ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Phosphatase and tensin-homolog deleted on chromosome 10 (PTEN) is an important cancer suppressor gene. Its pathogenic mutation leads to PTEN hamartoma tumor syndrome (PHTS), a rare syndrome also known as Cowden syndrome, which is relevant to early-onset hereditary breast cancer (BC). In this paper, we report three patients with unilateral multicentric BC and synchronous and metachronous bilateral BC who harbored PTEN gene mutations, and summarize the clinical manifestations, pathological characteristics, diagnosis, treatment and follow-up outcomes to provide reference for management of PTEN gene mutation-related BC among the Cowden syndrome population.

Objective:To identify the risk factors and to construct a predictive model for early postnatal mortality (with the first 7 days of life) in extremely preterm infants.Methods:This retrospective study involved 244 extremely preterm infants with a gestational age of 22 to 27 weeks and 6 days, born at the Affiliated Hospital of Jining Medical College from January 2017 to December 2022. They were divided into an early survival group ( n=140) and an early mortality group ( n=84), based on survival for ≥7 days after birth. LASSO and logistic regression were used to select risk factors for early mortality. A nomogram predictive model was constructed using the R software program. The goodness-of-fit tests, area under the curve (AUC), calibration curves, and decision curves were used to evaluate its performance and clinical usefulness. Results:LASSO regression and multivariate logistic regression analyses showed that breech delivery ( OR=3.055, 95% CI: 1.125-8.296), intubation in the delivery room ( OR=4.320, 95% CI: 1.328-14.053), diagnosis of grade Ⅲ-Ⅳ neonatal respiratory distress syndrome within 6 h after birth ( OR=11.552, 95% CI: 3.056-43.677), and use of adrenaline in the delivery room ( OR=10.706, 95% CI: 1.454-78.816) were risk factors for early mortality in extremely preterm infants. Conversely, large gestation age ( OR=0.234, 95% CI: 0.125-0.436), antenatal administration of corticosteroids to promote fetal lung maturity ( OR=0.046, 95% CI: 0.014-0.145), and the use of pulmonary surfactant within 6 h after birth ( OR=0.021, 95% CI: 0.004-0.122) were protective factors against mortality. The goodness of fit test of the early death risk nomogram prediction model for extremely preterm infants indicates a good fit ( P=0.702). The AUC of the model was 0.963 (95% CI: 0.943-0.983), with a sensitivity of 0.904 (95% CI: 0.806-0.949), specificity of 0.892 (95% CI: 0.829-0.938), and accuracy of 0.880. Decision curve analysis indicated that a threshold probability>2% would yield a net benefit. Conclusions:Breech delivery, intubation in the delivery room, use of adrenaline in the delivery room, and the diagnosis of grade Ⅲ-Ⅳ neonatal respiratory distress syndrome within 6 h post-birth are independent risk factors for early mortality in extremely preterm infants. Large gestational age, antenatal administration of corticosteroids to promote fetal lung maturity and use of pulmonary surfactant within 6 h after birth are protective factors. The constructed prediction model based on the aforementioned factors can quantitatively, conveniently, and intuitively assess the risk of early mortality in extremely preterm infants.

The study is designed to observe the mechanism of Tongfu Xiefei Guanchang Solution(TFXF) in the treatment of acute lung injury(ALI) in rats by improving intestinal barrier and intestinal flora structure via p38 mitogen-activated protein kinase(p38 MAPK)/myosin light chain kinase(MLCK) signaling pathway. Sixty SPF-grade Wistar rats were randomly divided into the control(CON) group, lipopolysaccharide(LPS) group(7.5 mg·kg~(-1)), LPS + dexamethasone(DEX) group(3.5 mg·kg~(-1)), LPS + high-dose(HD)-TFXF group(14.74 g·kg~(-1)), LPS + middle-dose(MD)-TFXF group(7.37 g·kg~(-1)), and LPS + low-dose(LD)-TFXF group(3.69 g·kg~(-1)). ALI model of the rat was established by intraperitoneal injection of LPS. The lactate dehydrogenase(LDH) activity and total protein concentration in the bronchoalveolar lavage fluid(BALF) were measured; tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) levels in lung and colon tissue of rats were detected by enzyme linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe the pathological expression in the lung and colon tissue of rats. The mRNA expression of p38 MAPK, TNF-α, and IL-1β in rat lung tissue was determined by real-time fluorescence quantitative polymerase chain reaction(real-time PCR). Western blot was used to detect the protein expression related to the p38 MAPK/MLCK signaling pathway in the colon tissue of rats. 16S rRNA sequencing was used to detect changes in the composition and content of intestinal flora in rats, and correlation analyses were performed to explore the regulatory role of intestinal flora in improving ALI in rats. The results showed that compared with those in the LPS group, the histopathological scores of lung and colon tissue, LDH activity, and total protein concentration in BALF were significantly reduced in rats in all groups after drug administration. Except for the LPS + LD-TFXF group, the remaining groups significantly reduced the levels of TNF-α and IL-1β in the lung and colon tissue of rats. The protein expressions of phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK)/p38, phosphorylated myosin light chain(p-MLC)/myosin light chain 2(MLC2), and MLCK in colon tissue of rats in each drug administration group were significantly decreased. The mRNA expression levels of p38 MAPK, TNF-α, and IL-1β were significantly reduced in the LPS + HD-TFXF group. 16S rRNA sequencing results showed that the abundance of intestinal flora was significantly higher in the LPS + HD-TFXF group, and intestinal floras including Sobs, Shannon, and Npshannon were significantly higher. The β-diversity distribution of intestinal flora tends toward the CON group, and the abundance of Firmicutes was significantly higher. The abundance of Proteobacteria was significantly reduced; the abundance of Bacteroides was significantly reduced, and the abundance of Ruminococcus was significantly higher. The main species differences were Blautia, Roseburia＿sp＿499, and Butyricicoccus. TNF-α and IL-1β of lung tissue were negatively correlated with Muribaculaceae, unclassified norank＿f＿Eubacterium＿coprostanoligenes, and Ruminococcus and positively correlated with Bacteroides. Meanwhile, TNF-α and IL-1β of colon tissue were negatively correlated with unclassified norank＿f＿Eubacterium＿coprostanoligenes and Ruminococcus and positively correlated with Bacteroides. The predicted biological function of the flora was related to the biosynthesis of secondary metabolites, amino acid biosynthesis, sugar metabolism, and oxidative phosphorylation. The above studies show that TFXF can repair lung and colon tissue structure and regulate inflammatory factor levels by modulating the abundance and diversity of intestinal flora species in ALI rats. Its mechanism of action in ameliorating ALI in rats may be related to the inhibition of inflammation, improvement of intestinal mucosal permeability, and maintenance of intestinal flora homeostasis and barrier through the p38 MAPK/MLCK signaling pathway.
Animals ; Acute Lung Injury/genetics* ; Rats ; p38 Mitogen-Activated Protein Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Myosin-Light-Chain Kinase/genetics* ; Male ; Gastrointestinal Microbiome/drug effects* ; Rats, Wistar ; Signal Transduction/drug effects* ; Interleukin-1beta/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Lung/metabolism* ; Intestinal Mucosa/metabolism* ; Humans

This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.
Humans ; Diabetic Nephropathies/drug therapy* ; Nonprescription Drugs/therapeutic use* ; Qi ; Network Meta-Analysis ; Capsules ; Drugs, Chinese Herbal/therapeutic use* ; Tablets ; Diabetes Mellitus/drug therapy*

Abstract: Objective　To develop a real-time fluorescent quantitative RT-PCR (qRT-PCR) method for qualitative and quantitative Chikungunya virus (CHIKV) analysis. Methods Based on the systematic analysis of the genomic sequences of Chikungunya and its related arboviruses, the specific nucleic acid sequences for Chikungunya virus were screened and identified, and then the primers and TaqMan probe were designed. Meanwhile, the human GAPDH gene was used as an internal reference. The reaction system for qRT-PCR was systematically optimized by L9(34) orthogonal design, and a rapid detection method for Chikungunya by qRT-PCR based on TaqMan probe methods was established. The sensitivity, specificity, reproducibility, and coverage of the established method were analyzed in detail. The standard curve was made, and the absolute quantitative method was established using the cloned nucleic acid fragments as positive samples. Results　A real-time fluorescent quantitative RT-PCR assay was developed for the qualitative and quantitative analysis of Chikungunya virus. The reaction system included Chikungunya virus and reference internal gene specific primers and probe, RT/Taq enzyme mixture, reaction buffer, and negative and positive reference. The established method obtained positive results with the ROSS strain of ECSA subtype, LR2006 strain of IOL branch, 181/25 strain of Asian type and Dongguan 2010 epidemic strains of Chikungunya virus, but there was no cross-reaction with other 18 arboviruses belonging to Flaviviruses, Alphaviruses and Bunyavirus. The minimum detection limit of the established method was 5.80 copies/mL, and a linear relationship was observed between the amount of input plasmid DNA and fluorescence signal value over a range of 5.80×102 copies/mL to 5.80×1010 copies/mL, and the correlation coefficient was 0.999 5. The qRT-PCR amplification efficiency was 91%, and the intra-assay variations and inter-assay variations were 0.01-0.07 and 0.03-0.11, respectively. Conclusions　The TaqMan qRT-PCR method developed in this study can qualitatively and quantitatively detect Chikungunya virus rapidly with specificity and sensitivity, providing a technical method for the prevention and control of this viral disease.

OBJECTIVE: To analyze the clinical features of acute myeloid leukemia (AML)/high-risk myelodysplastic syndrome (MDS) patients aged over 60 years old. METHODS: The clinical data of 61 elderly newly diagnosed patients with AML and high-risk MDS who submitted to the Department of Hematology/Oncology of the First Affiliated Hospital of Tsinghua University from January 2009 to April 16, 2021 were retrospectively analyzed. These patients were divided into chemotherapy group (45 cases) and supportive treatment group (16 cases). The overall survival (OS) was analyzed by Kaplan-Meier method, and the prognostic factors of survival were analyzed by multivariate Cox regression. RESULTS: After 2 cycles of induction chemotherapy, the complete remission (CR) rate was 37.8% (17/45), and overall response rate was 62.2% (28/45) in the chemotherapy group. The median OS in the chemotherapy group and supportive treatment group was 11.3 (0.07-43) and 1.6 (0.33-7.72) months, respectively (P<0.001). The median OS in patients who reached CR or did not reach after 1 cycle of induction chemotherapy was 19.8 (10-30.63) and 8.17 (0.07-43) months, respectively (P<0.05), while after 2 cycles was 22.7 (4.2-43) and 7.26 (0.07-26) months, respectively (P<0.001). Univariate analysis showed that age > 80 years old, CCI score > 2, PS score > 2 and supportive treatment were the adverse prognostic factors for OS. Further multivariate analysis suggested that chemotherapy was the only independent prognostic factor for OS (HR=0.140, 95%CI: 0.048-0.409, P<0.001). In the chemotherapy group, univariate analysis showed that CCI score > 2 and failure to reach CR after induction chemotherapy were poor prognostic factors. Multivariate analysis showed that CCI score > 2 (HR=0.139, 95%CI: 0.050-0.384, P<0.001) and failure to achieve CR after induction chemotherapy (HR=0.103, 95%CI: 0.041-0.259, P<0.001) were the adverse prognostic factors for OS. The patients were tolerant to side-effect of chemotherapy. CONCLUSION Appropriate chemotherapy can prolong the survival of elderly patients with AML and high-risk MDS.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Middle Aged ; Prognosis ; Remission Induction ; Retrospective Studies

Objective:To explore the quality management strategy of clinical blood utilization by analyzing the quality control indexes of clinical blood transfusion in Hubei province from 2018 to 2020.Methods:The quality control indexes of clinical blood utilization in 244 secondary or above hospitals in Hubei province from 2018 to 2020 were investigated, including the number of professional and technical personnel per thousand units of blood transfusion, the internal quality control rate of blood transfusion compatibility test, the participation rate of external quality evaluation in blood transfusion compatibility test, the per capita blood consumption of discharged patients, and the development rate of autologous blood transfusion for patients undergoing surgery, and the differences of each index were compared and analyzed.Results:The indexes in Hubei province showed an increasing trend from 2018 to 2020, but there was no significant difference( P>0.05). The distribution of each index in Hubei province was unbalanced( P<0.05). The average blood consumption of discharged patients(0.13±0.14 U), the internal quality control rate of blood transfusion compatibility test(84.92%), the participation rate of external quality evaluation of blood transfusion compatibility test(93.65%) and the development rate of autologous blood transfusion(55.56%) in the tertiary hospitals were significantly higher than those in the secondary hospitals(0.09±0.10 U, 43.22%, 55.08%, 29.66%), while the number of professional and technical personnel of blood transfusion in thousand units(1.34±1.43) in the tertiary hospitals was significantly lower than that in secondary hospitals(2.41±2.39)( P<0.05). The average blood consumption of discharged patients(0.12±0.11 U), the participation rate of external quality evaluation of blood transfusion compatibility(82.18%) and the development rate of autologous blood transfusion(62.64%) in general hospitals were significantly higher than those in specialized hospitals(0.08±0.13 U, 68.57%, 27.14%), while the number of professional and technical personnel in thousand units of blood transfusion(1.44±1.60) was significantly lower than that in specialized hospitals(2.88±2.53)( P<0.05). The internal quality control rate(73.73%), the participation rate of external quality evaluation(87.10%) and the development rate of autologous blood transfusion(52.07%) in public hospitals were significantly higher than those in private hospitals(29.63%, 51.85%, 25.93%), however, the number of professional and technical personnel in blood transfusion(1.70±1.98) was lower than that in private hospitals(3.95±3.21)( P<0.05). Conclusions:The overall quality of clinical blood utilization in Hubei has been steadily increasing. However, the quality of clinical blood was not balanced among different areas. The overall clinical blood utilization quality of tertiary hospitals was significantly higher than the secondary hospitals, the general hospitals was significantly higher than the specialized hospitals, and the public hospitals was significantly higher than the private hospitals. The professional and technical personnel of blood transfusion in tertiary, general and public hospitals need to be strengthened.

AIM: To construct and validate a diagnostic model for early detection of keratoconus based on parameters in Sirius.METHODS: The study comprised of 46 early keratoconus eyes(including 20 right eyes and 26 left eyes in 34 patients)and 46 age- and gender-matched normal eyes(including the right eyes of 46 patients)in the prediction group. The predictive index was constructed using LASSO and Logistic regression analyses based on the topographic, pachymetric and aberrometry variables of Sirius. There were 23 early keratoconus eyes categorized as suspected keratoconus cases by Sirius(including 12 right eyes and 11 left eyes in 23 patients)and 23 age- and gender-matched normal eyes(including the right eyes of 23 patients)included in the application cohort. External validation of predictors was performed for the application cohort.RESULTS: Sirius Keratoconus Index(SKI)was calculated based on the minimum corneal thickness and symmetry index back of Sirius. Highest AUC values were obtained in the prediction group(AUC=0.932)after Logistic regression analysis. The cut-off value of SKI was set at 0.44. Then, the receiver operating characteristic(ROC)curve, calibration plot and nomogram of the diagnostic formula were analyzed for the prediction cohort in detail. Finally, the accuracy of the SKI was evaluated in the application cohort; the sensitivity was 91% and the specificity was 96%.CONCLUSION: SKI based on minimum corneal thickness and symmetry index back of Sirius is a simple and effective method for early detection of keratoconus in the preoperative screening for refractive surgery.

Objective: To assess the association of socioeconomic status with the burden of cataract blindness in terms of year lived with disability (YLD) rates and to determine whether ultraviolet radiation (UVR) levels modify the effect of socioeconomic status on this health burden. Methods: National and subnational age-standardized YLD rates associated with cataract-related blindness were derived from the Global Burden of Disease (GBD) study 2017. The human development index (HDI) from the Human Development Report was used as a measure of socioeconomic status. Estimated ground-level UVR exposure was obtained from the Ozone Monitoring Instrument (OMI) dataset of the National Aeronautics and Space Administration (NASA). Results: Across 185 countries, socioeconomic status was inversely associated with the burden of cataract blindness. Countries with a very high HDI had an 84% lower age-standardized YLD rate [95% confidence interval ( Conclusion Long-term high-UVR exposure amplifies the association of poor socioeconomic status with the burden of cataract-related blindness. The findings emphasize the need for strengthening UVR exposure protection interventions in developing countries with high-UVR exposure.
Blindness/etiology* ; Cataract/etiology* ; Female ; Global Burden of Disease/statistics & numerical data* ; Humans ; Male ; Quality-Adjusted Life Years ; Social Class ; Socioeconomic Factors ; Ultraviolet Rays/adverse effects*