Objective To analyze the urban drinking water quality and its influencing factors in Anhui Province from 2014 to 2022, and to provide a scientific basis for water quality improvement and protection. Methods The data were collected, saved and monitored according to the Standard Test Method for Drinking Water (GB/T5750-2006) and evaluated according to the Hygienic Standard for Drinking Water (GB 5749-2006). Results A total of 20 941 samples were collected, and the overall qualified rate was 84.26%. The qualified rate of urban drinking water increased from 76.9% in 2014 to 93.3% in 2022, and the qualified rate of water quality was on the rise (χ²=544.43, P＜0.01). From 2014 to 2022, the qualified rate of water quality in dry season was higher than that in wet season (χ²=35.98, P<0.001), the qualified rate of surface water was higher than that of ground water (χ²=4440.8, P<0.001), and the qualified rate of peripheral tap water was higher than that of factory water (χ²=145.1, P<0.001). Among all kinds of disinfection methods, chlorination disinfection had the highest qualified rate (χ²=1483.8, P<0.001). The qualified rate of water quality increased with the increase of the scale of water plant. Among the inspected indicators, the main unqualified indicators were chlorine dioxide (7.72%), fluoride (7.41%), free residual chlorine (3.90%), and total bacterial count (2.13%). Conclusion The passing rate of urban drinking water quality in Anhui Province is on an upward trend, and the quality of urban drinking water has improved. However, it is still important to pay attention to the problem of excessive microorganism and fluoride in water, and the quality of drinking water varies from place to place.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. RESULTS: A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. CONCLUSION ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Circulating Tumor DNA/blood* ; High-Throughput Nucleotide Sequencing/methods* ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; Mutation/genetics* ; Aged ; Adult ; Aged, 80 and over

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

OBJECTIVE: Anemoside B4 (AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in vitro. METHODS: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8 (CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore, label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type I IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical staining. RESULTS: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein (N), Spike protein (S), and 3C-like protease (3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon (IFN)-β response via the activation of retinoic acid-inducible gene I (RIG-1) like receptor (RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA metabolism. CONCLUSION Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

Background::The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.Methods::This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.Results::The optimal cut-off values of L3-SMI were 39.50 cm 2/m 2 for male patients and 33.06 cm 2/m 2 for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis ( Wald = 6.347, P = 0.012). Conclusions::This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

Malignant tumors in children are one of the most important diseases that threaten the health and quality of life of children and are the second most common cause of death in children.With the continuous improvement and progress of treatment technology, the long-term survival rate of children with tumor has been significantly improved, but both the disease itself and the treatment can impair the immune function of children, which makes them vulnerable to various infectious diseases and secondary serious complications, and even become a source of infection, endangering the health of others. Vaccination is the most cost-effective measure to prevent infectious diseases. For children with normal immune functions, the benefits of vaccination usually outweigh the disadvantages. However, there is a lack of detailed data on the vaccination situation, efficacy and safety of vaccine use for such immunocompromised tumor survivors, and there are no authoritative and uniform vaccination recommendations. This article reviewed and summarized the literature and consensus of some domestic and foreign scholars on current status of post-treatment vaccination status, efficacy and safety of vaccination for children with tumors after treatment, with the aim of providing a reference for the practice in this field in China.

ObjectiveTo explore the effect and mechanism of the classic famous prescription Anmeidan （AMD） developed in the Qing Dynasty in regulating the hepatic neurotransmitters and circadian rhythm in the rat model of insomnia via the orexin-1 receptor （OX1R）/phosphatidylinositol-specific phospholipase Cβ-1 （PLCβ-1）/protein kinase Cα （PKCα）/extracellular signal-regulated kinase 1/2 （ERK1/2） signaling pathway. MethodSixty SPF-grade SD rats were randomized into blank， model， suvorexant （30 mg·kg^-1·d^-1）， and low-， medium-， and high-dose （4.55， 9.09， 18.09 g·kg^-1·d^-1， respectively） AMD groups， with 10 rats in each group. The rats in other groups except the blank group were modeled by intraperitoneal injection of p-chlorophenylalanine （PCPA） and administrated with corresponding drugs by gavage， and the blank group received an equal volume of normal saline. The general condition， body mass， and 24 h autonomic activity of each group were observed. The pathological changes of the liver tissue were observed by hematoxylin-eosin（HE）staining and Masson staining. The expression of gamma-aminobutyric acid （GABA）， 5-hydroxytryptamine （5-HT）， epinephrine （EPI）， norepinephrine （NE）， and acetylcholine （ACh） in the liver tissue was detected by enzyme-linked immunosorbent assay. The glutamate （Glu） expression in the liver tissue was detected by the biochemical method. The mRNA levels of biological clock genes Per1， Per2， Cry1， Cry2， Bmal1， and Bmal2 in the liver were determined by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. The protein and mRNA levels of factors in the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway in the liver were determined by Western blot and Real-time PCR， respectively. ResultCompared with the blank group， the modeling decreased the body mass （P<0.05， P<0.01） and caused mania and disturbed resting rhythms （P<0.01）， hepatic muscle fiber fracture， and edema with inflammatory cell infiltration. In addition， the modeling decreased the GABA， 5-HT， EPI， NE， and ACh content， increased Glu content （P<0.01）， down-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.01）， up-regulated the mRNA levels of Bmal1 and Bmal2 （P<0.01）， and promoted the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both protein and mRNA levels （P<0.01）. Compared with the model group， suvorexant and AMD increased the body mass （P<0.05， P<0.01）， alleviated the mania， and increased the resting time and frequency （P<0.05， P<0.01）. Moreover， the medications elevated the levels of GABA， 5-HT， EPI， NE， and ACh， lowered the Glu level， up-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.05， P<0.01）， down-regulated the mRNA levels of Bmal1 and Bmal2， and inhibited the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both mRNA and protein levels （P<0.05， P<0.01）. ConclusionAMD can regulate hepatic neurotransmitters and improve circadian rhythm in insomniac rats by inhibiting the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway， and high-dose AMD demonstrated the strongest effect.

Objective:To investigate the factors influencing the success of external cephalic version.Methods:Pregnant women who underwent an external cephalic version due to breech or transverse presentation by the same operator in the Third Affiliated Hospital of Zhengzhou University from July 2015 to July 2021 were selected as the study objects. Univariate analysis and logistic regression analysis were used to explore the clinical factors influencing the success of the external cephalic version. The receiver operating characteristic (ROC) curve was used to analyze the best cut-off value of gestational week and amniotic fluid index at the time of operation and to evaluate the predictive value of the influencing factors on the success of the external cephalic version.Results:(1) A total of 118 cases finally entered this study. Among the 118 cases,77 cases (65.3%) succeeded in the external cephalic version, among which the success rate was 49.1% (27/55) for primipara and 79.4% (50/63) for multipara. The vaginal delivery rate was 56.8% (67/118). (2) Complications occurred in 19 (16.1%) of the 118 cases. The main complications were abnormal fetal heart rate (13 cases, 11.0%), umbilical cord presentation, and fetal position reversion (two cases and 1.7% in each), and the serious complications were intrauterine fetal death and placental abruption (one case and 0.8% in each).The complication rate of patients with successful external cephalic version was 7.8% (6/77), which was lower than that of those who failed the external cephalic version [31.7%(13/41)] ( χ 2=11.33, P=0.001). (3) Multivariate analysis showed that gestational week at surgery before 38, amniotic fluid index >11.10 cm, and multipara were the factors affecting the success of the external cephalic version [ OR(95% CI)=0.561(0.351-0.897), 1.173(1.018-1.351) and 4.201(1.547-11.404), all P<0.05]. (4) The area under the ROC curve of the combination of the gestational week at surgery, amniotic fluid index, and parity was 0.744 (95% CI: 0.640-0.848, P<0.001), and the Youden index was 0.518, with a sensitivity of 70.0% and a specificity of 81.8%. Conclusion:Gestational weeks, amniotic fluid index, and multipara are related to the success of the external cephalic version, and the combination of the three has certain predictive power for the success of the surgery.

BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.