Spatial-temporal distribution of preterm birth in China, 1990-2020: A systematic review and modelling analysis.

BACKGROUND: Little is known about the long-term trends of preterm birth rates in China and their geographic variation by province. OBJECTIVES: To estimate the annual spatial-temporal distribution of preterm birth rates in China by province from 1990 to 2020. DATA SOURCES: We searched PubMed, EMBASE, Web of Science, CNKI, WANFANG and VIP from January 1990 to September 2023. STUDY SELECTION AND DATA EXTRACTION: Studies that provided data on preterm births in China after 1990 were included. Data were extracted following the Guidelines for Accurate and Transparent Health Estimates Reporting. SYNTHESIS: We assessed the quality of each survey using a 9-point checklist. We estimated the annual preterm birth risk by province using Bayesian multilevel logistic regression models considering potential socioeconomic, environmental, and sanitary predictors. RESULTS: Based on 634 survey data from 343 included studies, we found a gradual increase in the preterm birth risk in most provinces in China since 1990, with an average annual increase of 0.7% nationally. However, the preterm birth rates in Inner Mongolia, Hubei, and Fujian Province showed a decline, while those in Sichuan were quite stable since 1990. In 2020, the estimates of preterm birth rates ranged from 2.9% (95% Bayesian credible interval [BCI] 2.1, 3.8) in Inner Mongolia to 8.5% (95% BCI 6.6, 10.9) in Jiangxi, with the national estimate of 5.9% (95% BCI 4.3, 8.1). Specifically, some provinces were identified as high-risk provinces for either consistently high preterm birth rates (e.g. Jiangxi) or relatively large increases (e.g. Shanxi) since 1990. CONCLUSIONS: This study provides annual information on the preterm birth risk in China since 1990 and identifies high-risk provinces to assist in targeted control and intervention for this health issue.

The Role of NCS1 in Immunotherapy and Prognosis of Human Cancer.

The Neural Calcium Sensor1 (NCS1) is a crucial protein that binds to Ca2+ and is believed to play a role in regulating tumor invasion and cell proliferation. However, the role of NCS1 in immune infiltration and cancer prognosis is still unknown. Our study aimed to explore the expression profile, immune infiltration pattern, prognostic value, biological function, and potential compounds targeting NCS1 using public databases. High expression of NCS1 was detected by immune histochemical staining in LIHC (Liver hepatocellular carcinoma), BRCA (Breast invasive carcinoma), KIRC (Kidney renal clear cell carcinoma), and SKCM (Skin Cutaneous Melanoma). The expression of NCS1 in cancer was determined by TCGA (The Cancer Genome Atlas Program), GTEx (The Genotype-Tissue Expression), the Kaplan-Meier plotter, GEO (Gene Expression Omnibus), GEPIA2.0 (Gene Expression Profiling Interactive Analysis 2.0), HPA (The Human Protein Atlas), UALCAN, TIMER2.0, TISIDB, Metascape, Drugbank, chEMBL, and ICSDB databases. NCS1 has genomic mutations as well as aberrant DNA methylation in multiple cancers compared to normal tissues. Also, NCS1 was significantly different in the immune microenvironment, tumor mutational burden (TMB), microsatellite instability (MSI), and immune infiltrate-associated cells in different cancers, which could be used for the typing of immune and molecular subtypes of cancer and the presence of immune checkpoint resistance in several cancers. Univariate regression analysis, multivariate regression analysis, and gene enrichment analysis to construct prognostic models revealed that NCS1 is involved in immune regulation and can be used as a prognostic biomarker for SKCM, LIHC, BRCA, COAD, and KIRC. These results provide clues from a bioinformatic perspective and highlight the importance of NCS1 in a variety of cancers.

Discovery of novel hydroxyamidine based indoleamine 2,3-dioxygenase 1 (IDO1) and thioredoxin reductase 1 (TrxR1) dual inhibitors.

In order to take advantage of both immunotherapeutic and metabolic antitumor agents, novel dual indoleamine 2,3- dioxygenase 1 (IDO1) and thioredoxin reductase 1 (TrxR1) inhibitors were designed. Thioredoxin reductase 1 (TrxR1) is a main ROS modulator within CRC cells. Indoleamine 2,3-dioxygenase (IDO1) is crucial controller for tryptophan (Trp) metabolism that is also important for CRC immunotherapy. Herein, ten compounds 12a-j containing hydroxyamidine scaffold were designed, synthesized and evaluated for inhibitory activities against IDO1/TrxR1 enzyme and CRC cells. Among these compounds, the most active compound 12d (ZC0109) showed excellent and balanced activity against both IDO1 (IC50 = 0.05 µM) and TrxR1 (IC50 = 3.00 ± 0.25 µM) were selected for further evaluation. Compound ZC0109 exhibited good dual inhibition against IDO1 and TrxR1 both in vitro and in vivo. Further mechanistic studies reveal that, through IDO1 and TrxR1 inhibition by ZC0109 treatment, accumulated ROS effectively induced apoptosis and G1/S cell cycle arrest in cancer cells. In vivo evaluation demonstrated excellent anti-tumor effect of ZC0109 with the notable ability of promoting ROS-induced apoptosis, reducing kynurenine level in plasma and restoring anti-tumor immune response. Thus, ZC0109 represents a potential CRC therapy agent for further development.

Developing and validating a Chinese multimorbidity-weighted index for middle-aged and older community-dwelling individuals.

OBJECTIVE: To develop and validate an index to quantify the multimorbidity burden in Chinese middle-aged and older community-dwelling individuals. METHODS: We included 20,035 individuals aged 45 and older from the China Health and Retirement Longitudinal Study (CHARLS) and 19,297 individuals aged 65 and older from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Health outcomes of physical functioning (PF), basic and instrumental activities of daily living (ADL and IADL) and mortality were obtained. Based on self-reported disease status, we calculated five commonly used western multimorbidity indexes for CHARLS baseline participants. The one that predicted the health outcomes the best was selected and then modified through a linear mixed model using the repeated individual data in CHARLS. The performance of the modified index was internally and externally evaluated with CHARLS and CLHLS data. RESULTS: The multimorbidity-weighted index (MWI) performed the best among the five indexes. In the modified Chinese multimorbidity-weighted index (CMWI), the weights of the diseases varied greatly (range 0.2-5.1). The top three diseases with the highest impact were stroke, memory-related diseases and cancer, corresponding to weights of 5.1, 4.3 and 3.4, respectively. Compared with the MWI, the CMWI showed better model fits for PF and IADL with larger R2 and smaller Akaike information criterion, and comparable prediction performances for ADL, IADL and mortality (e.g. the same predictive accuracy of 0.80 for ADL disability). CONCLUSION: The CMWI is an adequate index to quantify the multimorbidity burden for Chinese middle-aged and older community-dwelling individuals. It can be directly computed via disease status examined in regular community health check-ups to facilitate health management.

Diabetes patients with comorbidities had unfavorable outcomes following COVID-19: A retrospective study.

BACKGROUND: Previous studies have shown that diabetes mellitus is a common comorbidity of coronavirus disease 2019 (COVID-19), but the effects of diabetes or anti-diabetic medication on the mortality of COVID-19 have not been well described. AIM: To investigate the outcome of different statuses (with or without comorbidity) and anti-diabetic medication use before admission of diabetic after COVID-19. METHODS: In this multicenter and retrospective study, we enrolled 1422 consecutive hospitalized patients from January 21, 2020, to March 25, 2020, at six hospitals in Hubei Province, China. The primary endpoint was in-hospital mortality. Epidemiological material, demographic information, clinical data, laboratory parameters, radiographic characteristics, treatment and outcome were extracted from electronic medical records using a standardized data collection form. Most of the laboratory data except fasting plasma glucose (FPG) were obtained in first hospitalization, and FPG was collected in the next day morning. Major clinical symptoms, vital signs at admission and comorbidities were collected. The treatment data included not only COVID-19 but also diabetes mellitus. The duration from the onset of symptoms to admission, illness severity, intensive care unit (ICU) admission, and length of hospital stay were also recorded. All data were checked by a team of sophisticated physicians. RESULTS: Patients with diabetes were 10 years older than non-diabetic patients [(39 - 64) vs (56 - 70), P < 0.001] and had a higher prevalence of comorbidities such as hypertension (55.5% vs 21.4%, P < 0.001), coronary heart disease (CHD) (9.9% vs 3.5%, P < 0.001), cerebrovascular disease (CVD) (3% vs 2.2%, P < 0.001), and chronic kidney disease (CKD) (4.7% vs 1.5%, P = 0.007). Mortality (13.6% vs 7.2%, P = 0.003) was more prevalent among the diabetes group. Further analysis revealed that patients with diabetes who took acarbose had a lower mortality rate (2.2% vs 26.1, P < 0.01). Multivariable Cox regression showed that male sex [hazard ratio (HR) 2.59 (1.68 - 3.99), P < 0.001], hypertension [HR 1.75 (1.18 - 2.60), P = 0.006), CKD [HR 4.55 (2.52-8.20), P < 0.001], CVD [HR 2.35 (1.27 - 4.33), P = 0.006], and age were risk factors for the COVID-19 mortality. Higher HRs were noted in those aged ≥ 65 (HR 11.8 [4.6 - 30.2], P < 0.001) vs 50-64 years (HR 5.86 [2.27 - 15.12], P < 0.001). The survival curve revealed that, compared with the diabetes only group, the mortality was increased in the diabetes with comorbidities group (P = 0.009) but was not significantly different from the non-comorbidity group (P = 0.59). CONCLUSION: Patients with diabetes had worse outcomes when suffering from COVID-19; however, the outcome was not associated with diabetes itself but with comorbidities. Furthermore, acarbose could reduce the mortality in diabetic.

SLC7A11 negatively associates with mismatch repair gene expression and endows glioblastoma cells sensitive to radiation under low glucose conditions.

The cystine/glutamate antiporter xCT (SLC7A11) is frequently upregulated in many cancers, including glioblastoma (GBM). SLC7A11-mediated cystine taken up is reduced to cysteine, a precursor amino acid for glutathione synthesis and antioxidant cellular defense. However, little is known about the biological functions of SLC7A11 and its effect on therapeutic response in GBM. Here, we report that the expression of SLC7A11 is higher in GBM compared with normal brain tissue, but is negatively associated with tumor grades and positively impacts survival in the bioinformatic analysis of TCGA and CGGA database. Additionally, a negative association between SLC7A11 and mismatch repair (MMR) gene expression was identified by Pearson correlation analysis. In the GBM cells with glucose-limited culture conditions, overexpression of SLC7A11 significantly decreased MMR gene expression, including MLH1, MSH6, and EXO1. SLC7A11-overexpressed GBM cells demonstrated elevated double-strand break (DSB) levels and increased sensitivity to radiation treatment. Taken together, our work indicates that SLC7A11 might be a potential biomarker for predicting a better response to radiotherapy in GBM.

First Report of Diaporthe hongkongensis Causing Fruit rot on Peach (Prunus persica) in China.

Peach [Prunus persica (L.) Batsch] is an important deciduous fruit tree in the family Rosaceae and is a widely grown fruit in China (Verde et al., 2013). In July and August 2018, a fruit rot disease was observed in a few peach orchards in Zhuzhou city, the Hunan Province of China. Approximately 30% of the fruit in more than 400 trees was affected. Symptoms displayed were brown necrotic spots that expanded, coalesced, and lead to fruit being rotten. Symptomatic tissues excised from the margins of lesions were surface sterilized in 70% ethanol for 10 s, 0.1% HgCl2 for 2 min, rinsed with sterile distilled water three times, and incubated on potato dextrose agar (PDA) at 26°C in the dark. Fungal colonies with similar morphology developed, and eight fungal colonies were isolated for further identification. Colonies grown on PDA were grayish-white with white aerial mycelium. After an incubation period of approximately 3 weeks, pycnidia developed and produced α-conidia and ß-conidia. The α-conidia were one-celled, hyaline, fusiform, and ranged in size from 6.0 to 8.4 × 2.1 to 3.1 µm, whereas the ß-conidia were filiform, hamate, and 15.0 to 27.0 × 0.8 to 1.6 µm. For molecular identification, total genomic DNA was extracted from the mycelium of a representative isolate HT-1 and the internal transcribed spacer region (ITS), ß-tubulin gene (TUB), translation elongation factor 1-α gene (TEF1), calmodulin (CAL), and histone H3 gene (HIS) were amplified and sequenced (Meng et al. 2018). The ITS, TUB, TEF1, CAL and HIS sequences (GenBank accession nos. MT740484, MT749776, MT749778, MT749777, and MT749779, respectively) were obtained and in analysis by BLAST against sequences in NCBI GenBank, showed 99.37 to 100% identity with D. hongkongensis or D. lithocarpus (the synonym of D. hongkongensis) (Gao et al., 2016) (GenBank accession nos. MG832540.1 for ITS, LT601561.1 for TUB, KJ490551.1 for HIS, KY433566.1 for TEF1, and MK442962.1 for CAL). Pathogenicity tests were performed on peach fruits by inoculation of mycelial plugs and conidial suspensions. In one set, 0.5 mm diameter mycelial discs, which were obtained from an actively growing representative isolate of the fungus on PDA, were placed individually on the surface of each fruit. Sterile agar plugs were used as controls. In another set, each of the fruits was inoculated by application of 1 ml conidial suspension (105 conidia/ml) by a spray bottle. Control assays were carried out with sterile distilled water. All treatments were maintained in humid chambers at 26°C with a 12-h photoperiod. The inoculation tests were conducted twice, with each one having three fruits as replications. Six days post-inoculation, symptoms of fruit rot were observed on inoculated fruits, whereas no symptoms developed on fruits treated with agar plugs and sterile water. The fungus was re-isolated and identified to be D. hongkongensis by morphological and molecular methods, thus fulfilling Koch's Postulates. This fungus has been reported to cause fruit rot on kiwifruit (Li et al. 2016) and is also known to cause peach tree dieback in China (Dissanayake et al. 2017). However, to our knowledge, this is the first report of D. hongkongensis causing peach fruit rot disease in China. The identification of the pathogen will provide important information for growers to manage this disease.

Different outcome of COVID-19 in members of a family.

We report a family cluster of cases of coronavirus disease 2019 (COVID-19), in which three members of the family were exposed to SARS-CoV-2 at the same time, but the disease manifested differently among the three family members. We describe the clinical manifestations, disease progression, and treatment of wife and husband. We also analyze the daughter who was in close contact with patients with COVID-19 but was not infected.

Automated Modal Analysis for Tracking Structural Change during Construction and Operation Phases.

The automated modal analysis (AMA) technique has attracted significant interest over the last few years, because it can track variations in modal parameters and has the potential to detect structural changes. In this paper, an improved density-based spatial clustering of applications with noise (DBSCAN) is introduced to clean the abnormal poles in a stabilization diagram. Moreover, the optimal system model order is also discussed to obtain more stable poles. A numerical simulation and a full-scale experiment of an arch bridge are carried out to validate the effectiveness of the proposed algorithm. Subsequently, the continuous dynamic monitoring system of the bridge and the proposed algorithm are implemented to track the structural changes during the construction phase. Finally, the artificial neural network (ANN) is used to remove the temperature effect on modal frequencies so that a health index can be constructed under operational conditions.

Structural Health Monitoring of a Prestressed Concrete Bridge Based on Statistical Pattern Recognition of Continuous Dynamic Measurements Over 14 Years.

This work describes a vibration-based structural health monitoring of a prestressed-concrete box girder bridge on the A100 Highway in Berlin by applying statistical pattern recognition technique to a huge amount of data continuously collected by an integrated monitoring system during the period from 2000 to 2013. Firstly, the general condition and potential damage of the bridge is described. Then, the dynamic properties are extracted from 20 velocity sensors. Environmental variability captured by five thermal transducers and traffic intensity approximately estimated by strain measurements are also reported. Nonlinear influences of temperature on natural frequencies are observed. Subsequently, the measurements during the first year are used to build a baseline health index. The multiple linear regression (MLR) method is used to characterize the nonlinear relationship between natural frequencies and temperatures. The Euclidean distance of the residual errors is calculated to build a statistical health index. Finally, the indices extracted from the following years gradually deviate; which may indicate structural deterioration due to loss of prestress in the prestressed tendons.

Changes in digestive enzyme activities during larval development of Chinese loach Paramisgurnus dabryanus (Dabry de Thiersant, 1872).

The digestive physiology of Chinese loach (Paramisgurnus dabryanus) was studied by assessing the specific and total activities of different pancreatic (trypsin, chymotrypsin, amylase and lipase), gastric (pepsin) and intestinal (alkaline phosphatase and leucine-aminopeptidase) enzymes from hatching to 40 days after hatching (DAH). Larvae were reared at 24.4 ± 0.4 °C and fed with rotifers from mouth opening (4 DAH) to 15 DAH, from 10 to 35 DAH with Cladocera and from 30 to 40 DAH with compound diet. Enzyme activities for trypsin, chymotrypsin, amylase and lipase were detected before the onset of exogenous feeding, indicating that these enzymes were genetically pre-programmed. Most of the pancreatic enzyme specific activities increased until 20 DAH and decreased thereafter. The pepsin activity of Chinese loach was firstly detected at 30 DAH, indicating the appearance of functional gastric gland. Alkaline phosphatase specific activity was detected from hatching onward, showed marked increase and reached the second peak at 20 DAH, while a gradual increase in specific leucine-aminopeptidase activity was observed until the end of the experiment. Accordingly, the larvae of Chinese loach possess a functional digestive system before the onset of exogenous feeding and the digestive capacity gradually increases as development progresses. The abrupt increase in intestinal enzyme activities between 10 and 20 DAH demonstrates onset of juvenile-like digestive mode in Chinese loach larvae. The increase in pepsin activity after 30 DAH indicates the shift from alkaline to acidic digestion in Chinese loach larvae, which may be considered as the onset of weaning.

[Effect of short-hairpin RNA expression vector-mediated osteopontin RNA interference on proliferation and invasion of prostate cancer PC-3 cells].

BACKGROUND AND OBJECTIVE: Studies showed that osteopontin (OPN) regulates cell migration and invasion in a variety of cancers, which associates with the activities of matrix metalloproteinase (MMP)-2 and MMP-9. This study was to investigate the role of OPN in the proliferation and invasion of human prostate cancer PC-3 cells and the possible functions of IgammaB kinase (IKK) in nuclear factor kappa B (NF-kappaB)-mediated signaling pathways. METHODS: OPN short-hairpin RNA (shRNA) recombinant plasmids were transfected into PC-3 cells and different concentrations of IKK inhibitors were used to inhibit the activities of IKKalpha and IKKbeta. The mRNA and protein expression levers of OPN, MMP-2, and MMP-9 were detected by real-time polymerase chain reaction (PCR) and Western blot. Cell cycle was detected by flow cytometry, cell proliferation by MTT assay, and cell invasion by Transwell chamber assay. RESULTS: Compared with untreated cells, the protein levers of OPN, MMP-2, and MMP-9 in OPN shRNA-transfected PC-3 cells were reduced by 55.22%, 51.71%, and 28.35%, respectively, and the ability of cell migration and invasion were decreased by 45.48% and 51.96%, respectively (P<0.05). Moreover, the inhibition of IKKbeta inhibited the expressions of MMP-2 and MMP-9. CONCLUSION: A shRNA expression vector-mediated OPN gene silencing can inhibit the malignant biological behaviors of PC-3 cells. IKKbeta may play a crucial role in the OPN-induced activation of MMP-2 and MMP-9 via NF-kappaB-mediated IkappaB/IKKbeta pathways.

[Regulation of rat airway smooth muscle cell proliferation by mitochondrial ATP-sensitive K(+) channel in asthmic rats.].

The objective of this paper was to investigate the effect and mechanism of mitochondrial ATP-sensitive K(+) (MitoK(ATP)) channel on the proliferation of airway smooth muscle cells (ASMCs) in asthmic rats. Thirty-six Sprague-Dawley (SD) rats were randomly assigned into 2 groups (18 in each): (1) Asthma group: the asthmic rat model was established by ovalbumin (OVA) sensitization and excitation; (2) Normal group: rats were subjected to inhalation of equal amount of normal saline. The rat ASMCs were isolated from fresh lung tissues and cultured respectively as follows: (1) CONTROL GROUP: normal ASMCs were cultured under normoxia for 24 h; (2) Diazoxide group: normal ASMCs were cultured under normoxia for 24 h with diazoxide (an opener of MitoK(ATP) channel); (3) 5-HD group: normal ASMCs were cultured under normoxia for 24 h with 5-hydroxydecanoate (5-HD) (an antagonist of MitoK(ATP) channel); (4) Asthma group: Asthmic ASMCs were cultured under normoxia for 24 h; (5) Asthma + diazoxide group: Asthmic ASMCs were cultured under normoxia with diazoxide for 24 h; (6) Asthma + 5-HD group: Asthmic ASMCs were cultured under normoxia with 5-HD for 24 h. The mitochondrial membrane potential (ΔΨm) was detected using Rhodamine 123 (R-123). The level of reactive oxygen species (ROS) was detected by DCF fluorescence. The expression of nuclear factor-kappa B (NF-κB) mRNA was examined by RT-PCR. The proliferation and apoptosis of rat ASMCs were examined respectively by MTT colorimetric assay and cell cycle analysis. The results were as follows. (1) After exposure to diazoxide for 24 h, the R-123 fluorescence intensity, the ROS level, NF-κB mRNA expression and the MTT absorbance value (A value) in normal ASMCs were significantly increased, and the apoptosis of rat ASMCs was significantly decreased compared to the control group (P<0.05). However, there was no significant changes in those indices after the normal ASMCs had been exposed to 5-HD for 24 h. (2) In Asthma and Asthma + diazoxide groups, the R-123 fluorescence intensity, ROS level and the MTT A value were markedly increased, and the apoptosis was markedly decreased compared to control group (P<0.05). These changes were more obvious in Asthma + diazoxide group than those in Asthma group (P<0.05). 5-HD partly weakened the effect of asthma on the R-123 fluorescence intensity, ROS level and the MTT A value and the apoptosis of rat ASMCs (P<0.05). R-123 fluorescence intensity and NF-κB mRNA expression were positively correlated with ROS level. NF-κB mRNA expression was positively correlated with the MTT A value and negatively correlated with the apoptosis of rat ASMCs. All the results suggest that the opening of MitoK(ATP) channel followed by a depolarization of ΔΨm contributes to the increase in ROS level and NF-κB mRNA expression in rat ASMCs and to the unbalance between cell proliferation and apoptosis of ASMCs induced by asthma. This might be a mechanism of the development of airway remodeling in asthma.