Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.

Objective:To investigate the predictive value of the changes of platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) in the therapeutic efficacy of the neoadjuvant treatment for breast cancer.Methods:The clinical data of 72 breast cancer patients who received neoadjuvant therapy in Nantong Tumor Hospital between February 2020 and January 2022 were retrospectively analyzed and the changes of PLR and NLR before and after neoadjuvant therapy were also analyzed. The receiver operating characteristic (ROC) curves were used to assess the predictive value of PLR, NLR and their changes in pathological complete remission (pCR) after neoadjuvant therapy.Results:The area under the ROC curve of PLR and NLR before the treatment, the difference in PLR before and after the treatment (ΔPLR), the difference in NLR before and after the treatment (ΔNLR) in predicting pCR was 0.520, 0.505,0.724 and 0.686,and the corresponding cut-off value was 269.231, 2.559, -2.840 and -1.457; the patients were divided into high and low groups according to the cut-off values. NLR before the treatment was not correlated with clinicopathological characteristics (all P > 0.05),while PLR before the treatment was correlated with tumor size ( P = 0.029), and ΔPLR was correlated with progesterone receptor expression ( P = 0.025), human epidermal growth factor receptor 2 (HER2) expression ( P < 0.001), molecular subtype ( P < 0.001), N stage ( P = 0.002), clinical stage ( P = 0.002) and treatment modality ( P < 0.001). ΔNLR was associated with HER2 expression ( P = 0.002), molecular subtype ( P = 0.024), tumor size ( P = 0.007), neural invasion ( P = 0.006), N stage ( P = 0.006), clinical stage ( P = 0.016) and treatment modality ( P = 0.014). ΔPLR and ΔNLR were influencing factors for patients achieving pCR after neoadjuvant therapy (all P < 0.05). Conclusions:Stage Ⅲ invasive breast cancer patients with higher ΔPLR and ΔNLR after neoadjuvant therapy have better prognosis.

Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

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.

Objective:To investigate the effect of Shengxian decoction combined with irbesartan and atorvastatin on tranditonal Chinese medicine (TCM) efficacy, blood lipid levels and blood pressure variability in patients with hypertension.Methods:This study prospectively selected 80 cases of hypertension patients in Chuzhou First People's Hospital from March 2016 to March 2019 as the objects, and were randomly divided into observation group and control group with 40 cases in each group. The control group was treated with irbesartan and atorvastatin, and the observation group was treated with Shengxian decoction on the basis of the treatment. After the treatment, the TCM efficacy , related blood lipids and improvement of blood pressure variability of the two groups were compared.Results:The total effective rate of TCM syndrome in the observation group (92.5%) was significantly higher than that in the control group (70.0%), with statistically significant difference ( P<0.05); compared with before treatment, the systolic blood pressure (SBP) in both groups was significantly decreased ( P<0.05), but there was no significant difference in diastolic blood pressure (DBP) between the two groups before and after treatment ( P>0.05); there was no significant difference in SBP and DBP between the two groups after treatment ( P<0.05). Compared with that before treatment, 24 h standard deviation of systolic blood pressure (24 h SSD), day standard deviation of systolic blood pressure (dSSD) and night standard deviation of systolic blood pressure (nSSD) in the two groups were significantly decreased ( P<0.05), while there was no significant difference in 24 h standard deviation of diastolic blood pressure (24 h DSD), day standard deviation of diastolic blood pressure (dDSD) and night standard deviation of diastolic blood pressure (nDSD) between the two groups ( P>0.05). Compared with the control group, the levels of 24 h SSD, dSSD and nSSD in the observation group were significantly lower ( P<0.05), while there was no significant difference in 24 h DSD, dDSD, nDSD between the two groups ( P>0.05); after treatment, the levels of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) in the two groups were significantly decreased ( P<0.05), and the observation group was significantly lower than the control group ( P<0.05). Conclusions:Shengxian decoction is effective in treating blood stasis type hypertension, which can effectively improve blood pressure variability and blood lipid levels.

Objective To investigate the prevalence of iron deficiency(ID)and iron deficiency anemia (IDA) in pregnant women in urban areas of China. Methods The study was a national cross-sectional survey conducted from September 19th, 2016 to November 20th, 2016. According to the classification of the National Bureau of Statistics, all survey sites were set up in 6 regions of the country. Pregnant women were continuously selected using multistage stratified sampling. A total of 12 403 pregnant women were collected and examined for serum ferritin and hemoglobin levels. Results The median serum ferritin level during pregnancy was 20.60 μg/L(11.78-36.98 μg/L), the hemoglobin level was(118±12)g/L. With the progress of pregnancy, the levels of serum ferritin and hemoglobin decreased gradually. The median serum ferritin levels in the first, second trimester and third trimester were 54.30 μg/L(34.48-94.01 μg/L), 28.60 μg/L(16.40-50.52 μg/L), and 16.70 μg/L(10.20-27.00 μg/L)respectively(P<0.01). The mean hemoglobin levels were(127 ± 10)g/L,(119 ± 11)g/L and(117 ± 11)g/L respectively(P<0.01). The prevalence of ID in urban pregnant women was 48.16%(5 973/12 403), and IDA prevalence was 13.87% (1 720/12 403). The prevalence of IDA in the first, second trimester and third trimester were 1.96% (20/1 019), 8.40%(293/3 487)and 17.82%(1 407/7 897), respectively(P<0.01). The prevalence of standardized ID and IDA were significantly different in various regions of China(P<0.01). The standardized prevalence of ID were relatively higher in East China and Northeast China, 57.37% and 53.41% respectively, while it was the lowest in Southwest China, 30.51%. The standardized prevalence of IDA in South Central, Northwest, and East China were relatively high, 21.30%, 16.97% and 17.53% respectively, and the standardized prevalence of IDA in Southwest China was the lowest, 5.44%,the differents in various regions were significant(all P<0.01). Conclusion The current phenomenon of ID and IDA in pregnant women is still very common,and nutrition and health care during pregnancy should be strengthened.

Objective: To explore the effect of hepatitis C virus (HCV) on the expression of serine protease inhibitor Kazal1 (SPINK1) and its clinical implication. Methods: mRNA and protein expression of SPINK1 in Huh7.5.1 cells infected by HCV JFH-1 and the control cells were measured by RT-PCR and western blotting, SPINK1 levels in the cell supernatants and sera of HCV patients were measured by enzyme-linked immunosorbent assay (ELISA), the difference of SPINK1 levels between healthy controls and HCV patients was analyzed. Results: Expression of SPINK1 mRNA and protein was higher in Huh7.5.1 cells infected by HCV JFH-1 than in the control cells, serum SPINK1 levels was much higher in HCV patients than in healthy controls (P=0.016). Conclusions HCV can upregulate the expression of SPINK1.

OBJECTIVETo investigate the relationship between two polymorphisms immediately upstream of the cyclooxygenase 2 (COX2) gene and preeclampsia in a South West Han Chinese population.

METHODSBlood samples from 205 patients with preeclampsia and 276 normal pregnant women as controls from Han Chinese in Chengdu area were analyzed by polymerase chain reaction-restriction fragment length polymorphisms.

RESULTSG and A allele frequencies for -1195G>A site were 48.54% and 51.46% in the patient group, respectively, and 40.40% and 59.60% in the control group, respectively. G and C allele frequencies for -765G>C site were 94.15% and 5.85% in the case group, respectively, and 94.38% and 5.62% in the control group, respectively. The AA genotype and variant A allelic frequencies of the -1195G>A SNP were significantly lower in patients with preeclampsia than in the control group (P<0.05), and the odds ratio for the risk of preeclampsia was 0.665 (95% CI: 0.444-0.982) in women homozygous for the variant COX2 A allele ( x²=4.233, P=0.047). The genotype and allele frequencies of the -765G>C polymorphism in patients with preeclampsia and controls showed no significant differences (P>0.05). Additional subgroup analyses (mild vs severe preeclampsia) of the two polymorphisms failed to reveal significant correlation for either genotypic or allelic frequencies. Furthermore, there was no significant association between the polymorphisms and blood pressure levels in the patient or control groups.

CONCLUSIONCOX2 -1195A homozygosity is associated with a decreased risk for preeclampsia in a South West Han Chinese population. On the other hand, the -765G>C polymorphism has no effect.

Adult ; Alleles ; Blood Pressure ; Case-Control Studies ; China ; Cyclooxygenase 2 ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide ; Pre-Eclampsia ; enzymology ; genetics ; physiopathology ; Pregnancy ; Risk Factors

Objective To identify and evaluate the important risk factors for preeclampsia.Methods Databases of PubMed,Web of Science,Ovid CBM,China Knowledge Resource Integrated Database,Wanfang and VIP Database were searched from January 1,1990 to December 31,2012 to collect the cohort and case control studies involving the risk factors for preeclampsia.According to the inclusion and exclusion criteria,data of the included studies were extracted.Meta-analysis was performed using Stata 12.0 software with DerSimonian Laird model to calculate OR and its 95％CI of each risk factor.Results A total of 20 studies involving 53 393 patients in the research group and 1 197 773 cases in the control group were included.Fifteen risk factors for preeclampsia were investigated,including:history of preeclampsia (OR=10.27,95％CI:7.67-13.75),complication with chronic kidney diseases(OR=4.69,95％CI:1.94-11.33),history of chronic hypertension (OR-3.47,95％CI:2.39 5.04),multiple pregnancy (OR-2.98,95％CI:2.43-3.66),pre pregnancy body mass index (BMI) ≥ 25(OR=2.47,95％CI:1.97 3.09),maternal hyperglycemia(gestational diabetes and pre existing diabetes)(OR=2.84,95％CI:2.28-3.55),primiparity (OR=2.47,95％CI:2.12-2.82),physical work during pregnancy (OR=1.62,95％CI:1.30-2.02) ; family history of hypertension (OR=2.14,95％CI:1.84-2.50),basic diastolic blood pressure ≥ 70 mmHg (OR=2.17,95％CI:1.44-3.27),low education levels less than junior school (OR=1.69,95％CI:1.34 2.15),basic systolic blood pressure ≥ 120 mmHg (OR=2.31,95％CI:1.86-2.86),urinary tract infection (OR=1.96,95％CI:1.54-2.48),maternal age ≥ 35 or ≤ 20 years (OR=1.43,95％CI:1.29 1.57) and mental ademosyne (OR=1.35,95％CI:1.24-1.47).In addition,smoking before or during pregnancy was found to decrease the incidence of preeclampsia (OR-0.66,95％CI:0.56 0.79).Conclusions The main risk factors for preeclampsia are:history ofpreeclampsia,complication with chronic kidney diseases,history of chronic hypertension,multiple pregnancy,pre-pregnancy BMI ≥ 25,maternal hyperglycemia,primiparity,work during pregnancy and family history of hypertension.Smoking may decrease the incidence of preeclampsia.Nevertheless,more emphasis should be laid the adverse perinatal outcomes of smoking.

Objective: To investigate the effect of diabetes on the intensity of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a)-SUMOylation and SERCA2a activity of myocardium in experimental rats.
Methods: The 8 weeks old SD rats were divided into 2 groups, Diabetic group, with diet-induced type 2 diabetic rats and Control group, with normal rats. The systolic and diastolic cardiac functions were evaluated by echocardiography and left ventricular pressure measurement. The intensity of SERCA2a-SUMOylation was examined by co-immunoprecipitation and SUMOylation kit.
Results: Compared with Control group, Diabetic group had decreased systolic and diastolic cardiac functions, especially for diastolic function;decreased SERCA2a protein expression and intensity of SUMOylation;decreased SUMOylation E2 (Ubc9 ) protein expression. The protein levels of SUMO1, SAE1 and SAE2 were similar between 2 groups.
Conclusion: The intensity of SERCA2a-SUMOylation and Ubc9 decreased in diabetic myocardium which implies that SERCA2a-SUMOylation and Ubc9 were closely related to the damage of diabetic myocardium in experimental rats.