Objective To investigate the effect of dapagliflozin on myocardial work and energy metabolism in patients with heart failure with reduced ejection fraction(HFrEF)without type 2 diabetes mellitus(T2DM).Methods Patients with HFrEF without T2DM who visited Wuzhou People's Hospital from January 2021 to January 2022 were randomly divided into conventional group and dapagliflozin group(conventional treatment+dapagliflozin).After treatment(12 months),myocardial work[global work index(GWI),global constructed work(GCW),global wasted work(GW),and global work efficiency(GWE)],energy metabolism[(free fatty acids(FFA)and β-hydroxybutyric acid(β-HB)],traditional cardiac function[left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and left ventricular ejection fraction(LVEF)],clinical efficacy,prognosis[mortality,rehospitalization,and incidence of major adverse cardiovascular events(MACE)]and adverse reactions were compared between the two groups.Results A total of 128 patients with HFrEF without T2DM were enrolled,including 63 patients in the dapagliflozin group and 65 patients in the conventional group.After treatment,the LVEDD,LVESD,GWW,NT-pro BNP in the dapagliflozin group was significantly lower than that in the conventional group(P＜0.05),while the LVEF,GWI,GCW,GWE,β-HB acid and FFA were significantly higher than those in the conventional group(P＜0.05).The total effective rate and hypoglycemia rates in the dapagliflozin group were significantly higher than those in the conventional group(P＜0.05),and the rehospitalization rate and MACE rate were significantly lower than those in the conventional group(P＜0.05).There were no significant differences in mortality,renal adverse events,urinary tract infections and gastrointestinal symptoms between the two groups(P＞0.05).Conclusion Dapagliflozin has significant clinical efficacy in patients with HFrEF without T2DM,which can increase the serum levels of FFA and ketones,improve effective work,and reduce ineffective work,but it is necessary to be vigilant against hypoglycemia.

Objective To investigate the incidence,biochemical manifestations and genetic mutation features of glutaric acidemia type Ⅱ(GA-Ⅱ)in newborns in Quanzhou,Fujian province.Methods From January 2014 to December 2022,a total of 643 606 newborns were screened for inherited metabolic diseases by tandem mass spectrometry in the Quanzhou area.Suspected positive newborns with multiple acylcarnitine elevations were diagnosed by the MassARRAY assay and high-throughput sequencing technology.Results A total of 247 newborns showed multiple acylcarnitine elevations during the study period,and 19 newborns were diagnosed with GA-Ⅱ by genetic diagnosis.In addition,one newborn showed elevated levels of isovalerylcarnitine(C5),and was suspected to be isovaleric acidemia,which was confirmed with GA-Ⅱ by genetic diagnosis.Twenty newborns were eventually diagnosed with GA-Ⅱ,and the incidence of GA-Ⅱ in the study population was 1:32 180.Newborn screening results showed the concentrations of octanoylcarnitine(C8),decanoylcarnitine(C10)and dodecanylcarnitine(C12)were higher than the upper limit of the reference range,which were key indicators for screening GA-Ⅱ.Ten distinct electrontransfer flavoprotein dehydrogenase ETFDH gene mutations were found in patients with GA-Ⅱ,most of which were missense mutations.The most common ETFDH mutation was C.250G>A(p.A84T)with an allele frequency of 47.5％,followed by C.524G>A(R175H),C.998A>G(p.Y333C)and C.1657T>C(p.Y553H).Conclusion Newborn screening is an important approach for early detection of GA-Ⅱ,but patients with GA-Ⅱ may have atypical biochemical changes,and all newborns with abnormal newborn screening results should be subjected to high-throughput sequencing for genetic diagnosis.

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO₂, NO₂, CO, PM_2.5, PM₁₀, and maximum 8 h O₃ concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM_2.5, NO₂, SO₂, and O₃ were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM_2.5, NO₂, SO₂ and O₃ were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

Background The association between serum nickel (Ni) and oral cancer incidence is unclear and most of the previous studies were observational studies that did not control for confounding factors between groups. Objective To assess the correlation of serum Ni with oral cancer incidence based on propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Methods A cohort of 456 newly diagnosed oral cancer patients was recruited from the First Hospital of Fujian Medical University during November 2011 to May 2019, and residents ordered their health check-up in hospitals or local community health centers over the same period were selected as a control group, which included a total of 1410 participants. Serum Ni was evaluated by inductively coupled plasma mass spectrometry. Case-control pairs were selected using a 1:1 PSM (caliper value of 0.02), and the study subjects in the case group and control group were weighted for subsequent analysis by IPTW. The general characteristics of the study subjects were tested for equilibrium before and after matching by chi-square test and standardized mean difference (SMD). This was followed by exploring the potential nonlinear dose-response relationship between serum Ni and oral cancer using restricted cubic splines as well as analyzing the association between serum Ni and oral cancer incidence by conditional logistic regression and weighted logistic regression. Results After controlling for between-group covariates by PSM and IPTW, the dose-response curves demonstrated that the risk of developing oral cancer tended to decline and then increase with the increasing serum Ni level. The outcome of the analysis using PSM demonstrated that as compared to the control group, the risk of developing oral cancer in the 0.09-16.80 μg·L⁻¹ serum Ni group was negatively correlated with serum Ni level (OR=0.36, 95%CI: 0.24-0.54), whereas the risk of developing oral cancer in the >16.80 μg·L⁻¹ serum Ni group was positively correlated with serum Ni level (OR=5.43, 95%CI: 2.76-10.68). After applying IPTW, a negative association was found between the risk of oral cancer and serum Ni concentration within a serum Ni window ranging from 0.09 to 20.55 μg·L⁻¹ (OR=0.39, 95%CI: 0.29-0.52), while a positive association with an OR and 95%CI of 5.54 (3.62-8.49) for the Ni concentration > 20.55 μg·L⁻¹. Conclusion In this study, a J-shaped relationship between serum Ni concentration and the risk of developing oral cancer is found, which shows that high serum Ni concentration (>20.55 μg·L⁻¹) may be a risk factor for oral cancer.

A fast,reliable,and cost-effective liquid chromatography-tandem mass spectrometry method was established to determine the effects of the traditional Chinese medicine employed to treat coronavirus disease 2019,namely,Lianhua Qingwen granules,Huoxiang Zhengqi capsules,Jinhua Qinggan granules,Shufeng Jiedu capsules,and Angong Niuhuang pills,on the pharmacokinetics of lopinavir/ritonavir in rats.Blood samples were prepared using the protein precipitation method and atazanavir was selected as the internal standard(IS).Separation was performed on an Agilent ZORBAX eclipse plus C18(2.1 mm x 50 mm,1.8 μm)column using acetonitrile and water containing 0.1％formic acid as the mobile phase for gradient elution.The flow rate was 0.4 mL/min and the injection volume was 2 μL Agilent Jet Stream electrospray ionization was used for mass spectrometry detection under positive ion multiple reaction monitoring mode at a transition of m/z 629.3→447.3 for lopinavir,m/z 721.3→296.1 for rito-navir,and m/z 705.4→168.1 for the IS.The method showed good linearity in the concentration range of 25-2500 ng/mL(r=0.9981)for lopinavir and 5-500 ng/mL(r=0.9984)for ritonavir.The intra-day and inter-day precision and accuracy were both within±15％.Items,such as dilution reliability and residual effect,were also within the acceptable limits.The method was used to determine the effects of five types of traditional Chinese medicines on the pharmacokinetics of lopinavir/ritonavir in rats.The pharmaco-kinetic results showed that the half-life of ritonavir in the groups administered Lianhua Qingwen granules and Huoxiang Zhengqi capsules combined with lopinavir/ritonavir was prolonged by approx-imately 1.5-to 2-fold relative to that in the control group.Similarly,the pharmacokinetic parameters of lopinavir were altered.Overall,the results of this study offer important theoretical parameters for the effective clinical use of five types of traditional Chinese medicines combined with lopinavir/ritonavir to reduce the occurrence of clinical adverse reactions.

Objective:To investigate the application value of three-dimensional visualization technology in management of middle hepatic vein (MHV) processing in associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).Methods:The retrospective and descriptive study was conducted. The clinical data of 40 patients with right massive liver cancer or multiple right liver lesions who underwent ALPPS in the First Affiliated Hospital of Guangxi Medical University from November 2017 to August 2019 were collected. There were 34 males and 6 females, aged (44±9)years, with a range from 26 to 64 years. All patients underwent multi-slice computed tomography (CT) plain and enhanced scan of superior abdominal region before operation, and the data were transmitted to the liver visualization analysis software IQQA system with 1.5 mm thin-layer images to complete the three-dimensional reconstruction of the liver and its blood vessels. Patients were performed ALPPS based on results of three-dimensional reconstruction and intraoperative findings. Observation indicators: (1) results of preoperative three-dimensional reconstruction; (2) surgical situations; (3) follow-up. Follow-up was conducted using outpatient examinations and telephone interview to detect postopeartive survival of patients up to March 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were described as M (range). Count data were represented as absolute numbers. Results:(1) Results of preoperative three-dimensional reconstruction: 40 patients underwent three-dimensional reconstruction successfully, of which 37 clearly showed MHV, tumor location and relationship between them, 3 patients showed unclearly MHV and were classified based on two-dimensional images. Of the 40 patients, 12 had MHV classified as type A, 13 as type B, 9 as type C, and 6 as type D. Three-dimensional reconstruction of vessels showed 22 with umbilical veins and 9 with anterior veins. Of the 40 patients, 35 were predicted to preserve MHV, and 5 were predicted to resect MHV. Total estimated liver volume, tumor volume, and reserved liver volume were (1 012±119)cm 3, 600 cm 3(8-2 055 cm 3), (346±80)cm 3. The ratio of future liver remnant to standard liver volume was 34%±8%. (2) Surgical situations : 40 patients underwent the first-stage ALPPS, including 35 with preservation of MHV and 5 with resection of MHV, which was accorded with preoperative prediction. Thirty-four patients underwent the second-stage ALPPS, and 6 patients had failure to receive the second-stage ALPPS due to undificiency future liver remnant. The operation time and volume of intraoperative blood loss for 40 patients undergoing first-stage ALPPS were (350±79)minutes and 300 mL(range, 100-2 600 mL). Three patients received blood transfusion and no perioperative death occurred. There were 24 patients with grade A heptic insufficiency according to criteria of International StudyGroup of Liver Surgery (ISGLS) and 16 patients with grade B heptic insufficiency after the first-stage ALPPS. Twenty-eight patients had grade Ⅰ complications of Clavien-Dindo classification, including 17 with a small pleural effusion, 10 with a small pleural and abdominal effusion, 1 with hypoproteinemia; 8 patients had grade Ⅱ complications of Clavien-Dindo classification, including 5 with pneumonia, 1 with pneumonia combined with pleural and abdominal effusion, 1 with coagulation disorders, 1 with biliary fistula; 3 patients had grade Ⅲ complications of Clavien-Dindo classification, including 2 with pneumothorax and pneumonia, 1 with pneumothorax, pneumonia and coagulation disorders; 1 patient had grade Ⅳ complications of Clavien-Dindo classification as systemic inflammatory response syndrome. All patients with complications were improved after symptomatic treatment, anti infection, transfusion of fresh frozen plasma or drainage. For the 34 patients undergoing the second-stage ALPPS, the operation time and volume of intraoperative blood loss were (320±83)minutes and 500 mL(range, 200-6 000 mL). Twelve patients received blood transfusion. There were 12 patients with grade A heptic insufficiency according to criteria of ISGLS and 22 with grade B heptic insufficiency after the second-stage ALPPS. Eighteen patients had grade Ⅰ complications of Clavien-Dindo classification, including 11 with a small pleural effusion, 7 with a small pleural and abdominal effusion; 12 patients had grade Ⅱ complications of Clavien-Dindo classification, including 4 with pneumonia, 4 with coagulation disorders, 3 with massive abdominal effusion, 1 with biliary fistula; 3 patients had grade Ⅲ complications of Clavien-Dindo classification, including 1 with pneumothorax and pneumonia, 1 with massive pleural effusion, 1 with obstructive jaundice; 1 patient had grade Ⅳ complications of Clavien-Dindo classification as pneumonia and anemia. All patients with complications were improved after symptomatic treatment, anti infection, transfusion of fresh frozen plasma or drainage. (3) Follow-up: 40 patients were followed up for 2-35 months, with a median follow-up time of 17 months. The 6-month, 1-, and 2-year survival cases were 35, 26, 21 cases. Conclusion:Three-dimensional visualization technology can clearly show the MHV classification and its relationship with tumor location, which has an important guiding significance in the decision-making of MHV management in ALPPS.

Objective: To investigate the association between the time of neutrophils to the lowest and prognosis of patients with esophageal squamous cell carcinoma (ESCC) treated with non-operative therapy. Methods: The clinical data of 325 non-operative treated ESCC patients were collected in this study. The X-title software was applied to establish optimal threshold of neutrophil reduction to the lowest value. According to the optimal threshold, the patients were divided into early group (115 cases) and late group (210 cases). The clinical features and survival time of the two groups were compared, and the factors of prognosis were analyzed by Cox regression model with univariate and multivariate analysis. Results: The X-title software demonstrated the optimal cutoff values for the time of neutrophils to the lowest was 39 days. The median overall survival time was 21.0 months in the early group which was significantly higher than that in the late group (16.0 months). Multivariate Cox regression analysis showed that the treatment methods and the time of neutrophils to the lowest were independent factors for overall survival of patients with ESCC treated by non-surgical therapy. Compared with radiotherapy alone, concurrent chemoradiation could benefit the survival (HR=0.64, P=0.026). The prognosis of patients in the late group of neutrophils to the lowest (HR=1.38, P=0.038) was poor compared with the early group. Furthermore, stratified by treatment methods, the overall survival of two groups showed statistically significant difference only in patients received concurrent chemoradiation. The mortality risk in the late group was higher than that in the early group (HR=3.53, P=0.010). Conclusion The time of neutrophils to the lowest is an independent prognosis factor for non-operative treated ESCC patients. The prognosis of patients in the early group is better than that in the late group.

Objective: To identify the definition of heat wave based on mortality risk assessment in different regions of China. Methods: Daily mortality (from China Information System for Disease Control and Prevention) and meteorological data (from National Meteorological Information Center in China) from 66 counties with a population of over 200 000 were collected from 2006-2011. With the consideration of climate type and administrative division, China was classified as seven regions. Firstly, distributed lag non-linear model (DLNM) was used to estimate community-specific effects of temperature on non-accidental mortality. Secondly, a multivariate meta-analysis was applied to pool the estimates of community-specific effects to explore the region-specific temperature threshold and the duration for definition of heat wave. Results: We defined regional heat wave of Northeast, North, Northwest, East, Central and Southwest China as being two or more consecutive days with daily mean temperature higher than or equal to the P₆₄, P₇₁, P₈₅, P₆₇, P₇₅ and P₇₇ of warm season (May to October) temperature, respectively, while the thresholds of temperature were 21.6, 23.7, 24.3, 25.7, 28.0 and 25.3 ℃. The heat wave in South China was defined as five or more consecutive days with daily mean temperature higher than or equal to the P₉₃ (30.4 ℃) of warm season (May to October) temperature. Conclusion The region-specific definition of heat wave developed in our study may provide local government with the guidance of establishment and implementation of early heat-health response systems to address the negative health outcomes due to heat wave.

Objective To estimate the effect of daily diurnal temperature range (DTR) on mortality in different areas in China.Methods A time series study using the data collected from 66 areas in China was conducted,and Meta-analysis was used to analyze the estimates of associations between DTR and daily mortality.Modifying effects of extremely low and high DTR-mortality relationship by season and socioeconomic status (SES) were also evaluated respectively.Cumulative excess risk (CER) was used as an index to evaluate the effects.Results The information about 1 260 913 registered deaths were collected between 1 January 2006 and 31 December 2011,we found the relationship between extreme DTR and mortality was non-linear in all regions and the exposure-response curve was J-shaped.In central and south areas of China,the result indicated the obvious acute effect of extremely high DTR,and the mortality effect in central area (CER=5.1％,95％CI:2.4％-7.9％) was significant higher than that in south area (CER=4.5％,95％CI:1.7％-7.3％).Regarding to the modification of seasons,the cumulative mortality effect of DTR in cold season (CER=5.8％,95％CI:2.5％-9.2％) was higher than that in hot season (CER=3.1％,95％CI:1.1％-5.1％).Generally,deaths among the elderly (≥75 years) were associated more strongly with extremely high DTR.Conclusions The mortality effects of extremely DTR in different areas and seasons showed different characteristics,that in central area and in cold season it was significantly stronger.After modified by season and SES,DTRs were the greatest threat to vulnerable population,especially to the elderly (≥75 years).Therefore,more attention should be paid to vulnerable groups and protection measures should be taken according to the local and seasonal conditions.

Objective To evaluate the predictive value of neutrophil-to-lymphocyte ratio (NLR) and hemoglobinto-white blood cell ratio (HWR) prior to treatment in prognosis of non-operative esophageal squamous cell carcinoma (ESCC) patients.Methods From October 2009 to November 2014,a total of 362 non-operative ESCC patients were enrolled in this prospective study.x2 test was used to analyze the relationship between NLR,HWR and general clinical features;Univariate and multivariate Cox regression analysis was performed to evaluate the association between variables and prognosis of non-operative ESCC patients.Results The optimal cutoff level of 1.23 for NLR and 24.92 for HWR were identified by X-title software.x2 test indicated NLR was significantly associated with gender,tumor length,T stage,TNM stage and fasting blood glucose level.Moreover,univariate and multivariate analyses showed that high NLR and high HWR were all associated with a poor prognosis in non-operative ESCC.However,when patients were specifically stratified by treatment modus,subset analysis showed that NLR was only predictive of prognosis in the concurrent chemoradiotherapy group (HR =4.080,95％ CI:1.074-15.497,P =0.039),whereas the influence of HWR on prognosis was just existed in the sequential chemoradiotherapy group (HR =2.625,95％ CI:1.311-5.254,P =0.006).Conclusions In this investigation,we found that high NLR and high HWR were associated with poor prognosis in non-operative ESCC.