Rheumatoid arthritis （RA） is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Recent studies have shown that lactate metabolic reprogramming plays a key role in the pathological process of RA， and the accumulation of lactate in the synovial microenvironment triggers a cascade of immune regulatory effects. These metabolic changes create a self-sustaining cycle of inflammation and tissue damage， leading to progressively worsening disease. Therefore， lactate metabolism has been identified as a therapeutic target. Therapeutic strategies targeting lactate metabolism， such as LDHA inhibitors， targeting PKM2， MCT inhibitors， GPR81 antagonists， lactylation modification regulators， and nanosponges， have shown great potential in restoring immune balance and protecting joint integrity. This review summarizes the mechanisms of lactate metabolism in RA and its therapeutic applications， providing a theoretical basis for the development of novel metabolic intervention therapies.

ObjectiveTo reveal the compatibility rules of the core compound formula and traditional Chinese medicine （TCM） components for prevention and treatment of chronic atrophic gastritis （CAG） by Huazhuo Jiedu （turbidity-resolving and detoxifying） therapy through uniform design in view of the potential regulatory pathway of endogenous turbid-toxin retention in CAG， elucidate the potential pathway by which the compound formulas regulate the Wnt/β-catenin-connexin 43 （CX43） signaling axis， demonstrated the efficacy enhancement and toxicity attenuation among the components， thus providing experimental evidence for the scientific application of multi-component， multi-target compatibility in TCM compound formulas. MethodsA mouse model of CAG was established with N-methyl-N-nitrosourea （MNU）. Sixty mice were randomly allocated into 5 groups （n=12 per group）： blank control， model， low-dose Huazhuo Jiedu core compound formula （HXFF-L， 4.004 g·kg^-1）， high-dose Huazhuo Jiedu core compound formula （HXFF-H， 8.008 g·kg^-1）， and positive control （folic acid at 11 mg·kg^-1 + vitamin B₁₂ at 14 mg·kg^-1）. The therapeutic efficacy and molecular mechanism of the core compound formula were evaluated by hematoxylin-eosin （HE） staining， Alcian blue-periodic acid-Schiff （AB-PAS） staining， enzyme-linked immunosorbent assay （ELISA）， transmission electron microscopy （TEM）， immunofluorescence assay， and Western blot. The chemical components of the core compound formula were detected and effective components were screened by ultra-high performance liquid chromatography coupled with quadrupole-orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS）. Another 120 mice were randomized into blank control， model， and 8 HXFF component-combination groups with different dosages （uniform design groups 1-8， n=12 per group）. A uniform design was adopted， with pathological scores of mouse gastric tissue as well as serum levels of pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， and gastrin 17 （GAS17） set as dependent variables. Multivariate linear regression analysis was performed to predict the optimal proportion of core components in the compound formula and explore its compatibility rules. ResultsPharmacodynamic validation showed that compared with the blank control group， the model group had decreased gastric weight index （P<0.01） and increased pathological damage score and inflammatory factor levels （P<0.01）. Compared with the model group， these indicators were reversed in the HXFF-L， HXFF-H， and positive control groups （P<0.05， P<0.01）. Immunofluorescence results showed that CX43 expression was downregulated in the model group compared with the blank control group （P<0.01） and upregulated in the HXFF-H and positive control groups compared with the model group （P<0.05， P<0.01）. Western blot results showed that compared with the blank control group， the model group demonstrated upregulated protein levels of Wnt and β-catenin in the gastric tissue （P<0.01）. Compared with those in the model group， the protein level of Wnt was downregulated in the HXFF-L， HXFF-H， and positive control groups （P<0.05， P<0.01）， while that of β-catenin was downregulated only in the HXFF-H group （P<0.05）. A total of 25 compounds were identified in the core compound formula， including 9 from Coptidis Rhizoma， 10 from Pogostemonis Herba， 2 from Scorpio， and 4 from Lilii Bulbus. According to the category and origin of compounds， Coptidis Rhizoma alkaloids， Pogostemonis Herba volatile oils， Scorpio peptides， and Lilii Bulbus alkaloids were finally selected for component research. The predicted optimal combination of TCM components was as follows： Coptidis Rhizoma alkaloids at 75 mg·kg^-1， Pogostemonis Herba volatile oils at 2.25 mg·kg^-1， Scorpio protein extract at 90 mg·kg^-1， and Lilii Bulbus alkaloids at 9 mg·kg^-1. Coptidis Rhizoma alkaloids， Scorpio protein extract， Pogostemonis Herba volatile oils， and Lilii Bulbus alkaloids can ameliorate pathological lesions of the gastric tissue. Scorpio protein extract exerted positive regulatory effects on the gastric function， while Pogostemonis Herba volatile oils and Lilii Bulbus alkaloids showed negative correlations with partial gastric function indicators. Further investigations are required to clarify their dose-effect relationships and safety profiles. ConclusionThis study， for the first time， predicts the optimal proportion and synergistic regulatory mechanism of the core compound formula of Huazhuo Jiedu therapy， revealing the synergistic compatibility logic of its components. It provides a novel strategy for the precise TCM treatment of CAG and the modern development of compound formulas.

ObjectiveTo reveal the compatibility rules of the core compound formula and traditional Chinese medicine （TCM） components for prevention and treatment of chronic atrophic gastritis （CAG） by Huazhuo Jiedu （turbidity-resolving and detoxifying） therapy through uniform design in view of the potential regulatory pathway of endogenous turbid-toxin retention in CAG， elucidate the potential pathway by which the compound formulas regulate the Wnt/β-catenin-connexin 43 （CX43） signaling axis， demonstrated the efficacy enhancement and toxicity attenuation among the components， thus providing experimental evidence for the scientific application of multi-component， multi-target compatibility in TCM compound formulas. MethodsA mouse model of CAG was established with N-methyl-N-nitrosourea （MNU）. Sixty mice were randomly allocated into 5 groups （n=12 per group）： blank control， model， low-dose Huazhuo Jiedu core compound formula （HXFF-L， 4.004 g·kg^-1）， high-dose Huazhuo Jiedu core compound formula （HXFF-H， 8.008 g·kg^-1）， and positive control （folic acid at 11 mg·kg^-1 + vitamin B₁₂ at 14 mg·kg^-1）. The therapeutic efficacy and molecular mechanism of the core compound formula were evaluated by hematoxylin-eosin （HE） staining， Alcian blue-periodic acid-Schiff （AB-PAS） staining， enzyme-linked immunosorbent assay （ELISA）， transmission electron microscopy （TEM）， immunofluorescence assay， and Western blot. The chemical components of the core compound formula were detected and effective components were screened by ultra-high performance liquid chromatography coupled with quadrupole-orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS）. Another 120 mice were randomized into blank control， model， and 8 HXFF component-combination groups with different dosages （uniform design groups 1-8， n=12 per group）. A uniform design was adopted， with pathological scores of mouse gastric tissue as well as serum levels of pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， and gastrin 17 （GAS17） set as dependent variables. Multivariate linear regression analysis was performed to predict the optimal proportion of core components in the compound formula and explore its compatibility rules. ResultsPharmacodynamic validation showed that compared with the blank control group， the model group had decreased gastric weight index （P<0.01） and increased pathological damage score and inflammatory factor levels （P<0.01）. Compared with the model group， these indicators were reversed in the HXFF-L， HXFF-H， and positive control groups （P<0.05， P<0.01）. Immunofluorescence results showed that CX43 expression was downregulated in the model group compared with the blank control group （P<0.01） and upregulated in the HXFF-H and positive control groups compared with the model group （P<0.05， P<0.01）. Western blot results showed that compared with the blank control group， the model group demonstrated upregulated protein levels of Wnt and β-catenin in the gastric tissue （P<0.01）. Compared with those in the model group， the protein level of Wnt was downregulated in the HXFF-L， HXFF-H， and positive control groups （P<0.05， P<0.01）， while that of β-catenin was downregulated only in the HXFF-H group （P<0.05）. A total of 25 compounds were identified in the core compound formula， including 9 from Coptidis Rhizoma， 10 from Pogostemonis Herba， 2 from Scorpio， and 4 from Lilii Bulbus. According to the category and origin of compounds， Coptidis Rhizoma alkaloids， Pogostemonis Herba volatile oils， Scorpio peptides， and Lilii Bulbus alkaloids were finally selected for component research. The predicted optimal combination of TCM components was as follows： Coptidis Rhizoma alkaloids at 75 mg·kg^-1， Pogostemonis Herba volatile oils at 2.25 mg·kg^-1， Scorpio protein extract at 90 mg·kg^-1， and Lilii Bulbus alkaloids at 9 mg·kg^-1. Coptidis Rhizoma alkaloids， Scorpio protein extract， Pogostemonis Herba volatile oils， and Lilii Bulbus alkaloids can ameliorate pathological lesions of the gastric tissue. Scorpio protein extract exerted positive regulatory effects on the gastric function， while Pogostemonis Herba volatile oils and Lilii Bulbus alkaloids showed negative correlations with partial gastric function indicators. Further investigations are required to clarify their dose-effect relationships and safety profiles. ConclusionThis study， for the first time， predicts the optimal proportion and synergistic regulatory mechanism of the core compound formula of Huazhuo Jiedu therapy， revealing the synergistic compatibility logic of its components. It provides a novel strategy for the precise TCM treatment of CAG and the modern development of compound formulas.

Objective To investigate the effect of miR-486-5P on ferroptosis in H9c2 cardiomyocytes after hypoxia/reoxygenation(H/R),and to analyze its mechanism.Methods Using H9c2 cardiomyocytes as the research object,a H/R injury model was established using cobalt chloride(CoCl2)and fresh culture medium.The cells were divided into control group,H/R group,H/R+miR-486-5P mimic NC group,H/R+miR-486-5P mimic group,H/R+miR-486-5P inhibitor NC group and H/R+miR-486-5P inhibitor group.The relative expression level of miR-486-5P was detected by quantitative reverse transcription-polymerase chain reaction(qRT-PCR).The cell viability was detected by CCK-8 method.The activities or levels of lactate dehydrogen-ase(LDH),glutathione(GSH),Fe2+and malondialdehyde(MDA)were detected by colorimetric method.The levels of reactive oxygen species(ROS)and mitochondrial membrane potential(MMP)were detected by DCFH-DA fluorescent probe and JC-1 assay,respectively.Western blot was used to detect the levels of AkT/mTOR signaling pathway proteins and ferroptosis related protein solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4)and acyl-coa synthetase long chain family member 4(ACSL4).Results Compared with the control group,the level of miR-486-5P and cell viability in the H/R group de-creased significantly(P＜0.05),while LDH activity,MDA,Fe2+level,ROS level and ACSL4 protein level in-creased significantly(P＜0.05).The GSH,MMP,SLC7A11 and GPX4 levels and p-Akt/Akt and p-mTOR/mTOR ratios were significantly decreased(P＜0.05).After H/R treatment,compared with the H/R+miR-486-5P mimic NC group,the cell viability of the H/R+miR-486-5P mimic group was significantly increased(P＜0.05).The LDH activity,MDA,Fe2+level,ROS level and ACSL4 protein level were significantly de-creased(P＜0.05),while GSH,MMP,SLC7A11 and GPX4 levels and p-Akt/Akt and p-mTOR/mTOR ratios were significantly increased(P＜0.05).Compared with the H/R+miR-486-5P inhibitor NC group,the trend of the above indicators in the H/R+miR-486-5P inhibitor group was opposite.Conclusion miR-486-5P allevi-ates hypoxia/reoxygenation-induced ferroptosis in H9c2 cells by regulating Akt/mTOR signaling pathway,and thus alleviates hypoxia/reoxygenation induced cardiomyocyte injury.

[Objective]To summarize Professor CHEN Jian's clinical experience in treating pediatric upper airway cough syndrome,which is based on the"Xuanfu"theory,and to learn how to use wind-dispelling herbs.[Methods]Through clinical observation,medical case organization,literature search and integration of clinical practice experience,this paper elaborates Professor CHEN's understanding of the etiology and pathogenesis of upper airway cough syndrome and summarizes the clinical experience of treating this disease from the perspective of"opening Xuanfu with wind-dispelling herbs",in addition with relevant cases for verification.[Results]Professor CHEN considers the lurking wind in the"Xuanfu"and the upward reversal of lung Qi as the basic pathogenesis when diagnosing and treating pediatric upper airway cough syndrome.The deficiency of Zhengqi and the lack of nourishment in the"Xuanfu"are seen as the root causes of the disease.The obstruction of"Xuanfu"with phlegm,dampness and blood stasis are the pathogenic factors.The prescription is based on"Jiuke"Recipe,with wind-dispelling herbs being a continuous thread throughout.The fundamental treatment approach is using wind-dispelling herbs to treat wind disease,and to open and consolidate the"Xuanfu".The application of wind-dispelling herbs aims to expel wind,open"Xuanfu",overcome dampness and facilitate the flow of"Xuanfu",as well as support and nourish"Xuanfu".The treatment makes differentiation between the nasal and pharyngeal areas,with simultaneous treatment of the lung orifices,ensuring the smooth flow of"Xuanfu"and harmony of the viscera.A case was presented at the end of the paper to illustrate the treatment principle of dispelling wind and opening"Xuanfu",combining both attack and supplementation,leading to the unblocking of"Xuanfu",the expulsion of lurking wind,the transformation of phlegm and dampness and the self-elimination of cough,with a definite therapeutic effect.[Conclusion]Professor CHEN's approach to treating pediatric upper airway cough syndrome with"wind-dispelling herbs to open the Xuanfu"is effective,which provides insights and experience for clinical diagnosis and treatment of the disease,which has significant enlightening significance.

[Objective]To summarize Professor CHEN Jian's clinical experience in treating pediatric upper airway cough syndrome,which is based on the"Xuanfu"theory,and to learn how to use wind-dispelling herbs.[Methods]Through clinical observation,medical case organization,literature search and integration of clinical practice experience,this paper elaborates Professor CHEN's understanding of the etiology and pathogenesis of upper airway cough syndrome and summarizes the clinical experience of treating this disease from the perspective of"opening Xuanfu with wind-dispelling herbs",in addition with relevant cases for verification.[Results]Professor CHEN considers the lurking wind in the"Xuanfu"and the upward reversal of lung Qi as the basic pathogenesis when diagnosing and treating pediatric upper airway cough syndrome.The deficiency of Zhengqi and the lack of nourishment in the"Xuanfu"are seen as the root causes of the disease.The obstruction of"Xuanfu"with phlegm,dampness and blood stasis are the pathogenic factors.The prescription is based on"Jiuke"Recipe,with wind-dispelling herbs being a continuous thread throughout.The fundamental treatment approach is using wind-dispelling herbs to treat wind disease,and to open and consolidate the"Xuanfu".The application of wind-dispelling herbs aims to expel wind,open"Xuanfu",overcome dampness and facilitate the flow of"Xuanfu",as well as support and nourish"Xuanfu".The treatment makes differentiation between the nasal and pharyngeal areas,with simultaneous treatment of the lung orifices,ensuring the smooth flow of"Xuanfu"and harmony of the viscera.A case was presented at the end of the paper to illustrate the treatment principle of dispelling wind and opening"Xuanfu",combining both attack and supplementation,leading to the unblocking of"Xuanfu",the expulsion of lurking wind,the transformation of phlegm and dampness and the self-elimination of cough,with a definite therapeutic effect.[Conclusion]Professor CHEN's approach to treating pediatric upper airway cough syndrome with"wind-dispelling herbs to open the Xuanfu"is effective,which provides insights and experience for clinical diagnosis and treatment of the disease,which has significant enlightening significance.

Objective: To investigate the mobility of vaccination personnel in community health service centers in Zhejiang Province from 2012 to 2022, so as to provide reference for strengthening the construction of the vaccination team in grassroots healthcare institutions and enhancing the quality of vaccination services. Methods: From May to July 2023, one district and one county were randomly selected from each of the 11 cities in Zhejiang Province as survey sites. Two vaccination clinic of community health service centers were selected from each site for investigation. Data on the staffing and mobility of vaccination personnel were collected to analyze the composition, vacancy rate, net inflow rate, and channels for mobility among vaccination personnel. Results: In 2022, there were 192 vaccination personnel positions established across 44 vaccination clinics, with 203 staff members on duty, with 178 in-service and officially employed staff, resulting in a vacancy of 5 positions and a vacancy rate of 2.60%. There were 184 females, accounting for 90.64%. The majority were aged 20 to <41 years old, with 140 individuals representing 68.97%. There were 128 individuals with a bachelor's degree, making up 63.05%, and 110 with intermediate professional titles, accounting for 54.19%. From 2012 to 2022, a total of 102 vaccination personnel flowed in and 68 flowed out, with a net inflow rate of 20.12%. The net inflow rate of vaccination personnel in urban areas was 12.38%, which was lower than that in rural areas (32.81%, P<0.05). The flow ratio was 100.59%, with the flow ratio of vaccination personnel in urban areas being 126.67% and that in rural areas being 57.81%. Both the inflow and outflow vaccination personnel were mainly aged 20 to <31 years old (71.57% and 52.94%), with a bachelor's degree (73.53% and 61.76%), a junior professional title (70.59% and 55.88%), and no permanent position (62.75% and 61.76%). The main inflow channels for vaccination personnel was the recruitment of people, accounting for 70.57%; the main outflow channels were job transfer and resignation, accounting for 57.35% and 27.94% respectively. Conclusions From 2012 to 2022, the number of vaccination personnel in cornmunity health service centers in Zhejiang Province increased, but the personnel turnover was relatively high. Moreover, there were issues such as high personnel mobility in urban areas and instability in the ranks of young and junior professional title holders.

Objective:To develop a risk prediction model for moderate to severe orthodontic-induced inflammatory root resorption (OIIRR) of maxillary incisors based on cone beam CT (CBCT) radiomics features and clinical characteristics of the orthodontic patients.Methods:Clinical and CBCT data from 101 orthodontic patients treated by the same attending orthodontist in the Department of Orthodontics, Stomatology Hospital of Tianjin Medical University from January 2019 to January 2024 were retrospectively collected. The sample included 42 class Ⅰ patients, 52 class Ⅱ patients and 7 class Ⅲ patients [age: (19.7±6.3) years], and a total of 394 maxillary incisors were analyzed. Potential influencing factors for moderate to severe OIIRR (root volume resorption rate≥10%) were collected from the patients′ CBCT and medical records, including initial age, gender, treatment duration, Angle′s classification, extraction or not, type of orthodontic appliance (fixed or clear aligner), changes in root inclination, root movement distance and direction, pre-treatment cephalometric measurements, pre-treatment root-bone relationship, pre-treatment root length, and pre-treatment radiomics features of the teeth. Univariate analysis was initially performed to screen for factors influencing moderate to severe OIIRR. Subsequently, least absolute shrinkage and selection operator (LASSO) regression, best subset regression, and random forest were used for feature selection to construct the OIIRR risk prediction model. The discrimination, calibration, and net benefit of the three risk prediction models were evaluated, and the optimal model was displayed using a nomogram.Results:LASSO regression identified clinical features including initial age (LASSO coefficient 0.052), treatment duration (LASSO coefficient 0.024), pre-treatment root length (LASSO coefficient -0.023), and vertical root movement distance (LASSO coefficient -0.029). Initial age and treatment duration were positively correlated with the severity of OIIRR, while root length and vertical root movement distance were negatively correlated. A total of 14 radiomics features were identified, including 2 original image features and 12 wavelet features. Best subset regression identified vertical root movement distance as the clinical feature and 7 radiomics features, including 1 original image feature and 6 wavelet features. The random forest model identified 8 wavelet features as important predictors, and all of which were radiomics features. Model performance evaluation showed that the random forest model had the highest discrimination, calibration, and net benefit, making it the optimal model, with radiomics features being the most important predictors.Conclusions:Based on the data from this study, radiomics features were identified as the most important predictors by the optimal model for OIIRR risk prediction. Predicting the occurrence of moderate to severe OIIRR before orthodontic treatment held potential clinical application value.

ObjectivesTo analyze the trends in mortality and disease burden of colorectal cancer (CRC) among the registered residents in Danyang City, Jiangsu Province, from 2013 to 2023, and to provide a scientific basis for developing CRC prevention and control strategies. MethodsMortality surveillance data on CRC among the registered residents in Danyang City from 2013 to 2023 were collected and analyzed. Crude mortality rate (CMR), age-standardized mortality rate (ASMR), years of life lost (YLL) due to premature death, and YLL rate were calculated. The annual percentage change (APC) and average annual percent change (AAPC) of CMR, ASMR and YLL rate were calculated with Joinpoint Regression Program 4.9.0.1. ResultsA total of 1 920 deaths from colorectal cancer were recorded in Danyang City during 2013‒2023, with an average annual CMR of 21.75/100 000, which showed an upward trend (APC=6.47%, 95%CI: 4.21%‒8.79%, P<0.001), with higher CMR observed in males than that in females. The overall ASMR by Chinese standard population was 12.10/100 000, with no obvious temporal trends (APC=1.37%, P=0.364). ASMR increased with age, particularly after 45 years. The total YLL due to CRC was 34 711 person-years, with an average YLL rate of 3.93‰. The YLL rate showed a significant upward trend from 2013 to 2023 (APC=4.96%, 95%CI: 4.08%‒18.16%, P<0.001) in Danyang City. ConclusionThe mortality rate of colorectal cancer in Danyang City is relatively high and has shown a rising trend, resulting in an increasing disease burden on the residents year by year. Continued efforts to strengthen CRC prevention and control are needed, particularly targeting males and the elderly population.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*