ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000，respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.

Idiopathic pulmonary fibrosis （IPF） is a chronic and fibrotic lethal interstitial lung disease with poor prognosis. It is mainly treated by organ transplantation and administration of chemical drugs， which have poor efficacy and induce side effects， failing to meet the clinical needs. Therefore， it is urgent to develop more safe and effective drugs to treat IPF. Traditional Chinese medicine （TCM） has garnered increasing attention in recent years in the treatment of IPF due to its unique advantages. Increasing studies have shown that TCM has remarkable therapeutic effects on IPF and thus demonstrate broad application prospects. Modern medical research shows that the pathogenesis of IPF can be discussed from inflammation （macrophage polarization）， oxidative stress， epithelial-mesenchymal transition （EMT）， autophagy inhibition and other related signaling pathways， while few studies systematically explain the relationship between the signaling pathways and TCM theory. According to the theory of TCM， lung collateral obstruction is the basic pathogenesis of IPF. Therefore， according to the principle of dredging and replenishing lung collaterals， IPF can be treated with the methods of reinforcing healthy qi and eliminating pathogen， replenishing qi and activating blood， and detoxifying and dredging collaterals， which demonstrate definite curative effect and can effectively relieve clinical symptoms， restore the lung function and blood oxygen partial pressure， improve the quality of life of patients， and reduce adverse reactions. Experimental studies have found that dredging and replenishing lung collaterals have significant effects on IPF inflammation （macrophage polarization）， oxidative stress， EMT， autophagy inhibition and other signaling pathways. Therefore， from the perspective of impediment， this article reviews pathogenesis of IPF， the research progress in TCM treatment of IPF， and the treatment of IPF from active components， single herbs， and compound prescriptions of TCM， with the aim of revealing the scientific connotation of the treatment of IPF from impediment and providing a new theoretical basis for enriching the TCM methods of treating IPF.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

This study explored the effects and underlying mechanism of Raf kinase inhibitory protein(RKIP)on apoptosis in mast cells sensitized by Echinococcus granulosus cyst fluid.Bone marrow-derived mast cells(BMMCs)were isolated and cultured from RKIP knockout(KO)and wild-type(WT)C57BL/6 mice.Cells were divided into control and sensitized groups.The sensitized group was incubated for 24 h in RPMI1640 medium containing 10%serum from mice infected with E.granulosus,then activated for 3 h or 6 h with E.granulosus cyst fluid.The control group was incubated for 24 h in RPMI1640 medium,and then received an equal vol-ume of PBS.Cells and supernatants were collected for analysis.Flow cytometry was used to detect the expression of CD117 and FcεRⅠα on BMMCs.The levels of β-hexosaminidase,IL-4,and TNF-α in the supernatant were quantified with ELISA.Western blot analy-sis was used to assess expression changes in RKIP,apoptosis-related proteins,and pathway proteins in BMMC before and after sensi-tization.Flow cytometry analysis revealed that after 4 weeks of induction,the CD117 and FcεRⅠα double-positivity rates on both WT and KO BMMC exceeded 90%.ELISA indicated that the E.granulosus cyst fluid resulted in significantly greater β-hexosaminidase re-lease(F=16.88,P<0.05),and levels of IL-4(F=16.51,P<0.05)and TNF-α(F=9.78,P<0.05)in the KO sensitized group than the WT sensitized group.With respect to the WT control group,the WT sensitized group showed significantly down-regulated pro-tein expression levels of RKIP(F=8.20,P<0.05)and Bcl-2(F=101.40,P<0.01)after 3 h,but significantly up-regulated levels of p-PI3K(F=8.04,P<0.05),p-Akt(F=32.52,P<0.01),p-P65(F=13.29,P<0.05),and cleaved-caspase-3(F=46.34,P<0.01).With respect to the WT sensitized group,the KO sensitized group showed significantly up-regulated protein expression of p-PI3K(F=8.45,P<0.05),p-Akt(F=8.58,P<0.05),p-P65(F=11.02,P<0.05),and Bcl-2(F=84.50,P<0.001)after 3 h,but significantly down-regulated expression of cleaved-caspase-3(F=15.66,P<0.05).In conclusion,RKIP may inhibit the PI3K/Akt/NF-κB pathway,thereby inducing apoptosis in mast cells sensitized by E.granulosus cyst fluid.This process may help ease aller-gic reactions caused by mast cells in echinococcosis,thus offering a promising new approach for preventing and treating such reactions.

Objective To investigate the effect of lifestyle on cognitive decline in rural people aged 40 years and older in Xi'an.Methods This was a prospective cohort study.People aged 40 years and older in two villages in Huyi District were selected as the study population.They completed the baseline survey from October 2014 to March 2015 as well as two follow-up visits in 2016 and 2018,respectively.A comprehensive score of lifestyle was calculated based on factors including smoking,drinking,exercise,and diet collected at the baseline.The Mini-Mental State Examination(MMSE)was used to evaluate global cognitive function at both baseline and follow-up;a≥4-point decrease in MMSE score from the baseline was defined as marked cognitive decline.Multivariable Logistic regression,propensity score correction,and propensity score matching were used to investigate the relationship between lifestyle and cognitive decline.Results A total of 1 348 participants were ultimately enrolled and 56(4.2％)of them met the criteria for marked cognitive decline(△MMSE≥4-points).Among them,386(28.6％)people had smoking history,184(13.6％)were drinkers,214(15.9％)lacked physical activity,and 400(29.7％)ate a diet high in oil and salt.Generally,304(22.6％)met the definition of the unhealthy lifestyle(comprehensive score＜6),which means more than one of the four subscales was unhealthy or more than two were relatively unhealthy.Multivariable Logistic regression analysis showed that unhealthy lifestyle was positively associated with marked cognitive decline(OR=2.838,95％CI:1.302-5.525,P=0.005).Propensity-score adjusted model yielded very similar results(OR=2.786,95％CI:1.371-5.661,P=0.005).Propensity score matching was performed to further balance the differences in covariates between the two groups.Multivariate Logistic regression analysis conducted in the matched population revealed that the risk of marked cognitive decline was still higher in those with unhealthy lifestyle(OR=3.994,95％CI:1.582-12.176,P=0.006).Conclusion Unhealthy lifestyle is associated with an increased risk of cognitive decline in cognitively normal people aged 40 years and older.

Objective:To understand the latent categories of apathy in young and middle-aged patients with hemorrhagic stroke and analyze the relationship between these categories and disability acceptance, providing a theoretical basis for targeted interventions.Methods:A convenience sampling method was used to select young and middle-aged patients with hemorrhagic stroke hospitalized at Huai′an First Hospital Affiliated to Nanjing Medical University between September 2020 and September 2023. A general information questionnaire, the Apathy Evaluation Scale-Clinician Administered, and the Acceptance of Disability Scale Revised were used for a cross-sectional survey. Latent profile analysis was conducted using Mplus 8.7 software to categorize apathy in these patients, and differences in disability acceptance among the categories were compared.Results:A total of 210 questionnaires were distributed and 203 valid questionnaires were collected. Among 203 patients were included, with 112 males and 91 females, aged 30-59 (47.60 ± 8.51) years old. The apathy score was (46.66 ± 8.78) points, and three latent categories were identified: "high active ability-low apathy" (26.1%, 53/203), "high social ability-moderate apathy" (28.6%, 58/203), and "generally high apathy" (45.3%, 92/203). The total disability acceptance scores for the three categories were (78.19 ± 13.30), (69.50 ± 11.01), and (60.86 ± 14.00) points, respectively, with statistically significant differences ( F=30.39, P<0.01). Conclusions:Apathy in young and middle-aged patients with hemorrhagic stroke can be categorized into three latent profiles, with differences in disability acceptance among the categories. Targeted management and interventions should be developed based on these homogeneous groups to improve disability acceptance.

[Purpose]To analyze the incidence and mortality of liver cancer in Fusui County of Guangxi Zhuang Autonomous Region in 2019 and the trend of change from 201 1 to 2019.[Meth-ods]Based on the incidence and mortality data of liver cancer in Fusui County from 2011 to 2019,the crude incidence rate,crude mortality rate,age-standardized rate by Chinese standard population(ASIRC/ASMRC),age-standardized rate by world standard population(ASMRW/ASM-RW),disability-adjusted life years(DALY),years of life lost(YLL),years of lived with disability(YLD)were calculated.The Joinpoint linear regression model was used to calculate the average annual percentage change(AAPC)of the ASIRC/ASMRC and DALY rate of liver cancer in Fusui County from 2011 to 2019.[Results]In 2019,there were 345 new cases and 298 deaths of liver cancer in Fusui County,accounting for 28.49％and 35.86％of all new cases and death cases of malignant tumors in Fusui County,respectively.The crude incidence rate,ASIRC and ASIRW were 74.71/105,67.55/105 and 65.63/105,respectively;the crude mortality rate,ASMRC and ASMRW were 64.53/105,58.78/105 and 56.88/105,respectively.In 2019,ASIRC/ASMRC of men were higher than those of women(105.32/105 and 95.67/105 for men;27.26/105 and 19.11/105 for women).The peak incidence and mortality rates were in the 65～69 and 80～84 age groups,re-spectively.The incidence rate of liver cancer in Fusui County declined from 82.50/105 in 2011 to 67.55/105 in 2019,with an AAPC of-3.01％(P=0.024),but the mortality rate did not have sig-nificant changes(AAPC=-1.44％,P=0.224).The rate of DALY decreased from 14.51/105 to 10.36/105,with an AAPC of-2.82％(P=0.050).[Conclusion]The incidence rate and DALY rate of liv-er cancer in Fusui County showed an overall decreasing trend from 2011 to 2019,but still re-mained at a high level.It is necessary to further strengthen the prevention,screening and early treatment of liver cancer in this region,especially for men and the elderly.

Objective:To observe the effects of acupuncture on intestinal flora and inflammatory factor interleukin(IL)-6 in ulcerative colitis(UC)model rats and to explore the related mechanism of acupuncture in treating UC.Methods:Thirty-two Sprague-Dawley rats were randomly divided into a normal control(NC)group,a model(MO)group,a mesalazine(ME)group,and an acupuncture(AC)group,with 8 rats in each group.Rats,except those in the NC group,were given a 2.5%sodium dextran sulfate solution to establish UC models.After successful modeling,rats in the ME group were treated with mesalazine by gavage twice a day for 7 continuous days;rats in the AC group received acupuncture at bilateral Tianshu(ST25)and Zusanli(ST36)with needles retained for 20 min each time,once a day for 7 consecutive days.After intervention,changes in the intestinal flora diversity,colon tissue damage degree,and inflammatory factor expression in each group of rats were evaluated.Results:The body mass increased slowly in the MO group compared to the NC group.After intervention,the body mass increased more significantly,colon injuries recovered,and intestinal flora diversity improved in the ME and AC groups compared to the MO group(P<0.05).The IL-6 expression level was higher in the MO group compared to the NC group(P<0.05).The IL-6 expression level decreased in the AC group compared to the MO group(P<0.05).Conclusion:Acupuncture at Tianshu(ST25)and Zusanli(ST36)improves body mass loss and colon injuries,regulates intestinal flora diversity,and reduces the expression of inflammatory factor IL-6 in the colon tissue of UC rats,therefore alleviating the disease severity of UC.