Objective To investigate the levels of gross α and gross β activities in different water types within a 40-kilometer radius around the Zhangzhou Nuclear Power Plant prior to its operation. Methods In 2018, drinking water samples were collected from the area surrounding the nuclear power plant during both the wet and dry seasons, including source water, treated water, tap water, and well water. The gross α and gross β activity concentrations were measured using a low-background α/β counter, followed by statistical analysis. Results A total of 80 water samples from different sources around the Zhangzhou Nuclear Power Plant were collected. The average gross α and gross β activity concentrations during the wet season were (0.110 ± 0.036) Bq/L and (0.643 ± 0.028) Bq/L, respectively, while those during the dry season were (0.124 ± 0.032) Bq/L and (0.624 ± 0.026) Bq/L, respectively. There were no significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for the overall sample set (P > 0.05). However, there were statistically significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for source water and well water (Z_wet = −2.005, −2.123; Z_dry = −1.943, −3.090; P < 0.05). Conclusion The radioactivity levels in different water types within various ranges around the Zhangzhou Nuclear Power Plant before its operation were determined. The measured activity concentrations were at the same level as those from previous investigations in other regions of Fujian Province.

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

OBJECTIVE To observe the anti-influenza effect of Jiawei Xiangru oral liquid through MDCK cells and mice, and predict its therapeutic mechanism for influenza based on network pharmacology. METHODS Observed the effect of different concentrations of Jiawei Xiangru oral liquid on MDCK cell damage caused by influenza A virus type 3 and its protective effect on influenza virus infected mice. The effective ingredients and action targets of each drug were collected through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Collect influenza disease related targets using GeneCards 5.14, OMMI and other databases, and construct a network diagram. Build PPI network diagrams, GO enrichment, and KEGG pathway analysis using STRING and Metascape databases. Complete molecular docking and 3D visualization display using AutoDockTools and PyMOL software. RESULTS In vitro experiments shown that the Jiawei Xiangru oral liquid had a significant inhibitory effect on MDCK cell damage and hemagglutination caused by influenza virus. In vivo experiments shown that it could prolong the survival time of mice infected with influenza A virus, improve the death protection rate of mice infected with the virus, and reduce the lung index and lung tissue virus titer of mice. The 82 active ingredients and 168 common targets were screened, with carotenoid, folic acid, 3'- methoxy daidzein, coellitin, and kaempferol as key components, and TNF, AKT1, EGFR, STAT3, SRC, MMP9, and PTGS2 as core targets. KEGG pathway enrichment analysis showed that the main mechanism of action maight exert anti-influenza virus effects through the TNF signaling pathway, chemokine signaling pathway, PI3K/Akt signaling pathway, and VEGF signaling pathway. CONCLUSION Pharmacodynamics have shown that the Jiawei Xiangru oral liquid can effectively treat influenza diseases, and its mechanism maybe related to the synergistic regulation of "multi components, multi targets, and multi pathways".

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To investigate the application value of single nucleotide polymorphism(SNP)linkage analysis based on next-generation sequencing(NGS)technology in preimplantation genetic testing(PGT)of families with autosomal recessive polycystic kidney disease(ARPKD).Methods A family with ARPKD was selected,where the female member had a pregnancy ultrasound revealing polycystic kidney in the fetus.Genetic testing showed compound heterozygous mutations of the polycystic kidney/polycystic liver disease 1 gene(PKHD1),c.10444C>T(paternal)and c.4303del(maternal),with the c.4303del mutation being reported for the first time.Targeting the coding region of the PKHD1 gene,335 high-density tightly linked SNP sites were selected in the upstream and downstream 2M regions using multiplex polymerase chain reaction(PCR)and NGS.The couple′s SNP risk haplotypes carrying gene mutations were constructed.After in vitro fertilization,blastocyst culture was performed.Trophoblastic cells obtained from the biopsy were subjected to whole-genome amplification,and NGS was used for linkage analysis and low-depth chromosomal aneuploidy screening of the embryos.Sanger sequencing was used to verify the results of embryo linkage analysis.Results Among the 6 biopsied embryos,4 were mutation-free and euploid,1 exhibited heterozygous for the mutation and mosaic while another unstable sequencing data,making it impossible to judge.One of the mutation-free and developmentally healthy euploid embryos was implanted into the maternal uterus,resulting in the full-term delivery of a healthy baby.Conclusion Application of NGS-based SNP linkage analysis in PGT can effectively blocking the vertical transmission of ARPKD within families,while avoiding abortion issues caused by aneuploid embryos.This study is also the first PGT report target-ing the PKHD1 gene c.4303del mutation.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Objective:To investigate the specimen quality of intersphincteric resection with transabdominal transanal mixed approach for rectal cancer in the Chinese Transanal Total Mesorectal Excision Registry Collaborative (CTRC) database.Methods:The retrospective case-control study was conducted. Based on the concept of real-world research, the clinicopathological data of 281 pati-ents with rectal cancer in the CTRC database who underwent intersphincteric resection with trans-abdominal transanal mixed approach in 19 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15,2017 to December 31,2023 were collected. There were 196 males and 85 females, aged 61(range, 27-87)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations; (4) analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resec-tion for rectal cancer. Measurement data with normal distribution were represented as Mean±SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The chi-square test was used for univariate analysis. Logistic regression model was used for multivariate analysis. Results:(1) Preoperative examinations. Of the 281 patients, 234 cases underwent preoperative pelvic magnetic resonance imaging (MRI) examina-tion. There were 2 cases in clinical stage T0, 3 cases in clinical stage T1, 58 cases in clinical stage T2, 137 cases in clinical stage T3, 24 cases in clinical stage T4, 3 cases in clinical stage Tx, 7 cases missing clinical T staging data. There were 87 cases in clinical stage N0, 68 cases in clinical stage N1, 60 cases in clinical stage N2, 9 cases in clinical stage Nx, 10 cases missing clinical N staging data. There were 30 cases with mesorectal fascia invasion, 53 cases with extramural venous invasion. The distance from lower margin of tumor to anal margin was 41.9(range, 1.0-80.0)mm. (2) Neoadjuvant therapy. Of the 281 patients, 125 cases underwent neoadjuvant therapy, including 39 cases receiving chemo-therapy alone, 6 cases receiving short-course simultaneous chemoradiotherapy, 5 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 48 cases receiving long-course simultaneous chemoradiotherapy, 2 cases receiving other treatments, and 25 cases missing neoadju-vant therapy data. (3) Postoperative examinations. Of the 281 patients, 249 cases achieved R 0 resection, 9 cases achieved R 1 resection, and there were 23 cases missing surgical margin data. The maximum tumor diameter, the number of lymph nodes harvested and positive rate of vessel carcinoma embolus were 30.0(range, 0.5-200.0)mm, 13(range, 0-70) and 27.55%(73/265) in 281 patients. There were 252 patients with circumferential margin records, showing positive in 15 cases, with a positive rate as 5.95%(15/252). The minimum distance from deep part of tumor to circumferential margin was 7.0(range, 0-150.0)mm in 252 patients. There were 85 cases with distal margin records, showing positive in 1 case, and the distance from lower margin of tumor to distal margin was 10.0(range, 0-202.0)mm. There were 273 patients with specimen integrity records, which showed intact specimen in 208 cases, fair specimen in 58 cases, poor specimen in 4 cases, unevaluated specimen in 3 cases. There were 7 cases with rectal perforation. Of the 281 patients, cases in pathological stage T0, Tis, T1, T2, T3, T4 were 14, 5, 22, 107, 113, 12, respectively, and there were 8 cases missing pathological T staging data. Of the 281 patients, cases in pathological stage N0, N1a, N1b, N1c, N2a, N2b were 176, 27, 27, 11,20, 12, respectively, and there were 8 cases missing pathological N staging data. Of the 281 patients, there were 4 cases with distant metastasis, 262 cases without distant metastasis, 5 cases not evaluated, and 10 cases missing tumor metastasis data. Of the 125 patients undergoing neoadjuvant therapy, there were 85 cases with tumor regression grade records, including 16 cases as grade 1, 27 cases as grade 2, 19 cases as grade 3, 15 cases as grade 4, 8 cases as grade 5. (4) Analysis of influencing factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer. Results of univariate analysis showed that preoperative T staging on preoperative pelvic MRI, mesorectal fascia invasion, extramural venous invasion, pathological T staging, and pathological N staging were related factors for positive circumferential margin in surgical specimen of intersphincteric resection for rectal cancer ( P<0.05). Conclusions:Intersph-incteric resection with transabdominal transanal mixed approach has good specimen quality and low positive rate of surgical margin. T staging on preoperative pelvic MRI may be related to positive circumferential margin after intersphincteric resection for rectal cancer.