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 discuss the relationship between activated glia cells in distal segment of the spinal cord and widespread pain.Methods Fifty female rats were randomly divided into sham group,the chronic constriction injury of the infraorbital nerve(CCI-ION)group,CCI-ION+minocycline(Mino)group,CCI-ION+L-2-aminoadipic acid(LAA)group,and CCI-ION+normal saline(NS)group,n=10 for each group.CCI-ION model was established and Mino,LAA,and normal saline were delivered intrathecally to CCI-ION rats.Immunofluorescence staining was used to detect activated astrocytes and microglia in the medulla oblongata,cervical,thoracic,and lumbar spinal cord segments.On the 7th,14th,21st,28th day,von Frey filaments were used to evaluate the mechanical withdrawal threshold of vibrissa pad,and electronic von Frey tactile pain meter was used to measure the mechanical withdrawal threshold of front paw,chest and hind paw.The radiant thermal stimulator was used to measure the thermal withdrawal threshold of hind paw.Results After intrathecal injection of Mino to inhibit microglia,the activated microglia in each spinal cord segment decreased.Moreover,inhibiting astrocytes by using LAA significantly reduced activated astrocytes in spinal dorsal horn from distal segments.Behavioral assay showed that after intrathecal injection of Mino and LAA,the mechanical allodynia of vibrissa pad in CCI-ION rats was relieved.However,there was no significant difference(P>0.05)in the thermal and mechanical withdrawal thresholds in the hind paw of CCI-ION rats after intrathecal injection of Mino,while intrathecal injection of LAA significantly increased the thermal and mechanical withdrawal thresholds in the hind paw,indicating the relief of widespread pain induced by CCI-ION.Conclusion The activated astrocytes in distal segments of the spinal cord mediated CCI-ION-induced widespread pain.

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.

Objectives: To investigate the clinical application effect of a quantitative method of atlantoaxial reduction angle in basilar invagination. Methods: A retrospective analysis of clinical and radiographic data was conducted of 38 patients with complicated atlantoaxial dislocation and basilar invagination admitted to the Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University from May 2020 to May 2022. There were 5 males and 33 females, aged (53.5±9.9) years (range: 38 to 80 years). All patients underwent C_1-2 interarticular fusion cage implantation+occipital-cervical fixation by pressing rob with the cantilever technique. The atlantoaxial reduction model of previous studies by our team was used to calculate the reduction angles before surgery. Then titanium rods of prebending angle were prepared according to the calculation before the operation. After that quantitative reduction of angle was performed during the operation. The paired t-test was used to compare the difference between the theoretical and actual reset value. Results: The theoretical reduction angle of all patients was (10.62±1.78)° (range: 6.40° to 13.20°), the actual reduction angle was (10.53±1.63)° (range: 6.70° to 13.30°) and there was no statistical difference between them (t=1.688, P=0.100). The theoretical posterior occipitocervical angle after the operation of all patients was (117.37±5.88)° (range: 107.00° to 133.00°), the actual posterior occipitocervical angle after the operation was (118.25±6.77)° (range: 105.40° to 135.80°) and there was no statistical difference between them (t=-0.737, P=0.466). The postoperative follow-up time of the patients was more than 6 months and the symptoms of all patients were relieved. All patients had satisfactory fusion between small joints without incision infection, internal fixation fracture, displacement, atlantoaxial redislocation, and other long-term complications. Conclusion: The quantitative method of atlantoaxial reduction angle in basilar invagination can calculate the theoretical reduction angle of the clivus axis angle and guide the preparation of the pre-bending titanium rod before surgery, so as to realize the quantification of the atlantoaxial reduction angle.

In this study, the mechanism of Xiaoyan Lidan formula (XYLDF) against 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC)-induced chronic intrahepatic cholestasis (CIHC) in mice was investigated based on metabolomics, molecular docking and pharmacological methods. In the pharmacodynamics study, a dosage of 5 g·kg^-1 (clinical equivalent) XYLDF was administered in DDC-induced mice, then the effect of XYLDF against CIHC was evaluated by measuring the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) as well as total bilirubin (TBIL) in serum and observing liver histopathological changes. All experiments were approved by the Ethical Committee Experimental Animal Center of Guangzhou University of Chinese Medicine (ZYD-2021-001). The serum metabolites of mice in each group were detected and identified based on ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, and the relevant biological pathways and molecular key targets were further enriched. Molecular docking technology was used to further evaluate the binding activity of the main active ingredients of XYLDF with potential targets. Subsequently, the in vitro experiment was conducted for the validation of the vital target. The results showed that compared with the model group, XYLDF significantly decreased the levels of ALT, AST, AKP and TBIL in the serum of CIHC mice, as well as alleviated inflammatory infiltration and hepatocyte necrosis in liver tissue. According to the metabonomic study, a total of 35 differential metabolites was identified as biomarkers associated with cholestasis, 12 of which were significantly recovered by XYLDF treatment. These biomarkers were involved in the pathways of primary bile acid biosynthesis and linoleic metabolism, which are closely related to the mechanism of XYLDF against CIHC. Protein-protein interaction network indicated that cytochrome P450 3A4 (CYP3A4) and cytochrome P450 1A1 (CYP1A1) are significant potential targets with good binding properties with six major active ingredients of XYLDF. Furthermore, it was found that 4-methoxy-5-hydroxycanthin-6-one, dehydroandrographolide and isodocarpin, three of the main active components in XYLDF, markedly induced the expression of CYP3A4 mRNA in vitro. This study revealed that XYLDF mainly mediates the biosynthesis of bile acids in CIHC mice to improve liver tissue lesions and bile efflux disorders, among which, CYP3A4 is the key target in the protection of XYLDF against CIHC. This research provides a reference for further elucidation of the pharmacological mechanism of XYLDF.

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