It is proposed that cold pathogen plays an important promoting role in the onset and progression of hyperlipidemia. External exposure to cold， the gradual generation of internal cold， and the covert consumption of yang qi caused by modern lifestyle factors may all provide a pathological basis for the development of hyperlipidemia. Based on the pathogenic characteristics of cold， namely its tendency to damage yang， induce stagnation， and cause contraction， this paper suggests that the treatment of hyperlipidemia should focus on warming and tonifying， warming and resolving， and warming and unblocking， respectively. This provides a theoretical reference for the diagnosis and treatment of hyperlipidemia with traditional Chinese medicine.

BACKGROUND:Forskolin,a diterpenoid natural compound extracted from Coleus forskohlii,has a crucial regulatory role in skeletal muscle repair.However,the regulatory role of forskolin on myogenic differentiation of C2C12 skeletal muscle cells has not been fully explored.OBJECTIVE:To explore the effects of forskolin on the differentiation of C2C12 myoblast cell line and probe into the underlying molecular mechanisms.METHODS:C2C12 cells were treated with 0,0.1,0.25,0.5,1,5,10 and 20 μmol/L forskolin during growth,and cell proliferation was detected by cell counting kit-8 and qRT-PCR.C2C12 cells were treated with 0,0.25,0.5 and 1 μmol/L forskolin during the induction of myogenic differentiation.Immunofluorescence staining and qRT-PCR were used to detect C2C12 cells differentiation.Western blot was used to detect the expression level of myogenic differentiation-related signaling pathway proteins.RESULTS AND CONCLUSION:(1)The viability of C2C12 cells was decreased and cell proliferation was inhibited after treatment with high concentrations(＞1 μmol/L)of forskolin.(2)The qRT-PCR results showed that forskolin up-regulated the expression of Myh2,Myh4,Myomaker,but down-regulated the expression of Myh7 compared with the 0 μmol/L group,when C2C12 cells were differentiated for 4 days.Immunofluorescence staining results showed that the fusion index and myotube diameter of C2C12 cells were increased after forskolin treatment,and the number of myotubes was also increased.(3)Western blot results showed that the phosphorylated extracellular signal-regulated kinase 1/2 expression was inhibited;however,the phosphorylated protein kinase B was promoted after treatment with forskolin.The protein expression level of the myogenic differentiation transcription factor Myogenin was significantly up-regulated after treatment with forskolin.The above results demonstrate that forskolin may promote myogenic differentiation of C2C12 skeletal muscle cells through the extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathway.

Objective To systematically analyze the characteristics of the disease burden of hypertensive heart disease (HHD) in the elderly (≥60 years) globally and in China from 1990 to 2021, and to predict its future trends from 2022 to 2040, with the aim of providing data support for optimizing comprehensive prevention and control strategies for HHD. Methods Based on the Global Burden of Disease (GBD) 2021 database, the number of prevalent cases and disability-adjusted life years (DALYs) of HHD in the elderly were extracted for the world, China, and five regions categorized by sociodemographic index (SDI). Joinpoint regression was used to analyze the temporal trends of age-standardized prevalence rate and age-standardized DALYs rate of HHD in the elderly. A three-factor decomposition method was applied to evaluate the relative contributions of aging, population growth, and epidemiological changes to the variations in the elderly HHD burden. Additionally, a Bayesian age-period-cohort model was used to predict the elderly HHD burden from 2022 to 2040. Results In 2021, the number of prevalent elderly HHD cases reached 10 283 000 globally and 3 412 400 in China, representing increases of 179.20% and 159.20% respectively, compared with 1990. The DALYs of elderly HHD were 18 812 700 person-years globally and 4 731 400 person-years in China, rising by 76.08% and 29.45% respectively from 1990. Meanwhile, the growth rates of the number of prevalent cases and DALYs of elderly HHD varied across different SDI regions. From 1990 to 2021, the age-standardized prevalence rate of elderly HHD in China, as well as the age-standardized DALYs rate of elderly HHD both globally and in China, showed significant downward trends (all average annual percentage changes<0, all P<0.001). In 2021, the 70-74 years age group accounted for the highest proportion of prevalent cases and DALYs of elderly HHD, both globally and in China. Decomposition analysis revealed that population growth was the dominant factor driving the increase in the elderly HHD burden across all regions. The prediction model results indicated that the number of prevalent cases and DALYs of elderly HHD would continue to rise globally and in China from 2022 to 2040, with the growth rate of the elderly HHD burden in China between 2021 and 2040 expected to exceed the global average. Conclusion Over the past 32 years, although the age-standardized disease rates of elderly HHD have mainly shown a downward trend globally and in China, the absolute number of the disease burden has increased substantially. The projection model indicates a continued upward trajectory, with the growth rate in China higher than the global average. Therefore, there is an urgent need to implement precise prevention and control strategies to effectively mitigate the disease burden of elderly HHD.

ObjectiveTo establish an animal model of atrial fibrillation（AF） that accurately reflects the phlegm-heat and blood stasis（TRYZ） pathogenesis in traditional Chinese medicine. MethodsForty SPF-grade SD rats were randomly assigned using a random number table to the following groups：the control group， the TRYZ+AF group，the AF group and the TRYZ group， with ten rats in each group. The TRYZ+AF and TRYZ groups underwent a high-fat diet combined with intraperitoneal lipopolysaccharide（LPS） injection to simulate the pathological alterations of TRYZ syndrome. Groups TRYZ+AF and AF were induced with acetylcholine-calcium chloride（Ach-CaCl₂） via caudal vein injection to induce AF. The control group received no intervention and was maintained under normal conditions. The modeling period lasted 3 weeks. Electrocardiography was used to assess AF episodes and duration， echocardiography evaluated left atrial dimensions and cardiac function， fully automated biochemical analyzer measured the levels of total cholesterol（TC）， triglycerides（TG）， high-density lipoprotein cholesterol（HDL-C） and low-density lipoprotein cholesterol（LDL-C）， hemoreometer analyzed the whole blood viscosity， plasma viscosity， and whole blood reduced viscosity， a coagulation analyzer assessed prothrombin time（PT）， activated partial thromboplastin time（APTT）， thrombin time（TT）， and fibrinogen（FIB）， enzyme-linked immunosorbent assay（ELISA） was used to determine the levels of C-reactive protein（CRP）， interleukin（IL）-1β， IL-6， IL-17， tumour necrosis factor（TNF）-α， matrix metalloproteinase-9（MMP-9）， galectin-3（Gal-3）， Collagen Ⅰ， and α-smooth muscle actin（α-SMA）. Hematoxylin-eosin（HE） staining and Masson's trichrome staining were used to analyze pathological changes in atrial myocardium， Western blot was employed to detect MMP-9， Collagen Ⅰ and α-SMA protein expression in myocardial tissue， real-time quantitative polymerase chain reaction（Real-time PCR） evaluated fibrous factor gene expression levels. Changes in the TRYZ syndrome were assessed via body weight， tongue color［red（R）， green（G）， and blue（B）］， and rectal temperature. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was employed to detect differential metabolites between the control group and the TRYZ+AF group. ResultsFollowing three weeks of sustained modeling， compared with the control group， rats in the TRYZ+AF and the TRYZ groups exhibited reduced body weight， dry faeces， elevated rectal temperature， dark red tongue， decreased RGB values on the tongue surface， and markedly elevated TC and LDL-C levels（P<0.05， P<0.01）. The TRYZ+AF， TRYZ， and AF groups exhibited significantly decreased TT， APTT and PT， along with markedly elevated whole blood viscosity and FIB（P<0.05， P<0.01）. Rats in the TRYZ+AF and AF groups exhibited AF rhythm， markedly decreased heart rate， prolonged RR intervals， enlarged left atrium， and significantly reduced ejection fraction and shortening fraction（P<0.05， P<0.01）. Serum levels of CRP， IL-1β， IL-6， IL-17， TNF-α， MMP-9， Gal-3， Collagen Ⅰ， and α-SMA were elevated in rats from the TRYZ+AF， TRYZ， and AF groups compared to the control group， with the most pronounced increase observed in the TRYZ+AF group（P<0.05， P<0.01）. Histopathology revealed that the collagen fiber deposition in the atrial of rats in the TRYZ+AF， TRYZ and AF groups was higher than that in the control group（P<0.05， P<0.01）. Western blot and Real-time PCR results further demonstrated that the protein and mRNA expression levels of MMP-9， Collagen Ⅰ and α-SMA in the myocardial tissue of the TRYZ+AF group were higher than those in the other three groups（P<0.05， P<0.01）. Metabolomic analysis revealed 173 differentially expressed metabolites in the TRYZ+AF group and the control group， primarily enriched in pathways such as glycerophospholipid metabolism and glycolysis/gluconeogenesis. ConclusionThis study successfully establishes a rat model of AF integrated with the TRYZ syndrome， demonstrating the pathological process where the interactions of phlegm， heat and stasis jointly trigger tremor， this provides a reliable experimental tool for in-depth research into the biological basis of this disease syndrome.

BACKGROUND:Forskolin,a diterpenoid natural compound extracted from Coleus forskohlii,has a crucial regulatory role in skeletal muscle repair.However,the regulatory role of forskolin on myogenic differentiation of C2C12 skeletal muscle cells has not been fully explored.OBJECTIVE:To explore the effects of forskolin on the differentiation of C2C12 myoblast cell line and probe into the underlying molecular mechanisms.METHODS:C2C12 cells were treated with 0,0.1,0.25,0.5,1,5,10 and 20 μmol/L forskolin during growth,and cell proliferation was detected by cell counting kit-8 and qRT-PCR.C2C12 cells were treated with 0,0.25,0.5 and 1 μmol/L forskolin during the induction of myogenic differentiation.Immunofluorescence staining and qRT-PCR were used to detect C2C12 cells differentiation.Western blot was used to detect the expression level of myogenic differentiation-related signaling pathway proteins.RESULTS AND CONCLUSION:(1)The viability of C2C12 cells was decreased and cell proliferation was inhibited after treatment with high concentrations(＞1 μmol/L)of forskolin.(2)The qRT-PCR results showed that forskolin up-regulated the expression of Myh2,Myh4,Myomaker,but down-regulated the expression of Myh7 compared with the 0 μmol/L group,when C2C12 cells were differentiated for 4 days.Immunofluorescence staining results showed that the fusion index and myotube diameter of C2C12 cells were increased after forskolin treatment,and the number of myotubes was also increased.(3)Western blot results showed that the phosphorylated extracellular signal-regulated kinase 1/2 expression was inhibited;however,the phosphorylated protein kinase B was promoted after treatment with forskolin.The protein expression level of the myogenic differentiation transcription factor Myogenin was significantly up-regulated after treatment with forskolin.The above results demonstrate that forskolin may promote myogenic differentiation of C2C12 skeletal muscle cells through the extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathway.

AIM:To investigate the antiviral effica-cy and mechanism of Qingre Xiaoyanning(QRXYN)in vivo,and provide experimental basis for their prevention and treatment of influenza A virus.METHODS:We constructed a mouse model infect-ed with influenza A H3N2 virus.To evaluate the therapeutic effect of QRXYN on influenza A virus,we measured the body weight changes,pathologi-cal changes in lung tissue,hemagglutination titer,and viral load in mouse.To evaluate the possible mechanism of QRXYN's anti influenza A virus infec-tion,we used the ELISA to measure the levels of TNF-α,IL-1β,IL-4,IFN-γ,and vascular cell adhesion molecule-1(VCAM-1)in mouse bronchoalveolar Ia-vage fluid;used flow cytometry to assess the pro-portions of macrophages(F4/80),helper T lympho-cytes(CD4+T lymphocytes),and natural killer(NK)cells in lung tissue;and used Western blotting to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88),inhibitor of kappa B kinase-β(IKK-β),NF-kappa-B inhibitor al-pha(IκBα),and phospho-IKB alpha(p-IκBα)in lung tissue.RESULTS:Compared to the model group,both Oseltamivir and QRXYN can alleviate the se-verity of lung tissue lesions in mice,decrease the blood coagulation titer and viral load of mouse lung tissue(P＜0.01),lower the levels of TNF-α,IL-4,and VCAM-1 in bronchoalveolar lavage fluid(P＜0.05,P＜0.01),reduce the proportion of macro-phages(P＜0.05,P＜0.01),and increase the propor-tion of CD4+T lymphocytes and NK cells(P＜0.05,P＜0.01).Additionally,oseltamivir can reduce the ex-pression of MYD88 protein in mouse lungs(P＜0.05),while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs(P＜0.05).CONCLUSION:QRXYN have good in vivo antiviral ef-fects against the influenza A virus,and their mecha-nism may be related to the regulation of the immu-nologic function and NF-κB signal pathway.

AIM:To investigate the antiviral effica-cy and mechanism of Qingre Xiaoyanning(QRXYN)in vivo,and provide experimental basis for their prevention and treatment of influenza A virus.METHODS:We constructed a mouse model infect-ed with influenza A H3N2 virus.To evaluate the therapeutic effect of QRXYN on influenza A virus,we measured the body weight changes,pathologi-cal changes in lung tissue,hemagglutination titer,and viral load in mouse.To evaluate the possible mechanism of QRXYN's anti influenza A virus infec-tion,we used the ELISA to measure the levels of TNF-α,IL-1β,IL-4,IFN-γ,and vascular cell adhesion molecule-1(VCAM-1)in mouse bronchoalveolar Ia-vage fluid;used flow cytometry to assess the pro-portions of macrophages(F4/80),helper T lympho-cytes(CD4+T lymphocytes),and natural killer(NK)cells in lung tissue;and used Western blotting to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88),inhibitor of kappa B kinase-β(IKK-β),NF-kappa-B inhibitor al-pha(IκBα),and phospho-IKB alpha(p-IκBα)in lung tissue.RESULTS:Compared to the model group,both Oseltamivir and QRXYN can alleviate the se-verity of lung tissue lesions in mice,decrease the blood coagulation titer and viral load of mouse lung tissue(P＜0.01),lower the levels of TNF-α,IL-4,and VCAM-1 in bronchoalveolar lavage fluid(P＜0.05,P＜0.01),reduce the proportion of macro-phages(P＜0.05,P＜0.01),and increase the propor-tion of CD4+T lymphocytes and NK cells(P＜0.05,P＜0.01).Additionally,oseltamivir can reduce the ex-pression of MYD88 protein in mouse lungs(P＜0.05),while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs(P＜0.05).CONCLUSION:QRXYN have good in vivo antiviral ef-fects against the influenza A virus,and their mecha-nism may be related to the regulation of the immu-nologic function and NF-κB signal pathway.

Objective To investigate the impact of intergenerational caregiving on the brain structure and function of grandparents,and to analyze its correlation with caregiving factors.Methods Healthy adults(66 with grandchildren,24 without grandchildren)were recruited as study subjects,and clinical and MRI data were collected.Resting-state brain functional degree centrality(DC)and surface-based morphometry(SBM)methods were used to compare the differences in brain structure and function between the groups with and without grandchildren.The correlation between the differences in brain regions and △ values with grandchild's age,number,and time spent in childcare were assessed,respectively.Results Compared to the group without grandchildren,the group with grandchildren showed reduced surface area and cortical volume in the left middle temporal gyrus,as well as decreased DC values in the left medial superior frontal gyrus,bilateral orbital superior frontal gyrus,and left anterior cingulate and paracingulate gyrus(P＜0.05),respectively.In the grandchildren group,DC values and △ values in the left orbital superior frontal gyrus,left anterior cingulate and paracingulate gyrus were significantly positively correlated with time spent in childcare.Conclusion The brain structures and functions of grandparents related to empathy and motivation are changed in intergenerational caregiving,which may reveal the neuroplasticity after caring for their grandchildren.

Objective To investigate the effects of traditional laparoscopic surgery,natural orifice specimen extraction surgery(NOSES),and intersphincteric resection(ISR)on treatment outcomes and quality of life in patients with low rectal cancer.Methods A total of 152 patients with low rectal cancer who were admitted from January 2020 to June 2022,and they were divided into the traditional laparoscopic group(49 cases),the NOSES group(51 cases),and the ISR group(52 cases)according to the surgical method.The operation status,postoperative recovery status,pain,anal function recovery status,quality of life and complications were compared in the 3 groups.Results The operation time of the traditional laparoscopic group[(193.98±12.31)min]was lower than that of the NOSES group[(203.54±15.02)min]and the ISR group[(199.85±11.98)min](P＜0.05),operation time of NOSES group and ISR group was no difference(P＞0.05).The first exhaust time[(60.21±10.05)h],the first time of getting out of bed[(37.52±6.21)h],and the length of postoperative hospital stay[(12.51±1.47)d]in the traditional laparoscopic group were all higher than those in the NOSES group[(51.06±8.67)h,(30.13±4.92)h,and(11.27±)1.23)d]and ISR group[(53.19±9.24)h,(28.97±4.71)h,(11.73±1.35)d](P＜0.05),and there were no statistically significant differences in the first exhaust time,the first time to get out of bed,and the length of postoperative hospital stay between the NOSES and ISR groups(P＞0.05).There was no statistically significant difference in the Visual Analogue Scale(VAS)scores for pain at 4 hours,24 hours,and 48 hours after surgery among the three groups(P＞0.05).The VAS scores of the three groups at 24 hours after surgery were higher than those at 4 hours and 48 hours after surgery,and the difference was statistically significant(P＜0.05).The VAS scores of the three groups at 48 hours after surgery were higher than those at 4 hours after surgery,and the difference was statistically significant(P＜0.05).The NOSES group's Wexner score[(4.93±0.76)points]at 3 months after surgery and Wexner score[(3.21±0.42)points]at 6 months after surgery were lower than those of the ISR group[(6.32±0.93)points,(4.48±0.54)points]and the traditional laparoscopic group[(5.93±0.81)points,(4.01±0.53)points](P＜0.05),and the Wexner score of the 3 groups at 3 months after surgery was lower than that at 1 month after surgery(P＜0.05).The EORTC QLQ-C30 score of the NOSES group at 3 months after surgery was(74.82±4.01)points,and that at 6 months was(85.49±4.93)points,which were higher than those of the ISR group[(67.05±5.03)points and(71.64±4.21)points]and the traditional laparoscopic group[(70.42±3.92)points,(76.28±4.48)points](P＜0.05),and the EORTC QLQ-C30 scores of the traditional laparoscopic group at 3 and 6 months after surgery were higher than those of the ISR group,and the difference was statistically significant(P＜0.05).The EORTC QLQ-C30 score of the 3 groups at 6 months after surgery was higher than that before surgery and 3 months after surgery(P＜0.05),and the EORTC QLQ-C30 score of the 3 groups at 3 months after surgery was higher than that before surgery(P＜0.05).There was no significant difference in the incidence of total complications among the three groups(P＞0.05).Conclusion Compared with traditional laparoscopic surgery for low rectal cancer,the NOSES and ISR methods accelerate postoperative bowel function recovery,and the NOSES methods have advantages in anal function recovery and better and satisfactory quality of life.

Objective:To identify latent profile types of self-acceptance among newly diagnosed young and middle-aged patients with type 2 diabetes mellitus (T2DM), and to analyze the influencing factors.Methods:A convenience sampling method was used to recruit 162 patients with T2DM who visited the Department of Endocrinology at the First Affiliated Hospital of Zhengzhou University between March 2023 and August 2024. A general information questionnaire was used to collect demographic and clinical data. The Acceptance and Action Diabetes Questionnaire (AADQ), Type 2 Diabetes Stigma Assessment Scale (DSAS-2), Diabetes Knowledge Test 2 (DKT2), and e-Health Literacy Scale (eHEALS) were used to assess self-acceptance, diabetes-related stigma, diabetes knowledge, and electronic health literacy, respectively. Latent profile analysis (LPA) was performed to identify categories of self-acceptance based on AADQ scores. Logistic regression analysis was conducted to examine the influencing factors of self-acceptance profiles in young and middle-aged patients with T2DM. A total of 162 questionnaires were distributed, and 157 valid responses were collected, with an effective response rate of 96.91% (157/162) .Results:The mean AADQ score of the 157 patients was (46.64±10.34), ranging from 20 to 63, with a mean item score of (4.24±1.16). Three latent profile categories of self-acceptance were identified: the "high avoidance-low self-acceptance group" (28.66%, 45/157), the "moderate self-acceptance group" (47.13%, 74/157), and the "low avoidance-high self-acceptance group" (24.20%, 38/157). Logistic regression analysis showed that age, body mass index (BMI), diabetes-related stigma, diabetes knowledge, and electronic health literacy were significant influencing factors of self-acceptance profiles in young and middle-aged patients with T2DM ( P<0.05) . Conclusions:The level of self-acceptance in newly diagnosed young and middle-aged patients with type 2 diabetes mellitus remains suboptimal. Particular attention should be paid to patients who are younger, have a BMI below 24.0 kg/m 2, experience high levels of diabetes-related stigma, and have low levels of diabetes knowledge and electronic health literacy. Targeted education and management should be implemented based on patient characteristics.