2022 in the First Affiliated Hospital of Zhengzhou University, Henan Children's Hospital, Henan Cancer's Hospital and Henan Provincial People's Hospital were collected, 69 children with other high-risk B cell acute lymphoblastic leukemia (B-ALL) at the same time and the same age were selected as the negative group. The clinical characteristics and prognosis of two groups were analyzed retrospectively. Comparisons between groups were performed using Mann-Whitney U test and χ² test. Kaplan-Meier method was used for survival curve, Log-Rank test was used for univariate analysis, and the Cox regression model was used for multivariate prognosis analysis. Results: Among 56 Ph-like ALL positive patients, there were 30 males and 26 females, and 15 cases were over 10 years old. There were 69 patients in Ph-like ALL negative group. Compared with the negative group, the children in positive group were older (6.4 (4.2, 11.2) vs. 4.7 (2.8, 8.4) years), and hyperleukocytosis (≥50×10⁹/L) was more common (25% (14/56) vs. 9% (6/69)), the differences were statistically significant (both P<0.05). In the Ph-like ALL positive group, 32 cases were positive for IK6 (1 case was co-expressed with IK6 and EBF1-PDGFRB), 24 cases were IK6-negative, of which 9 cases were CRLF2 positive (including 2 cases with P2RY8-CRLF2, 7 cases with CRLF2 high expression), 5 cases were PDGFRB rearrangement, 4 cases were ABL1 rearrangement, 4 cases were JAK2 rearrangement, 1 case was ABL2 rearrangement and 1 case was EPOR rearrangement. The follow-up time of Ph-like ALL positive group was 22 (12, 40) months, and 32 (20, 45) months for negative group. The 3-year overall survival (OS) rate of positive group was significantly lower than the negative group ((72±7) % vs. (86±5) %, χ²=4.59, P<0.05). Compared with the 24 IK6-negative patients, the 3-year event free survival (EFS) rate of 32 IK6 positive patients was higher, the difference was statistically significant ((88±9) % vs. (65±14) %, χ²=5.37, P<0.05). Multivariate Cox regression analysis showed that the bone marrow minimal residual disease (MRD) not turning negative at the end of first induction (HR=4.12, 95%CI 1.13-15.03) independent prognostic risk factor for patient with Ph-like ALL common genes. Conclusions: Children with Ph-like ALL common genes were older than other high-risk B-ALL patients at diagnosis, with high white blood cells and lower survival rate. The bone marrow MRD not turning negative at the end of first induction were independent prognostic risk factor for children with Ph-like ALL common gene.
Male ; Female ; Humans ; Child ; Prognosis ; Philadelphia Chromosome ; Retrospective Studies ; Receptor, Platelet-Derived Growth Factor beta/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Neoplasm, Residual