AIM:To investigate whether the cigarette smoke extract (CSE) causes senescence of C2C12 myo-blasts and the relationship between senescence and histone deacetylase 2(HDAC2).METHODS: Murine C2C12 cells were induced to differentiate into myoblasts.The HDAC2 activator and inhibitor were used to investigate the effects of CSE in the myoblasts on cell senescence and the expression of HDAC2.The expression of HDAC2 at mRNA and protein levels was determined by real-time PCR and Western blot, respectively, and the positive cell rate of β-galactosidase staining for cell senescence was also detected.RESULTS:The optimal concentration of CSE was 60 mL/L and the intervention time was 24 h.After the intervention of CSE, the positive cell rate ofβ-galactosidase staining was increased, accompanied with the reduction of HDAC2 expression at mRNA and protein levels.The expression of HDAC2 at mRNA and protein levels was increased by 4, 5, 6, 7-tetrabromobenzotriazole (TBB), accompanied with the reduction of positive cell rate ofβ-galacto-sidase staining.Furthermore, when HDAC2 expression at mRNA and protein levels was reduced by HDAC2 inhibitor valp-roic acid, the positive cell rate of β-galactosidase staining was increased.CONCLUSION: CSE promotes the senescence by reducing the expression of HDAC2 in C2C12 myoblasts.

Objective To investigate the efficacy of the combination of bone marrow stromal cells (BMSCs) and bcl-2 gene in the treatment cerebral ischemia taxi its effect on the expression of basic fibroblast growth factor (bFGF) in rats.Methods Forty Wistar rats were used to establish middle cerebral artery occlusion model. They were randomly divided into 4 groups: saline control, bcl-2, BMSCs and BMSCs + bcl-2 groups (n = 10 in each group). Every group was redivided into 3- and 14-day after reperfusion subgroups (n = 5 in each subgroup). Neurological scores of the experimental rats were assessed. BMSCs were labeled with bromodeoxyuridine (BrdU). The distribution and numbers of BMSCs, the expressions of Bcl-2 and bFGF were detected by immunohistochemistry, and apoptotic cells were detected with TUNEL staining in rat brain. Results The neurological score at day 3 after reperfusion in the BMSCs + bcl-2 group was significantly lower than that in the saline control group (P < 0. 05), and at day 14, it was significantly lower than that in the other 3 groups (all P <0. 05). A large number of BrdU-positive BMSCs were observed in the infarcted hemisphere in the BMSCs + bcl-2 and BMSCs groups. The numbers of BrdU-positive BMSCs at day 3 and 14 after reperfusion in the BMSCs + bcl-2 group were significantly higher than those in the BMSCs group (all P <0. 05). The expressions of Bcl-2 in the infarcted hemisphere at day 3 and 14 after reperfusion in BMSCs +hel-2 group wre significantly higher than those in the other 3 groups (all P <0. 05). The expressions of Bcl-2 at all time points were increased more significantly than those in the other 3 groups (all P <0. 05). The numbers of apoptosis in brain at all time points in the BMSCs + bcl-2 group were decreased more significantly than those in the other 3 groups (all P <0. 05). Conclusions Both BMSCs and bcl-2 genes have the therapeutic effect on cerebral ischemia. The efficacy of combination of both ,of them is significantly superior to monotherapy. They may significantly improve the neurological function and increase the expression of bFGF in rats. Its mechanism may be that bcl-2 genes have inhibited BMSCs apoptosis at the same time of anti-apoptosis in brain.

Objective:To analyze one case of delayed diarrhea caused by irinotecan. Methods:The pathogeny, mechanism, ge-netics and treatment of the case were analyzed. Results:Delayed diarrhea was the dose-limited toxicity of irinotecan, which was related with the cytotoxicity of the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Genetic polymorphism was one of important risk factors, especially UGT1A1 polymorphisms could be used as a predictor for the diarrhea. The pharmacotherapy of the diarrhea was ef-fective and rational, and the clinical pharmacist provided rational pharmaceutical care for the patient. Conclusion:It is very important to enhance pharmaceutical care for the patients treated with irinotecan.

Objective To prepare a novel ultrasound contrast agent , targeted phase-shift lipid nanoparticles mediated by tumor homing and penetrating peptide tLyP-1 ,and to evaluate its characteristics . Methods The nanoparticles were prepared by filming-rehydration and acoustic-vibration methods .The morphology ,distribution ,particle size and zeta potential were detected . After heating and irradiating of low intensity focused ultrasound ( LIFU) ,the phase-shift characteristic and the enhancement effect in vitro were observed . The tumor homing and cell-penetrating properties of the nanoparticles were examined by confocal laser scanning microscopy and flow cytometry . The cytotoxicity of the nanoparticles was evaluated by CCK 8 assay . Results The size and distribution of nanoparticles were uniformed . The size and zeta potential of nanoparticles were ( 399 .50 ± 29 .98) nm and ( 3 .28 ± 1 .72) mV ,respectively . When the nanoparticles were heated to a temperature of 45 ℃ or after irradiated by LIFU ,nanoparticles generated phase-shift and enhanced ultrasound imaging in vitro ( P < 0 .05 ) . The confocal laser scanning microscopy showed that nanoparticles mediated by tLyP-1 can targetedly aggregate to cell membrane of MDA-MB-231 and penetrate into the cell ,but not to HUVEC . The flow cytometry showed that intracellular fluorescence intensity of nanoparticles mediated by tLyP-1 in MDA-MB-231 group was higher than that in control groups ( P <0 .05) . The CCK8 assay indicated that different concentrations of nanoparticles had no significant effects on cell activity ( P > 0 .05 ) . Conclusions A novel ultrasound contrast agent , targeted phase-shift lipid nanoparticles mediated by tumor homing and penetrating peptide tLyP-1 ,is prepared successfully . It can target to MDA-MB-231 cell and penetrate into the cell in vitro ,and enhance ultrasound imaging in vitro after LIFU irradiation ,which expected to become a novel tumor targeted ultrasound contrast agent and achieve ultrasound molecular imaging at the level of tumor cell .

BACKGROUNDTo determine the long-term efficacy and persistence of Chinese infants after receiving only active plasma-derived hepatitis B vaccine, and to evaluate if providing booster vaccination after basic hepatitis B immunization is necessary.

METHODSInfants who were born in 1986-1988 in four demonstrative hepatitis B immunization trial areas of Hunan, Guangxi, Hebei and Shanghai after receiving only active plasma-derived hepatitis B vaccination, had been randomly followed up for 15 years. HBsAg,anti-HBs and anti-HBc in 21 680 person-times were tested using commercial SPRIA kits.

RESULTSPrevalence of HBV carriers was less than 1.66% among all children vaccinated with only active plasma-derived hepatitis B vaccine in 4 clinical trial areas. Prevalence of HBsAg did not increase with years after vaccination,90%(95% Cl:83.1%-97.2%) effectiveness of hepatitis B vaccine persisted for 15 years in preventing chronic HBV infection. Carriage, HBV infection and efficacy were not different among all age groups (P>0.05). Seroprotection rate (anti-HBs?10 mIU/ml) and quantity of anti-HBs were significantly decreased with years after vaccination. Seroprotection rates of anti-HBs were 40%-50% and 30%-42% during the 9th-10th year and the 13th-14th ear of vaccination, respectively. Titer of anti-HBs declined?by 90% after 14 years.

CONCLUSIONSThese results showed that long-term efficacy of only active plasma-derived hepatitis B vaccination, which was not affected by decline in seroprotection rate and titer of anti-HBs. For children and adults whose immune status is normal, booster doses of vaccine are not recommended.

Adolescent ; Child ; Child, Preschool ; Follow-Up Studies ; Hepatitis B ; prevention & control ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; immunology ; Humans ; Infant ; Infant, Newborn ; Vaccination

Osteoarthritis (OA) is the most common form of arthritis and the leading cause of old age disability, affecting an estimated 302 million people worldwide. OA is seriously overlooked in the world. The awareness of OA and the popularization of standardized diagnosis and treatment are all lacking. Knees, hips, and hands are the most commonly affected joints in OA. Based on the experience of diagnosis and treatment, consensus and guidelines, we formulated this diagnosis and treatment standard in order to standardize the diagnosis and treatment of OA. We hope that our standard can reduce misdiagnosis and mistreatment and improve the prognosis of OA.

Objective To evaluate the effectiveness and safety of moxibustion for knee osteoarthritis and the methodological quality of systematic reviews(SRs).Methods SRs of moxibustion for knee osteoarthritis were retrieved from CNKI,VIP,Wanfang Data,SinoMed,PubMed,Cochrane Library,Embase and Web of Science was conducted from the establishment of the databases to February 10,2022.AMSTAR 2 was used to assess the methodological quality of SRs.The randomized controlled trials(RCTs)included in these SRs were screened and summarized according to inclusion standard.RevMan 5.4 software was used for Meta-analysis,and GRADE approach was used to assess the certainty of evidence.Results A total of 15 SRs were included.The evaluation results of the AMSTAR 2 showed that the methodological quality was very low for 14 SRs,and low for other 1 SR.A total of 36 RCTs were included.Meta-analysis results showed that compared with the non-steroidal anti-inflammatory drugs(NSAIDs),the moxibustion group had better effects on improvement of WOMAC scores[mean difference(MD)=-5.95;95%confidence interval(CI):-9.25 to-2.65;low quality],relieving pain[MD=-1.26;95%CI:-2.19 to-0.32;very low quality],and improving effective rate[risk ratio(RR)=1.16;95%CI:1.11 to 1.22;low quality].In the moxibustion group,some patients experienced blisters,and most healed in 3 days.Conclusion Moxibustion has advantages in pain reduction and improving effective rate compared with routine Western therapy for knee osteoarthritis.However,well-designed high-quality RCTs are needed for further verification.

Objective:To explore the screening scheme of gastric cancer in large-scale natural population in Wuxi.Methods:From December 2016 to December 2019, 105 865 residents of 19 communities (villages) in six streets of Xinwu District, Wuxi were randomly enrolled in this study by random number table. A household epidemiological questionnaire survey was conducted among 50 063 target population subjects (aged 40-69), and then, respondents were divided into four categories, category Ⅰ: HP (-), PG (-); category Ⅱ: HP (+ ), PG (-); category Ⅲ: HP (+ ), PG (+ ); category Ⅳ: HP (-), PG (+ )according to the serological Helicobacter pylori ( HP) antibodies and pepsinogen (PG) test results. People in category Ⅲ and Ⅳ were all selected into group C and group D respectively, then individuals 3 times of group D were randomly selected from category Ⅰ to assign to group A, and individuals 3 times of group C from category Ⅱwere assigned to group B in the same way. Remaining individuals in category Ⅰ and Ⅱ who had first-degree family history of gastric cancer were also included in group A and group B, respectively. Endoscopic and pathological examination were performed on the above enrolled subjects for high grade intraepithelialneoplasia (HGIN), early gastric cancer and gastric cancer. Results:Of the 50 063 target subjects, 31 508 questionnaires were finally collected, with a participation rate of 62.9%. A total of 19 745 people were tested for serology, and the participation rate was 39.4% (19 745/50 063). Serological results showed that there were 11 152 people (56.48%) in category Ⅰ, 8 170 (41.38%) in category Ⅱ, 124 (0.63%) in category Ⅲ, and 299 (1.51%) in category Ⅳ. According to the exclusion criteria and principle of voluntariness, 3 400 individuals were candidates to undergo gastroscopy. Finally, a total of 2 389 people came to the hospital for gastroscopy, 1 263 in group A, 814 in group B, 86 in group C and 226 in group D, with an overall response rate of 70.3% (2 389/3 400), target population participation rate of 4.8% (389/50 063), and the overall population participation rate of 2.3% (2 389/105 865). In the 2 389 cases, there were 32 cases (1.34%) of HGIN and gastric cancer by gastroscopy and biopsy pathology, among which 1 case (3.125%) aged 40-49, 9 (28.125%) aged 50-59, and 22 (68.750%) aged 60-69. Among the 32 cases, 25 cases (78.13%)were pathologically confirmed as having HGIN or early gastric cancer by endoscopic submucosal dissection or surgical operation. By eliminating 810 people (including 3 gastric cancer) without first-degree family history with gastric cancer in group Ⅰ and Ⅱ, and increasing the gastroscopy screening age to 50 years (exluding 214 people aged 40-49, including 1 gastric cancer), the number of people who should undergo gastroscopy could be reduced from 2 389 to 1 365, and 28 cases of HGIN or gastric cancer were still detected, including 22 HGIN or early gastric cancer.Conclusion:Gastroscopy after the screening with epidemiological, serological tests, age and first-degree relative with gastric cancer family history is suitable for gastric cancer screening in Wuxi. Based on Chinese national conditions, a new community gastric cancer screening program is recommended in Wuxi considering cost-effectiveness, which includes those over 50 years old, serological PG (+ ) and first-degree relatives with family history of gastric cancer.

Objective:To investigate the effect of ultrasound monitoring of inferior vena cava collapse index (IVC-CI) guiding fluid replacement on circulation in elderly patients during induction of general anesthesia.Methods:A total of 71 elderly patients who underwent elective surgery under general anesthesia and tracheal intubation at Hunan Provincial People′s Hospital from April 2021 to September 2022 were randomly divided into control group (35 cases) and observation group (36 cases) using a random number table method. Before anesthesia, both groups of patients underwent IVC ultrasound examination and calculated the IVC-CI value. For patients with IVC-CI≥40%, the observation group was given 8 ml/kg of crystal solution before anesthesia induction, while the control group was not treated. The incidence of hypotension, the use of vasoactive drugs, and the total infusion volume from anesthesia induction to skin incision were recorded in two groups. Mean arterial blood pressure (MBP), heart rate (HR), oxygen saturation (SpO 2), cardiac index (CI), and cardiac volume variability (SVV) before anesthesia (T 0), 5 min after induction (T 1), 1 min after tracheal intubation (T 2), 5 min after tracheal intubation (T 3), 10 min after tracheal intubation (T 4), and 1 min before skin incision (T 5) were recorded and compared between the two groups. Results:The incidence of hypotension (27.8% vs 60.0%) and utilization rate of vasoactive drugs (25.0% vs 48.6%) in the observation group were lower than those in the control group, and the total infusion volume during anesthesia induction was higher than that in the control group, with statistical significance (all P<0.05). SVV, CI and MBP at T 1, T 3, T 4 and T 5 were significantly different from those at T 0 in the control group ( F=3.85, 14.66, 3.96, all P<0.05). SVV, CI and MBP at T 1, T 3, T 4 and T 5 in the observation group were significantly different from those at T 0 ( F=3.51, 13.20, 4.35, all P<0.05). There was no significant difference in SVV, CI, MBP, HR and SpO 2 between 2 groups (all P>0.05). Conclusions:For the elderly patients with preoperative IVC-CI≥40%, pre-filling with 8ml/kg crystal solution before anesthesia induction can significantly reduce the incidence of hypotension and the utilization rate of vasoactive drugs in the elderly patients during anesthesia induction.

Objective:To explore the clinical phenotype and genetic etiology for seven children with CHARGE syndrome (CS).Methods:Clinical data of 7 children with CS diagnosed between March 2020 and December 2022 at the Children′s Hospital Affiliated to Zhengzhou University were analyzed. Genomic DNA was extracted from peripheral blood samples from the children and their parents, and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliatedto Zhengzhou University (Ethics No. 2024-K-023).Results:The ages of the children had ranged from 1 day after birth to 12 years old, and all of them had shown growth retardation. The reasons for their admission had included postnatal breathing, swallowing and feeding difficulties in five cases. One child was found to have abnormal external genitalia in conjunct with hearing impairment, whilst another child had shown no secondary sexual characteristics during puberty. All of the children were found to harbor CHD7 gene variants, which included 3 nonsense variants, 2 frameshifting variants and 2 missense variants, i. e., c. 6292C>T (p.R2098*), c.2754G>A (p.W918*), c. 469C>T (p.R157*), c. 3308T>A (p.V1103D), c. 7111delC (p.Q2371Kfs), c. 6023delA (p.D2008Vfs) and c. 3565C>T (p.R1189C). All of the variants were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 3308T>A (p.V1103D) and c. 3565C>T (p.R1189C) variants were rated as likely pathogenic (PS2+ PM2_Supporting+ PP3), whilst the remainders were rated as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:There is strong clinical and genetic heterogeneity in CS. Early genetic testing may facilitate accurate diagnosis. The detection of novel variants has expanded the phenotypic spectrum of CS and the mutational spectrum of the CHD7 gene.