Objective To explore the expression and clinical significance of autophagy related proteins Beclin-1,microtubule-associated protein 1 light chain 3(LC3)in placenta tissues of pregnant women with fetal growth restric-tion(FGR).Methods A total of 40 pregnant women undergoing delivery due to FGR and 40 pregnant women un-dergoing normal delivery in the Second Affiliated Hospital of Zhengzhou University were enrolled as FGR group and healthy group between August 2022 and August 2023.The general clinical data in the two groups were collected.The levels of Beclin-1 and LC3 mRNA in placenta tissues were detected by PCR,and expressions of Beclin-1 and LC3 proteins were detected by immunohistochemistry.The differences in positive of Beclin-1 and LC3 proteins among patients with different clinical data were analyzed.Results The placental thickness,placental mass and neonatal weight in FGR group were lower than those in healthy group(P＜0.05).The mRNA levels of Beclin-1 and LC3 in FGR group were higher than those in healthy group(P＜0.05)and positive expression rates of Beclin-1 and LC3 proteins were significantly higher than those in healthy group(P＜0.05).There was significant difference in positive expression profile of Beclin-1 and LC3 proteins among patients with different placental thickness,placental mass and neonatal weight(P＜0.05).Conclusions The positive expressions of autophagy genes(Beclin-1 and LC3)are related to FGR,and their specific expression levels are closely related to fetal growth and development.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:To systematically assess the risk factors for acute pancreatitis in pregnancy (APIP) in China in recent 10 years.Methods:Acute pancreatitis, pregnancy, risk factors and clinical features were used as search terms. Case-control studies on APIP in China were retrieved by computer from PubMed, Cochrane Library, Embase, CNKI, Wanfang, VIP and Chinese Biomedical Literature Database from December 2011 to December 2021. RevMan 5.4 software was utilized for Meta analysis.Results:A total of 1525 APIP patients (645 severe cases and 880 mild cases) were included in 26 literatures. Meta analysis showed that early pregnancy, late pregnancy, hyperlipidemia and biliary etiology were the risk factors for APIP. In the early pregnancy, 4.22% of patients were in the severe group and 10.43% were in the mild group; In the late pregnancy, 81.95% of the patients were in the severe group and 69.72% were in the mild group. The causes of hyperlipidemia accounted for 52.16% in the severe group and 22.69% in the mild group. The causes of biliary disease accounted for 27.96% in the severe group and 41.71% in the mild group. All the differences of the above indicators between groups were statistically significant (all P value <0.05). The age at onset, body mass index, serum C-reactive protein and triacylglycerol levels of severe patients were higher than those of mild patients, and were positively correlated with the severity of APIP ( MD values were 0.99, 65.97, 1.33, 6.44, 95% CI values were 0.03-1.96, 0.59-2.08, 23.43-108.50, 4.49-8.39, P values were 0.04, 0.0005, 0.002, <0.001). The levels of blood calcium and serum albumin were lower than those of mild patients, and were negatively correlated with the severity of APIP ( MD values were -0.37, -5.93, 95% CI values were -0.50--0.24, -9.11--2.75, P values were <0.001, 0.003). Conclusions:Acute pancreatitis can occur in all stages of pregnancy. Early pregnancy is mainly mild, and severe cases are more common in late pregnancy. Hypertriglyceridemic pancreatitis progresses rapidly, and tends to become more severe in China.

Objective:To explore the risk factors of urinary incontinence (UI) in China by using random forest algorithm, and to evaluate the predictive effect of each risk factor on UI.Methods:A baseline survey with a multistage stratified cluster sampling design was conducted between February 2014 and January 2016, and followed up by telephone from June to December 2018. A total of 55 477 adult women from six provinces of China participated the survey. According to the ratio of 1:1, under sampling method was used to randomly select the same number of women as UI from the non UI women. The data were randomly divided into training set and verification set according to 7:3. The training set was used to establish the random forest model, which including the candidate variables with P<0.2 in univariate analysis, and the verification set was used to verify the predictive effects. Results:A total of 30 658 patients (55.26%, 30 658/55 477) completed the follow-up, the median follow-up time was 3.7 years. Among the 24 985 women without UI at baseline, 1 757 (7.03%, 1 757/24 985) had UI at followed up, including 1 117 (4.47%, 1 117/24 985) with stress UI, 243 (0.97%, 243/24 985) with urgency UI and 397 (1.59%, 397/24 985) with mixed UI. When fixed the number of features as 2 and the number of random trees as 300 in the random forest model, the out of bag error rate estimation was the lowest; with such parameter settings, the classification accuracy was 64.3%, the sensitivity was 64.2%, and the specificity was 64.4%. The top10 predictive UI factors that screening by the variable importance measure in random forest model were obtained as follows: age, parity, delivery pattern, body mass index (BMI), menopause, history of diabetes, education level, history of pelvic surgery, regions, and marital status.Conclusion:We identified the top10 predictive UI factors that screening by the variable importance in random forest model as follows: age, parity, delivery pattern, BMI, menopause, history of diabetes, education level, history of pelvic surgery, regions, and marital status.

Objective:To evaluate the feasibility and clinical results of micro-dissected chimeric (II-MCh) perforator flap based on the descending branch of lateral circumflex femoral artery(d-LCFA) for repairing composite soft tissue defects of limbs.Methods:From April, 2011 to December, 2019, a total of 19 cases of composite soft tissue defects of limbs combined with deep cavity were repaired with II-MCh perforator flap or micro-dissected thin lobulated (III-MPCh) perforator flap based on d-LCFA. The flap was micro-dissected before cut off the perforator. The deep dead cavity was filled with muscle flap, and the superficial wound was repaired with micro-dissected thin perforator flap. The sizes of flaps were 6.0 cm×3.0 cm-33.0 cm×8.0 cm. The muscle flaps were cut with volumes of 5.0 cm×3.0 cm×1.0 cm-13.0 cm×10.0 cm×1.5 cm. Donor sites of the flap were closed directly. Postoperative reviews were assigned at 1, 3, 6, 9 and 12 months. The appearance, colour, texture and recurrence of infection of the flap were checked and recorded.Results:Sixteen flaps survived successfully without necrosis and with primary healing at the donor sites. Two flaps had venous occlusion within 24 hours after surgery and healed after surgical exploration and venous anastomosis. One flap had arterial crisis within 24 hours after surgery and healed after surgical exploration and arterial anastomosis. All patients entered follow-up for 8-36 months with an average of 16 months. All recipient sites achieved satisfactory appearance and function, and only linear scars left at the donor sites.Conclusion:The II-MCh perforator flap based on d-LCFA is a special modality of anterolateral thigh perforator flap, which achieves a satisfying appearance at the recipient site by micro-dissecting the flap within one procedure. This emerging technique can effectively fill the dead cavity, and is an effective method to repair complex soft tissue defects of limbs combined with deep cavity.

The COVID-19 outbreak may have some impact on the use of biologics in psoriatic patients because immunosuppressive effects of biologics may potentially alter the susceptibility of patients to the virus, deteriorate the condition of infected patients or even change the prognosis of infection. According to currently available recommendations from international psoriasis academic organizations and specialists, as well as specific situation in China, the authors provide some guidance on the use of biologics for psoriatic patients undergoing or planning to undergo treatment with biologics, those with low or high risk of infection, and for those with or without COVID-19 infection, so as to provide references for clinical practice.

Objective To evaluate the effect of sildenafil on the expression of hexokinase-2 (HK-2) in lung tissues in a rat model of pulmonary arterial hypertension. Methods Thirty-two male Sprague-Dawley rats, aged 2 months, weighing 200-220 g, were allocated into 4 groups with 8 rats in each group using a random number table: control group ( group C), pulmonary arterial hypertension group ( group PAH), low-dose sildenafil group (group S1 ) and high-dose sildenafil group (group S2 ). The model of pul-monary arterial hypertension was established through combining left pneumonectomy with subcutaneous in-jection of 60 mg∕kg monocrotaline. Two percent sildenafil 30 and 50 mg∕kg were administered by intragastric gavage once a day for 3 consecutive weeks starting from 5 weeks after pneumonectomy in S1 and S2 groups, respectively. The chest was opened after the end of administration for measurement of mean pulmonary arte-rial pressure (mPAP) and right ventricular systolic pressure (RVSP). The hearts and lungs were excised for determination of the percentage of the thickness of tunica media of pulmonary arterioles, size of right ventricular cardiomyocytes, α-smooth muscle actin (α-SMA) expression (by immunohistochemistry) and expression of hypoxia-inducible factor-1α (HIF-1α) and HK-2 ( by Western blot). Results Compared with group C, the mPAP, RVSP and percentage of MT were significantly increased, the size of right ven-tricular cardiomyocytes was enlarged, and the expression of HIF-1α, HK-2 and α-SMA was up-regulated in PAH and S1 groups, and the RVSP and percentage of MT were significantly increased, the size of right ventricular cardiomyocytes was enlarged, and the expression of HIF-1α, HK-2 and α-SMA was up-regula-ted (P<0. 05), and no significant change was found in mPAP in group S2 (P>0. 05). Compared with group PAH, the percentage of MT was significantly decreased, the size of right ventricular cardiomyocytes was decreased, and the expression of HIF-1α, HK-2 and α-SMA was down-regulated in group S1 , and the mPAP, RVSP and percentage of MT were significantly decreased, the size of right ventricular cardiomyo-cytes was decreased, and the expression of HIF-1α, HK-2 and α-SMA was down-regulated in group S2 (P<0. 05). Conclusion The mechanism by which sildenafil inhibits proliferation of pulmonary vascular smooth muscle cells is related to inhibiting the expression of HK-2 in lung tissues in a rat model of pulmona-ry arterial hypertension.

Objective: To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on leukemic cell line U937 cells with NPM1 mutation. Methods: Human acute myeloid leukemia cell line U937 was explored, NPM1 mutated (A type) plasmids were transfected into U937 to form stable clones A1 and A2, which were identified by Western blot and Co-immunoprecipitation. The cell proliferation was measured by methylthiazolyl tetrazolium bromide (MTT) ; cell cycle and cell apoptosis were explored by flow cytometric; cell colony formation was measured by microscope count, the molecular pathways related to cell proliferation were measured by Western blot. Results: ①The cell proliferations of mutant A1 and A2 were inhibited significantly by 52.6% and 35.8% (P<0.05) , respectively under ATRA exposure. ②The percentages of G₀/G₁ stage of mutant A1 and A2 increased by 20.1% and 35.8%, respectively under ATRA exposure. ③All the U937 leukemic cells were inhibited under ATRA exposure; the decreased percentages of vector, wild-type and mutant NPM1 cells were 32.7%, 57.9% and 90.9% respectively. ④p-ERK decreased obviously after ATRA exposure in NPM1 mutated leukemic cells. ⑤More mutant NPM1 cells inclined to apoptosis under the exposure of ATRA and cytotoxic drugs than cytotoxic drugs alone, meanwhile more cells apoptosis occurred when ATRA was administrated after cytotoxic drugs exposure. Conclusions ATRA could inhibit cell proliferation and colony formation, blocked the cell cycle in the G₀/G₁ stage accompanied by the significant reduction of p-ERK in U937 leukemic cells with NPM1 mutation. Besides, ATRA could synergize with drugs to suppress the leukemic cells survival more effectively when ATRA was administered after the cytotoxic drugs exposure in U937 leukemic cells with NPM1 mutation.

This study was aimed to reveal the species characteristics of Chinese patent medicines for antitussive ef-fect and provide references for developing new drugs. This research targeted Chinese patent medicines for antitussive effect which were included in the Pharmacopoeia of the People's Republic of China and the New National Chinese Patent Medicines as well as those characterized by keywords such as cough cure, cough alleviating, antitussive effect, cough, persistent cough. The analysis was made on the species characteristics, such as the number of Chinese patent medicines for antitussive effect, license number, ethnomedicine patent medicines, drugs for children use, protection of varieties of traditional Chinese medicine, the number of drugs, the generic names of drug, and drug forms. The results showed that 684 Chinese patent medicines for antitussive effect collected in this research had ac-counted for 8.60% of the total 7 260 of Chinese patent medicines. A total of 7 450 license numbers were approved, and 33% of the Chinese patent medicines shares one license number. One Chinese patent medicine owns 16.6 li-cense numbers on average. Ethnomedicine patent medicines had 3 Tibetan prescriptions such as the Shiwuwei Chenxiang pill and 4 Mongolian prescriptions, such as the Siwei Tumuxiang powder. Drugs for children accounted for 14%, including 9 forms. The type of the generic names of drug reached 16 and most of them originate from abbrevia-tions of the main drug in prescription. The number of drugs in prescription ranges from 8 to 16. Chinese patent medicines for antitussive effect involved 16 forms, of which the proportion of the use of solid preparation was higher than the liquid preparation. It was concluded that Chinese patent medicines for antitussive effect were characterized by such advantages such as a variety of species, various forms, the reasonable number of drugs, considerable medicine retail market share and drug for children use which can meet the clinical needs, and meanwhile some prob-lems, such as a lack of criteria for the generic names of drug, the homogenization of fierce competition, and inade-quacy of ethnomedicine patent medicines.