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

The adulteration and counterfeiting of herbal ingredients in medicinal and food homology (MFH) have a serious impact on the quality of herbal materials, thereby endangering human health. Compared to pharmaceutical drugs, health products derived from traditional Chinese medicine (TCM) are more easily accessible and closely integrated into consumers' daily life. However, the authentication of the authenticity of TCM ingredients in MFH has not received sufficient attention. The lack of clear standards emphasizes the necessity of conducting systematic research in this area. This study utilized DNA barcoding technology, combining ITS2, psbA-trnH, matK as universal barcode sequences, and DX, HH, JYH as specific barcode sequences, to identify the authenticity of commercial medicinal and food homology scented herbal teas. The aim was to investigate the authenticity of scented herbal tea products circulating in the market. The research results revealed that among 180 scented herbal tea samples, DNA barcodes were successfully obtained from 164 samples, while the remaining samples either lacked the target components or suffered severe DNA degradation, resulting in failed amplification. Combined with morphological identification studies, it was found that out of the 180 samples, 141 were authentic, accounting for 78.33% of the total samples, while 31 samples showed adulteration and 8 samples lacked the target components, accounting for 21.67% of the total samples. Additionally, water testing revealed that 5 samples of Carthamus tinctorius herbal tea exhibited the phenomenon of weight adulteration. This study exposed the presence of adulteration and weight adulteration in scented herbal tea products, highlighting the need for regulatory authorities to expedite the establishment of quality standards in scented herbal tea industry. These findings provide valuable insights for the rapid development of the scented herbal tea industry.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Male ; Humans ; Prostate/pathology* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms/diagnostic imaging* ; Biopsy ; Nomograms ; Retrospective Studies

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Objective To observe the effect of excess oxygen supply for different time periods on the mitochondrial energy metabolism in alveolar epithelial type Ⅱ cells. Methods Rat RLE-6TN cells were assigned into a control group (21% O₂ for 4 h) and excess oxygen supply groups (95% O₂ for 1,2,3,and 4 h,res-pectively).The content of adenosine triphosphate (ATP),the activity of mitochondrial respiratory chain complex V,and the mitochondrial membrane potential were determined by luciferase assay,micro-assay,and fluorescent probe JC-1,respectively.Real-time fluorescence quantitative PCR was employed to determine the mRNA levels of NADH dehydrogenase subunit 1 (ND1),cytochrome b (Cytb),cytochrome C oxidase subunit I (COXI),and adenosine triphosphatase 6 (ATPase6) in the core subunits of mitochondrial respiratory chain complexes Ⅰ,Ⅲ,Ⅳ,and Ⅴ,respectively. Results Compared with the control group,excess oxygen supply for 1,2,3,and 4 h down-regulated the mRNA levels of ND1 (q=24.800,P<0.001;q=13.650,P<0.001;q=9.869,P<0.001;q=20.700,P<0.001),COXI (q=16.750,P<0.001;q=10.120,P<0.001;q=8.476,P<0.001;q=14.060,P<0.001),and ATPase6 (q=22.770,P<0.001;q=15.540,P<0.001;q=12.870,P<0.001;q=18.160,P<0.001).Moreover,excess oxygen supply for 1 h and 4 h decreased the ATPase activity (q=9.435,P<0.001;q=11.230,P<0.001) and ATP content (q=5.615,P=0.007;q=5.029,P=0.005).The excess oxygen supply for 2 h and 3 h did not cause significant changes in ATPase activity (q=0.156,P=0.914;q=3.197,P=0.116) and ATP content (q=0.859,P=0.557;q=1.273,P=0.652).There was no significant difference in mitochondrial membrane potential among the groups (F=0.303,P=0.869). Conclusion Short-term excess oxygen supply down-regulates the expression of the core subunits of mitochondrial respiratory chain complexes and reduces the activity of ATPase,leading to the energy metabolism disorder of alveolar epithelial type Ⅱ cells.
Animals ; Rats ; Energy Metabolism ; Adenosine Triphosphate ; Adenosine Triphosphatases ; RNA, Messenger ; Oxygen

This paper introduced the overview of the "eight trends" of Chinese medicinal materials(CMM) industry in 2021, analyzed the problems of CMM production, and put forward development suggestions. Specifically, "eight trends" could be summarized as follows.(1) The growing area of CMM tended to be stable, and some provinces began to release the local catalog of Dao-di herbs.(2) The protection process of new varieties accelerated, and a number of excellent varieties were bred.(3) The theory of ecological cultivation was further enriched, and the demonstration effect of ecological cultivation technology was prominent.(4) Some CMM realized complete mechanization and formed typical model cases.(5) The number of cultivation bases using the traceability platform increased, and provincial internet trading platforms were set up.(6) The construction of CMM industrial clusters accelerated, and the number of provincial-level regional brands increased rapidly.(7) Many new agricultural business entities were founded nationwide, and a variety of methods were used to drive the intensified development of CMM.(8) A number of local TCM laws were promulgated, and the management regulation of food and medicine homology substances catalogs was issued. On this basis, four suggestions for CMM production were proposed.(1) It is suggested to speed up the formulation of the national catalog of Dao-di herbs and carry out the certification of Dao-di herbs production bases.(2) Ecological planting of forest and grassland medicine should be further strengthened in terms of technical research and promotion based on the principle of ecological priority.(3) The basic work of disaster prevention should be paid more attention and technical measures for disaster mitigation should be developed.(4) The planted area of commonly used CMM should be incorporated into the national regular statistical system.
Agriculture ; Certification ; Commerce ; Industry ; China

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective: To investigate the experience of patients in the implementation of enhanced recovery after surgery (ERAS) strategy after radical gastrectomy and the factors affecting the treatment experience. Methods: A prospective cohort study was carried out. Patients who were diagnosed with gastric cancer by pathology and underwent radical gastrectomy at the Xijing Digestive Disease Hospital from December 2019 to December 2020 were consecutively enrolled. Those who received emergency surgery, residual gastric cancer surgery, preoperative neoadjuvant chemotherapy, non-curative tumor resection, intraperitoneal metastasis, or other malignant tumors were excluded. Patients' expectation and experience during implementation were investigated by questionnaires. The questionnaire included three main parts: patients' expectation for ERAS, patients' experience during the ERAS implementation, and patients' outcomes within 30 days after discharge. The items on the expectation and experience were ranked from 0 to 10 by patients, which indicated to be unsatisfied/unimportant and satisfied/important respectively. According to their attitudes towards the ERAS strategy, patients were divided into the support group and the reject group. Patients' expectation and experience of hospital stay, and the clinical outcomes within 30 days after discharge were compared between the two groups. Categorical data were reported as number with percentage and the quantitative data were reported as mean with standard deviation, or where appropriate, as the median with interquartile range (Q₁, Q₃). Categorical data were compared using the Chi-squared test or Fisher's exact test, where appropriate. For continuous data, Student's t test or Mann-Whitney U test were used. Complication was classified according to Clavien-Dindo classification. Results: Of the included 112 patients (88 males and 24 females), aged (57.8±10.0) years, 35 patients (31.3%) were in the support group and 77 (68.7%) in the reject group. Anxiety was detected in 56.2% (63/112) of the patients with score >8. The admission education during the ERAS implementation improved the patients' cognitions of the ERAS strategy [M(Q₁, Q₃) score: 8 (4, 10) vs. 2 (0, 5), Z=-7.130, P<0.001]. The expected hospital stay of patients was longer than the actual stay [7 (7, 10) days vs. 6 (6, 7) days, Z=-4.800, P<0.001]. During the ERAS implementation, patients had low score in early mobilization [3 (1, 6)] and early oral intake [5 (2.25, 8)]. Fifty-eight (51.8%) patients planned the ERAS implementation at home after discharge, while 32.1% (36/112) preferred to stay in hospital until they felt totally recovered. Compared with the reject group, the support group had shorter expected hospital stay [7 (6, 10) days vs. 10 (7, 15) days, Z=-2.607, P=0.009], and higher expected recovery-efficiency score [9 (8, 10) vs. 7(5, 9), Z=-3.078, P=0.002], lower expected less-pain score [8 (6, 10) vs. 6 (5, 9) days, Z=-1.996, P=0.046], expected faster recovery of physical strength score [8 (6, 10) vs. 6 (4, 9), Z=-2.200, P=0.028] and expected less drainage tube score [8 (8, 10) vs. 8 (5, 10), Z=-2.075, P=0.038]. Worrying about complications (49.1%) and self-recognition of not recovery (46.4%) were the major concerns when assessing the experience toward ERAS. During the follow-up, 105 patients received follow-up calls. There were 57.1% (60/105) of patients who experienced a variety of discomforts after discharge, including pain (28.6%), bloating (20.0%), nausea (12.4%), fatigue (7.6%), and fever (2.9%). Within 30 days after discharge, 6.7% (7/105) of patients developed Clavien-Dindo level I and II operation-associated complications, including poor wound healing, intestinal obstruction, intraperitoneal bleeding, and wound infection, all of which were cured by conservative treatment. There were no complications of level III or above in the whole group after surgery. Compared with the support group, more patients in the reject group reported that they had not yet achieved self-expected recovery when discharged [57.1% (44/77) vs. 22.9% (8/35), χ²=11.372, P<0.001], and expected to return to their daily lives [39.0% (30/77) vs. 8.6% (3/35), χ²=10.693, P<0.001], with statistically significant differences (all P<0.05). Only 52.4% (55/105) of patients returned home to continue rehabilitation, and the remaining patients chose to go to other hospitals to continue their hospitalization after discharge, with a median length of stay of 7 (7, 9) days. Compared with the reject group, the support group had a higher proportion of home rehabilitation [59.7% (12/33) vs. 36.4% (43/72), χ²=4.950, P=0.026], and shorter time of self-perceived postoperative full recovery [14 (10, 20) days vs. 15 (14, 20) days, Z=2.100, P=0.036], with statistically significant differences (all P<0.05). Conclusions: Although ERAS has promoted postoperative rehabilitation while ensuring surgical safety, it has not been unanimously recognized by patients. Adequate rehabilitation education, good analgesia, good physical recovery, and early removal of drainage tubes may improve the patient's experience of ERAS.
Enhanced Recovery After Surgery ; Female ; Gastrectomy ; Humans ; Length of Stay ; Male ; Pain ; Patient Outcome Assessment ; Postoperative Complications/surgery* ; Prospective Studies ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome