Adherence to the EAT-Lancet diet reduces the risk of head and neck cancers in 101,755 American adults: a prospective cohort study.

OBJECTIVES: The aim of this study was to explore the relationship between the EAT-Lancet diet (ELD) and head and neck cancers (HNCs) in 101,755 Americans enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. STUDY DESIGN: Prospective cohort study. METHODS: ELD score was calculated to assess participant's adherence to ELD. Cox hazard regression models were utilised to evaluate the association of ELD and dietary components with HNC risk. Restricted cubic spline (RCS) plots were employed to explore the linearity of the relationships. Predefined subgroup analyses and sensitivity analyses were performed to identify potential effect modifiers and to assess the stability of the findings, respectively. RESULTS: After a mean follow-up of 8.84 years, 279 cases of HNCs, including 169 cases of oral cavity and pharyngeal cancers and 110 cases of laryngeal cancer were recorded. This study observed a dose-response negative correlation between ELD and HNCs (hazard ratio [HR]Q4 vs Q1: 0.52; 95% confidence interval [CI]: 0.34, 0.80; P-trend = 0.003; HRper SD increment: 0.80; 95% CI: 0.71, 0.91), and oral cavity and pharyngeal cancers (HRQ4 vs Q1: 0.52; 95% CI: 0.31, 0.88; P-trend = 0.008; HRper SD increment: 0.78; 95% CI: 0.66, 0.92). Analysis using RCS plots indicated a significant linear association between adherence to the ELD and reduced risk of HNCs and oral cavity and pharyngeal cancers (P-nonlinearity > 0.05). Subgroup analysis did not reveal significant interaction factors (P-interaction > 0.05), and sensitivity analysis confirmed the robustness of this study. Additionally, negative correlations were found between the consumption of fruits and whole grains and HNCs (fruits: HRQ4 vs Q1: 0.58; 95% CI: 0.40, 0.84; P-trend = 0.010; whole grains: HRQ4 vs Q1: 0.51; 95% CI: 0.26, 0.97; P-trend = 0.004). CONCLUSION: Adherence to ELD contributes to the prevention of HNCs.

Association between non-alcoholic fatty liver disease and metabolic abnormalities in children with different weight statuses.

OBJECTIVES: Both obesity and non-alcoholic fatty liver disease (NAFLD) increase the risk of metabolic abnormalities. However, the metabolic status of children suffering from NAFLD and exhibiting various subtypes of obesity is currently unclear. We aimed to explore the association between NAFLD and metabolic abnormalities in children with different weight statuses. METHODS: We included 6086 participants aged 6-18 years from the China Child and Adolescent NAFLD Study (CCANS), all of whom had undergone ultrasonography or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to identify NAFLD and metabolic abnormalities, including hyperglycemia, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol, high total cholesterol, and hyperuricemia. RESULTS: Among the participants, there were 2408 children with obesity and NAFLD, 174 with NAFLD, 2396 with obesity, and 1108 without obesity and NAFLD. The odds ratios (ORs) of suffering from individual metabolic abnormalities were significantly greater in children with obesity and NAFLD than in children without obesity and NAFLD, with ORs ranging from 6.23 (95% CI: 4.56, 8.53) to 1.77 (95% CI: 1.06, 2.94). The ORs of metabolic abnormalities, except for low HDL-C, were greater in children with NAFLD alone than in children without obesity or NAFLD, with ORs ranging from 4.36 (95% CI: 2.77, 6.84) to 2.08 (95% CI: 1.14, 3.78). Notably, obesity and NAFLD had a multiplicative effect on overall metabolic abnormalities, high TG levels, and low HDL-C levels. CONCLUSIONS: Children with obesity and NAFLD could be at a significantly increased risk of metabolic abnormalities. Even for children without obesity, NAFLD appears to be associated with an increased risk of experiencing a worsened metabolic status.

[Questionnaire survey of the application of four objective indicators necessary for standardized diagnosis of Sjögren's syndrome].

Objective: To investigate the current status and challenges of carrying out the four objective indicators which are necessary for the Sjögren's syndrome (SS) diagnosis in hospitals all over China. Methods: A questionnaire survey was conducted online by Questionstar from May to July 2023 among rheumatologists nationwide, to investigate whether unstimulated salivary flow (UWSF), Van Bijsterveld score (VBS), Schirmer test and labial gland focus score (FS) are carried out in their hospitals and the challenges that hinder their development. A cohort of patients with established SS was enrolled to verify the importance of the four objective indicators in diagnosing SS. Statistical analyses were performed using the chi-square test. Results: The questionnaire was completed by rheumatologists from 660 hospitals in 225 cities of 32 provinces, autonomous regions and municipalities all over China (one doctor from each hospital completed the questionnaire), of which 548 (83.0%) were tertiary care hospitals. The rate of carrying out the objective indicators in 660 hospitals was low: UWSF (290/660, 43.9%), FS (497/660, 75.3%) and VBS (393/660, 59.5%). The percentage of hospitals who consider it difficult to carry out UWSF, VBS, minor labial gland biopsy and Schirmer test was 92.6%(611/660), 69.4%(458/660), 59.8%(395/660) and 58.6%(387/660), respectively. All four objective indicators mentioned above could be carried out in only 139 (21.1%) hospitals. In 521 hospitals in which less than four objective indicators could be carried out, 23.2% (121/521) of rheumatologists selected clinical experience to diagnose SS. A total of 180 patients with SS diagnosed by perfecting all objective indices and meeting the 2016 the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria were included, 173 females (96%), aged (46.6±13.6) years, with the missed diagnosis rate was 17.8% (32/180) assuming their labial FS was unavailable. In 166 patients with established SS who met the classic 2002 AECG criteria, 160 females (96%), aged (47.0±13.6) years, the missed diagnosis rate was 52.4% (87/166) assuming their labial FS was unavailable; or 10.8% (18/166) assuming their UWSF was unavailable. SS diagnosis couldn't be estimated according to 2002 AECG criteria, assuming both labial FS and UWSF were unavailable in 156 (94.0%) patients with positive anti-SSA/Ro; or assuming either labial FS or UWSF was unavailable in 10 (6.0%) patients with negative anti-SSA/Ro. Conclusion: The application rates of four objective indicators necessary for SS diagnosis are low, the rate of carrying out labial gland biopsy should be increased, and the labial FS reports and UWSF test should be standardized.

[Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma].

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.

[Inhibitory effect of small-molecule compound AM679 targeting elongation-factor binding protein 2 on hepatitis B virus in vitro].

Objective: To explore the antiviral activity of the small-molecule compound AM679 in hepatitis B virus (HBV) replication and infection cell models. Methods: The positive regulatory effect of AM679 on EFTUD2 expression was validated by qPCR and Western blotting. HepAD38 and HepG2-NTCP cells were treated with AM679 (0.5, 1, and 2 nmol/L). Negative control, positive control, and AM679 combined with the entecavir group were set up. HBV DNA intra-and extracellularly, as well as the expression levels of intracellular HBV total RNAs and 3.5kb-RNA changes, were detected with qPCR. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels were measured in the cell supernatant by an enzyme-linked immunosorbent assay (ELISA). The t-test method was used for the statistical analysis of the mean difference between groups. Results: EFTUD2 mRNA and protein expression levels were significantly increased in HepAD38 and HepG2-NTCP cells following AM679 treatment, with a statistically significant difference (P < 0.001). Intra-and extracellular indicators such as HBV DNA, HBV RNAs, HBV 3.5kb-RNA, HBsAg, and HBeAg were decreased to varying degrees in both cell models, and the decrease in these indicators was more pronounced with the increase in AM679 concentration and prolonged treatment duration, while the combined use of AM679 and entecavir had a more significant antiviral effect. The HBV DNA inhibition rates in the supernatant of HepAD38 cells with the use of 2 nmol/L AM679 were 21% and 48% on days three and nine, respectively. The AM679 combined with the ETV treatment group had the most significant inhibitory effect (62%), with a P < 0.01. More active HBV replication was observed after silencing EFTUD2, while the antiviral activity of AM679 was significantly weakened. Conclusion: AM679 exerts anti-HBV activity in vitro by targeting the regulation of EFTUD2 expression.

[Analysis of clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues].

Objective: To explore the clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues. Methods: A retrospective analysis was performed according to different data types. An independent sample t-test, Mann-Whitney U test, chi-square test, or Fisher's exact probability method were used. Chronic hepatitis B patients followed up for four years were collected from the follow-up case database of the Department of Infectious Diseases of Zhongshan Third Hospital from January 2009 to December 2018 and were divided into two groups, A and B, with 87 and 145 cases respectively, according to the duration of HBeAg-negativity≤ 3 and persistent positivity >3 years. Statistical analysis was conducted on the age, gender, family history, baseline, follow-up visit duration, liver function, and other data among the two patient groups. Results: There were no statistically significant differences in gender, age, family history of liver cirrhosis, family history of liver cancer, liver cirrhosis condition before treatment, fatty liver disease combined condition before treatment, baseline HBsAg, anti-HBc, alanine aminotransferase, albumin, or total bilirubin between the two groups of patients (P > 0.05). HBV DNA and HBeAg were significantly higher in group B than those in group A at baseline, with P≤0.001. Aspartate aminotransferase and γ-glutamyl transferase were significantly higher in group A than those in group B at baseline. The proportion of family history of hepatitis B was significantly higher in group B (69.0%) than that in group A (50.6%) among the two groups of patients, and the difference was statistically significant (P = 0.005). The proportion of mothers with hepatitis B was significantly higher in group B (25.5%) than in group A (11.5%), P = 0.010. During the treatment process, the HBV DNA quantification was significantly higher in group B than that in group A at 0.5 and 1 years (P≤0.002). The proportion of HBV DNA <100IU/ml was also significantly different at six months and one year (χ(2)=30.327, P < 0.001 and χ(2)=11.779, P = 0.001). The HBsAg level was higher in group B than that of group A in the second and fourth years, P < 0.05. During the entire treatment process, the HBeAg level was significantly higher in group B than that in group A (P < 0.001). A total of seven cases developed liver cirrhosis or cancer during follow-up, including three cases in group A and four cases in group B (P > 0.05). Conclusion: HBeAg-positive patients with chronic hepatitis B have persistent HBeAg positivity when treated with long-term nucleos(t)ide analogues. Accordingly, a greater proportion of this kind of patient family and mothers have a remarkable history of hepatitis B and a reduced HBV DNA relapse rate in the early stages (within a year or less).

Significance of the plasma membrane H+-ATPase and V-ATPase for growth and pathogenicity in pathogenic fungi.

Pathogenic fungi are widespread and cause a variety of diseases in human beings and other organisms. At present, limited classes of antifungal agents are available to treat invasive fungal diseases. With the wide use of the commercial antifungal agents, drug resistance of pathogenic fungi are continuously increasing. Therefore, exploring effective antifungal agents with novel drug targets is urgently needed to cope with the challenges that the antifungal area faces. pH homeostasis is vital for multiple cellular processes, revealing the potential for defining novel drug targets. Fungi have evolved a number of strategies to maintain a stable pH internal environment in response to rapid metabolism and a dramatically changing extracellular environment. Among them, plasma membrane H+-ATPase (PMA) and vacuolar H+-ATPase (V-ATPase) play a central role in the regulation of pH homeostasis system. In this chapter, we will summarize the current knowledge about pH homeostasis and its regulation mechanisms in pathogenic fungi, especially for the recent advances in PMA and V-ATPase, which would help in revealing the regulating mechanism of pH on cell growth and pathogenicity, and further designing effective drugs and identify new targets for combating fungal diseases.

Assessment of healthcare quality among village clinicians in rural China: the role of internal work motivation.

INTRODUCTION: The quality of primary care is important for health outcomes among residents in China. There is evidence that internal work motivation improves the quality of healthcare provided by clinicians. However, few empirical studies have examined the relationship between internal work motivation and clinical performance among village clinicians in rural China. This study was performed to evaluate healthcare quality among village clinicians, then explore its relationships with internal work motivation among those clinicians. METHODS: We collected survey data using a standardised patient method and a structured questionnaire. We observed 225 interactions between standardised patients and village clinicians from 21 counties in three provinces. We used logistic regression models to analyse the relationships between work motivation and healthcare quality, then conducted heterogeneity analysis. RESULTS: Healthcare quality among village clinicians was generally low. There was a significantly positive correlation between internal work motivation and healthcare quality among village clinicians (P<0.1). Additionally, the positive effect of internal work motivation on healthcare quality was strongest among clinicians who received financial incentives and had a lighter workload (fewer patients per month) [P<0.1]. CONCLUSION: Healthcare quality among village clinicians requires urgent improvement. We recommend implementing financial incentives to stimulate internal work motivation among village clinicians, thus improving their clinical performance.

Stent pretreatment for internal carotid artery exposed to necrotic lesions in nasopharyngeal carcinoma.

BACKGROUND: Post radiation nasopharyngeal necrosis (PRNN) invading the internal carotid artery (ICA) contributes to the death of 69.2-72.7% of PRNN patients. ICA occlusion is an effective treatment to avoid fatal bleeding, while some patients are intolerant. We present a novel method that allows for these patients without interrupting blood flow through the ICA. METHODOLOGY: This study enrolled patients with PRNN-invaded ICA who were not suitable for ICA occlusion from April 2020 to November 2022. ICA stent pretreatment was performed in the 36 patients and followed the endoscopic nasopharyngectomy (ENPG) or conservative treatment for PRNN. We report the survival outcome and incidence of complications after stent implantation and compare the survival outcomes of ENPG and conservative treatment for PRNN followed by stent implantation. RESULTS: ICA stent pretreatment was performed in the 36 enrolled patients, among which 14 underwent ENPG, and 22 received conservative treatment. 27.8% patients died after a median follow-up of 15 months. The Kaplan-Meier estimates of overall survival were higher in the ENPG group than in the conservative treatment group. Karnofsky performance status (KPS) was significantly higher in the ENPG group than in the non-ENPG group. CONCLUSIONS: The innovative application of ICA stents is a promising treatment to improve outcomes in patients with PRNN invading the ICA who are unsuitable for ICA embolization, especially when followed by endoscopic surgery. However, methods to avoid postoperative cerebral ischemia and nasopharyngeal hemorrhage still require further study.

[Efficacy of high-dose dual therapy for Helicobacter pylori infection eradication in servicemen: a randomized controlled trial].

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.

[Clinical and laboratory features of SF3B1-mutated myeloproliferative neoplasms].

Objective: To explore the clinical and laboratory characteristics of SF3B1 gene mutations in myeloproliferative neoplasms (MPN) patients. Methods: The clinical data of 273 MPN patients who were diagnosed MPN and treated in the Second Hospital of Tianjin Medical University from November 2017 to March 2023 were retrospectively analyzed. There were 133 males and 140 females, with a median age M(Q1,Q3)of 56(46, 67) years. The molecular biology and cytogenetic characteristics were detected by second-generation sequencing (NGS) and R+G banding techniques, and the clinical and laboratory characteristics of patients with SF3B1 gene mutation were analyzed. Results: SF3B1 gene mutations were found in 13 patients (4.8%, 13/273).The types of SF3B1 mutations included missense (92.3%, 12/13) and nonsense mutations (7.7%, 1/13).Compared to the non-mutant cohort, patients in SF3B1 mutant cohort had older ages [68(51, 76) vs 56(45, 66)years,P=0.025], higher proportion of splenomegaly [46.2%(6/13) vs 15.8%(41/259),P=0.014]and secondary tumor [23.1%(3/13)vs 3.8%(10/260), P=0.018]with higher proportion of bone marrow blast [0.5%(0, 1.5%) vs 0(0, 0.5%),P=0.002] and lower hemoglobin[(104±36) vs (137±40) g/L,P=0.004] and hematocrit [31%(22%, 40%) vs 41%(35%, 52%),P=0.003]. All of the 10 patients in the SF3B1 mutant cohort whose ring sideroblast (RS) could be evaluated showed no RS formation. The overall survival, thrombosis-free survival and leukemia free survival of MPN patients in SF3B1 mutant cohort were 4.0 (2.0, 6.0), 2.0 (0.5, 4.5) and 4.0 (2.0, 6.0) years, respectively, while patients in the non-mutant cohort were 6.0 (3.0, 10.0), 5.0 (1.0, 8.0), 6.0 (3.0, 10.0) years, respectively, there were no statistical significance between two groups (Z=3.69, 1.66, 2.05, all P>0.05).The secondary tumor free survival of SF3B1 mutant cohort patients was 4.0 (2.0, 6.0) years, which was lower than that of non-mutant cohort patients [5.5 (3.0, 10.0) years, Z=18.18, P<0.001). Conclusions: MPN patients with SF3B1 gene mutations are older, more prone to splenomegaly and secondary tumors. They also have a higher proportion of bone marrow blast, lower hemoglobin and hematocrit, and show no RS formation.

[Clinical features and related factors of invasive pulmonary aspergillosis in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To study the clinical features and related factors of invasive pulmonary aspergillosis (IPA) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: This retrospective study enrolled patients hospitalized for AECOPD in ten tertiary hospitals of China from September 2017 to July 2021. AECOPD patients with IPA were included as case group, AECOPD patients without IPA were randomly selected as control group from the same hospitals and same hospitalization period as the patients with IPA using the random function in the software of Microsoft Excel 2003, at a ratio of 2∶1. The clinical characteristics, treatment and outcome were compared between the two groups. Binary logistic regression model was used to analyze the factors associated with IPA in AECOPD patients. Results: A total of 14 007 inpatients with AECOPD were included in this study, and 300 patients were confirmed to have IPA, with an incidence rate of 2.14%. According to the above matching method, 600 AECOPD patients without aspergillus infection were enrolled as the control group. The age of the case group and the control group were (72.5±9.7) and (73.5±10.3) years old, with 78.0%(n=234) male and 76.8%(n=461) male, respectively. There were no significant differences in age and gender composition between the two groups (all P>0.05). The prognosis of case group was significantly worse than that of the control group, with longer hospital stay [M(Q1,Q3)], [14 (10-20) d vs 11 (8-15) d, P<0.001], higher ICU admission rate [16.3% (49 case) vs 10.0% (60 case), P=0.006], higher in-hospital mortality [4.0% (12 cases) vs 1.3% (8 cases), P=0.011], and higher hospitalization costs (28 000 ¥ vs 13 700 ¥, P<0.001). The smoking index of the case group and proportions of patients with diabetes mellitus, chronic pulmonary heart disease in the case group were significantly higher than those in control group (all P<0.05). In terms of clinical features, the proportions of patients with cough, expectoration, purulent sputum, hemoptysis and fever in the case group were higher than those in the control group, the serum albumin was significantly lower than that in the control group, and the proportions of patients with bronchiectasis and pulmonary bullae on imaging were significantly higher than those in the control group (all P<0.05). Diabetes (OR=1.559, 95%CI: 1.084-2.243), chronic pulmonary heart disease (OR=1.476, 95%CI: 1.075-2.028), bronchiectasis (OR=1.506, 95%CI: 1.092-2.078), pulmonary bullae (OR=1.988, 95%CI: 1.475-2.678) and serum albumin<35 g/L (OR=1.786, 95%CI: 1.325-2.406) were the related factors of IPA in patients with AECOPD. Conclusions: The incidence of IPA in AECOPD patients is relatively high and the prognosis of these patients is worse. Diabetes, chronic pulmonary heart disease, bronchiectasis, pulmonary bulla, hypoproteinemia are the related factors of IPA in patients with AECOPD.

[Effects of ppk1 deletion on the drug susceptibility of uropathogenic Escherichia coli producing ESBLs].

To investigate the effect and the mechanism of ppk1 gene deletion on the drug susceptibility of uropathogenic Escherichia coli producing extended-spectrum beta-lactamases (ESBLs-UPEC). The study was an experimental study. From March to April 2021, a strain of ESBLs-UPEC (genotype was TEM combined with CTX-M-14) named as UE210113, was isolated from urine sample of the patient with urinary tract infection in the Laboratory Department of Guangzhou Eighth People's Hospital, meanwhile its ppk1 gene knock-out strain Δpk1 and complemented strain Δpk1-C were constructed by suicide plasmid homologous recombination technique, which was used to study the effect of ppk1 gene on ESBLs-UPEC drug sensitivity and its mechanism. The drug susceptibility of UE210113, Δpk1, and Δpk1-C were measured by Vitek2 Compact System and broth microdilution method. The quantitative expression of ESBLs, outer membrane protein and multidrug efflux systems encoding genes of UE210113, Δpk1 and Δpk1-C were performed by using qRT-PCR analysis. By using two independent sample Mann-Whitney U test, the drug susceptibility results showed that, compared with UE210113 strain, the sensitivities of Δpk1 to ceftazidime, cefepime, tobramycin, minocycline and cotrimoxazole were enhanced (Z=-2.121,P<0.05;Z=-2.236,P<0.05;Z=-2.236,P<0.05;Z=-2.121,P<0.05), and the drug susceptibility of Δpk1-C restored to the same as which of UE210113 (Z=0,P>0.05). The expression levels of ESBLs-enconding genes blaTEM and blaCTX-M-14 in Δpk1 were significantly down-regulated compared with UE210113, but the expression was not restored in Δpk1-C. The expression of outer membrane protein gene omp F in Δpk1 was significantly up-regulated, while the expression of omp A and omp C were down-regulated. The results showed that the expression of multidrug efflux systems encoding genes tol C, mdt A and mdtG were down-regulated in Δpk1 compared with UE210113. The expression of all of the outer membrane protein genes and the multidrug efflux systems genes were restored in Δpk1-C. In conclusion,the lost of ppk1 gene can affect the expression of the outer membrane protein and multidrug efflux systems encoding genes of ESBLs-UPEC, which increase the sensitivity of ESBLs-UPEC to various drugs.

Clocked atom delivery to a photonic crystal waveguide.

Experiments and numerical simulations are described that develop quantitative understanding of atomic motion near the surfaces of nanoscopic photonic crystal waveguides (PCWs). Ultracold atoms are delivered from a moving optical lattice into the PCW. Synchronous with the moving lattice, transmission spectra for a guided-mode probe field are recorded as functions of lattice transport time and frequency detuning of the probe beam. By way of measurements such as these, we have been able to validate quantitatively our numerical simulations, which are based upon detailed understanding of atomic trajectories that pass around and through nanoscopic regions of the PCW under the influence of optical and surface forces. The resolution for mapping atomic motion is roughly 50 nm in space and 100 ns in time. By introducing auxiliary guided-mode (GM) fields that provide spatially varying AC Stark shifts, we have, to some degree, begun to control atomic trajectories, such as to enhance the flux into the central vacuum gap of the PCW at predetermined times and with known AC Stark shifts. Applications of these capabilities include enabling high fractional filling of optical trap sites within PCWs, calibration of optical fields within PCWs, and utilization of the time-dependent, optically dense atomic medium for novel nonlinear optical experiments.

Utilisation of village clinics in Southwest China: evidence from Yunnan Province.

INTRODUCTION: Primary healthcare in rural China is underutilised, especially in village clinics in Southwest China. The aim of this study was to explore any relationships among the ethnicity of the healthcare provider, the clinical competence of the healthcare provider, and the utilisation of village clinics in Southwest China. METHODS: This cross-sectional survey study involved 330 village healthcare providers from three prefectures in Yunnan Province in 2017. Multiple logistic regressions were adopted to investigate the utilisation of primary healthcare among different ethnic healthcare providers. RESULTS: Primary healthcare utilisation was higher in village clinics where healthcare providers were Han Chinese than those where healthcare providers were ethnic minority (151 vs 101, P=0.008). The logistic regression analysis showed that clinical competence was positively associated with the utilisation of primary healthcare (odds ratio [OR]=1.49, 95% confidence interval [CI]=1.12-2.00; P=0.007) and that inadequate clinical competence of ethnic minority health workers may lead to a lag in the utilisation of primary healthcare (OR=0.45, 95% CI=0.23-0.89; P=0.022). CONCLUSION: Our results confirm differences in the utilisation of primary healthcare in rural Yunnan Province among healthcare providers of different ethnicities. Appropriate enhancements of clinical competence could be conducive to improving the utilisation of primary healthcare, especially among ethnic minority healthcare providers.

[Analysis of the relationship between syncope and poor prognosis in patients with acute pulmonary embolism and related factors].

Objective: To explore the association between syncope and poor prognosis and related factors of syncope in patients with acute pulmonary embolism (APE). Methods: A total of 740 patients with first diagnosed APE treated in West China Hospital of Sichuan University from September 1, 2016 to December 30, 2019 were enrolled. The basic information and clinical information (including clinical manifestations, complications, auxiliary examination, treatment and prognosis, etc.) of the patients were obtained from inpatient medical records. The patients were divided into the syncope group and the non-syncope group according to whether they had syncope or not. The basic and clinical conditions of the two groups were compared, and the factors related to syncope in APE patients were analyzed by multiple logistic regression model. Results: The proportion of APE patients with syncope was 12.6% (93/740). Age was (59±16) years in the syncope group (93 cases) and (59±17) years in the non-syncope group (647 cases), with 57.0% (53/93) and 60.4% (391/647) males, respectively. The body mass index, in-hospital mortality, proportions with high risk APE and mechanical ventilation of the syncope group were higher than those of the non-syncope group [(24.5±4.0) kg/m2 vs (23.3±3.8) kg/m2, 16.1% vs 7.7%, 4.4% vs 1.3% and 9.7% vs 2.5%, respectively]. The length of hospital stay [M (Q1, Q3)] of the syncope group was longer than that of the non-syncope group [15 (10, 22) d vs 14 (9, 22) d], and the proportions with chest pain and hemoptysis were lower than those of the non-syncope group (19.4% vs 36.8% and 14.0% vs 27.2%, respectively) (all P values<0.05). Multivariate logistic regression analysis showed that enlargement of the right heart [OR (95%CI): 2.46 (1.07, 5.64)] was a factor associated with syncope in APE patients. Conclusion: The proportion of APE patients with syncope is relatively high and is associated with poor prognosis, while enlargement of the right heart is associated with syncope in APE patients.

Effects of Wenyang Zhenshuai Granules on the Expression of Key Mitochondrial Autophagy Proteins in the Doxorubicin-Induced Model of H9c2 Cardiomyocyte Injury.

This study aimed to explore the effects of Wenyang Zhenshuai granules (WZG) on the morphology of cardiomyocytes, cell viability, and the expression of key mitochondrial autophagy proteins in the doxorubicin-induced model of H9c2 cardiomyocyte injury. Cardiomyocytes were cultured for 44 h and divided into 4 groups: intact control, doxorubicin-injured cells (DOX), doxorubicin-injured cells treated with WZG (DOX+WZG), and doxorubicin-injured cells treated with valsartan (DOX+valsartan; reference group). The morphology of cardiomyocytes was analyzed under an inverted microscope; cardiomyocyte survival rate was determined by MTT assay. The expression of the key mitochondrial autophagy proteins (PINK1, parkin, LC3-II, and prohibitin-2) was analyzed by Western blotting. WZG down-regulated the expression of the key mitochondrial autophagy proteins in DOX-injured cells, which may be one of the important mechanisms for regulating ventricular remodeling and cardiomyocyte apoptosis.

miR-34a-5p plays an inhibitory role in hepatocellular carcinoma by regulating target gene VEGFA.

OBJECTIVE: The objective of this research is to determine the role of miR-34a-5p in the occurrence and development of HCC by targeting VEGFA. METHODS: The expression of miR-34a-5p in HCC cell lines and tumour tissue was detected by qRT-PCR; the effect of miR-34a-5p on the invasive ability of HCC cells (SMMC7721 and MHCC97H) were detected by Transwell invasion assay; VEGFA is predicted as a potential target gene of miR-34a-5p by TargetScan, and validated with dual-luciferase reporter gene assay, qRT-PCR and western blot. VEGFA expression in HCC cell lines and tumour tissue was detected using qRT-PCR; the regulation and influence of miR-34a-5p and VEGFA on the proliferation, invasion, migration and the S-phase cell of HCC cells with different invasive abilities were detected by CCK8, Transwell assay, wound healing assay, and flow cytometry. The effect of miR-34a-5p on the growth of tumour was detected by constructing a xenograft model of nude mice with HCC. RESULTS: It was found that the expression of miR-34a-5p in HCC cells and tumour tissue was significantly decreased. Up-regulating miR-34a-5p expression could reduce the invasion ability of HCC cells. MiR-34a-5p could inhibit the mRNA and protein expression level of VEGFA via combining with the 3'-UTR of VEGFA. VEGFA was highly expressed in HCC cells and tumour tissues. The miR-34a-5p inhibited the proliferation, invasion, migration and S-phase arrest of HCC cells, but this inhibition effect could be neutralised by VEGFA; miR-34a-5p exerted the inhibitory effect on HCC cell proliferation and tumour growth in the HCC xenograft model of nude mice. CONCLUSION: These results suggest that miR-34a-5p could inhibit the occurrence and development of HCC by targeting VEGFA.

[Research advances in the treatment of liver failure with mesenchymal stem cell-derived exosomes].

Liver failure is a serious clinical syndrome in which multiple pathogenic factors exceed the liver's self-repair capability, resulting massive hepatocellular necrosis, rapid disease progression and high mortality. Liver transplantation is the most effective method for the treatment of liver failure, but it has disadvantages, such as insufficient liver donor and high cost. The clinical efficacy of mesenchymal stem cells in liver failure have been validated, but its application has been limited to certain extent. Cell-free-based therapies, especially mesenchymal stem cell-derived exosomes, has become a research hotspot in recent years. This paper reviews the research advances in the treatment of liver failure with the use of mesenchymal stem cell-derived exosomes.

[Meta analysis of rock salt aerosol therapy for respiratory tract diseases].

Objective: To systematically evaluate the efficacy and safety of rock salt aerosol in the treatment of respiratory tract diseases. Methods: In June 2021, the clinical randomized controlled trial literatures of rock salt aerosol therapy for respiratory tract diseases were searched from CNKI, Wanfang, VIP, Cochrane Library, PubMed database and EMBASE database. Cochrane risk bias evaluation tool was used to evaluate risk bias, Revman 5.4 and Stata16 were used to conduct meta-analysis, TSA 0.9 was used to conduct sequential analysis of trials, and gradepro was used to evaluate evidence quality. Results: A total of 21 literatures were included. According to whether the subjects received rock salt aerosol therapy, they were divided into the experimental group (1125 people) and the control group (973 people) . Compared with the control group, the total clinical effective rate (RR=1.22, 95%CI: 1.15~1.29, P<0.001) , forced expiratory volume in one second (FEV(1)) (WMD=0.20, 95%CI: 0.09~0.31, P<0.001) , percentage of FEV(1) in the predicted value (FEV(1)%) (WMD=5.06, 95%CI: 3.47~6.65, P<0.001) , forced vital capacity (FVC) (WMD=0.22, 95% CI: 0.16~0.27, P<0.001) , maximum expiratory flow (PEF) (WMD=21.312, 95%CI: 9.189~33.435, P=0.004) of experimental group were higher. TSA test shows that the difference conclusions of total effective rate, FEV(1), FEV(1)%, FVC and PEF were reliable, but the conclusion of FEV(1)% needs to be treated with caution; Three literatures reported the adverse reactions in the experimental group; GRADE evidence quality evaluation showed 3 very low-quality evidences and 2 low-quality evidences. Conclusion: Rock salt aerosol therapy combined with conventional therapy has a certain effect on the treatment of respiratory tract diseases, which needs to be further confirmed by high-quality evidence.