AIM: To investigate the correlation of serum interleukin-35(IL-35), immunoglobulin 4/immunoglobulin(IgG4/IgG), thyroid stimulating immunoglobulin(TSI)levels with the activity and severity of thyroid associated ophthalmopathy(TAO).METHODS:Prospective study. A total of 148 TAO patients admitted to our hospital from January 2023 to July 2024 were selected as the observation group. They were assigned into an active group(75 cases)and an inactive group(73 cases)based on their activity level, and were assigned into a severe group(95 cases)and a mild group(53 cases)based on the severity of their condition; another 148 healthy patients who underwent physical examinations were regarded as the control group. The levels of IL-35, IgG4/IgG, and TSI in serum were compared between the two groups. The correlation between serum IL-35, IgG4/IgG, and TSI levels and TAO activity and severity of illness were analyzed. A multivariate Logistic regression was performed to analyze the influencing factors of TAO patients developing severe symptoms. ROC curve was applied to analyze the diagnostic value of serum IL-35, IgG4/IgG, and TSI levels for the development of severe TAO in patients.RESULTS: Compared with the control group, the serum IL-35 level in the observation group was significantly lower, while IgG4/IgG and TSI levels were significantly higher(all P<0.01). Compared with non-active TAO patients, active TAO patients had significantly lower serum IL-35 level and significantly higher IgG4/IgG and TSI levels(all P<0.01). Compared with the mild TAO patients, severe TAO patients had significantly lower serum IL-35 level and significantly higher disease duration, IgG4/IgG, and TSI levels(all P<0.01). The serum IL-35 level was negatively correlated with TAO activity and disease severity(r=-0.529, -0.554, both P<0.01), while serum IgG4/IgG level was positively correlated with TAO activity and disease severity(r=0.625, 0.663, both P<0.01). Serum TSI levels were positively correlated with TAO activity and disease severity(r=0.594, 0.607, both P<0.01). Multivariate Logistic regression analysis showed that serum IL-35, IgG4/IgG, and TSI levels were all factors influencing the progression of TAO patients to severe disease(all P<0.01). The areas under the curve(AUC)for diagnosing the progression of TAO patients to severe disease using serum IL-35, IgG4/IgG, and TSI levels were 0.868, 0.859, and 0.830, respectively. The combined AUC for the three markers was 0.955, significantly higher than that of each individual marker(Zthree factors combination-IL-35=2.893, Zthree factors combination-IL-35=3.510, Zthree factors combination-IL-35=4.157, P=0.004, <0.01, <0.01).CONCLUSION: Serum IL-35 level is significantly downregulated in TAO patients, while IgG4/IgG and TSI levels are significantly upregulated. The levels of IL-35, IgG4/IgG, and TSI are correlated with the activity and severity of TAO, and their combination has high diagnostic value for TAO developing into severe.

Objective To investigate the global burden of visceral leishmaniasis (VL) from 1990 to 2021 and predict the trends in the burden of VL from 2022 to 2035, so as to provide insights into global VL prevention and control. Methods The global age-standardized incidence, prevalence, mortality and disability-adjusted life years (DALYs) rates of VL and their 95% uncertainty intervals (UI) were captured from the Global Burden of Disease Study 2021 (GBD 2021) data resources. The trends in the global burden of VL were evaluated with average annual percent change (AAPC) and 95% confidence interval (CI) from 1990 to 2021, and gender-, age-, country-, geographical area- and socio-demographic index (SDI)-stratified burdens of VL were analyzed. The trends in the global burden of VL were projected with a Bayesian age-period-cohort (BAPC) model from 2022 to 2035, and the associations of age-standardized incidence, prevalence, mortality, and DALYs rates of VL with SDI levels were examined with a smoothing spline model. Results The global age-standardized incidence [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)], prevalence [AAPC = -0.06%, 95% CI: (-0.06%, -0.06%)], mortality [AAPC = -0.25%, 95% CI: (-0.25%, -0.24%)] and DALYs rates of VL [AAPC = -2.38%, 95% CI: (-2.44%, -2.33%)] all appeared a tendency towards a decline from 1990 to 2021, and the highest age-standardized incidence [2.55/10⁵, 95% UI: (1.49/10⁵, 4.07/10⁵)], prevalence [0.64/10⁵, 95% UI: (0.37/10⁵, 1.02/10⁵)], mortality [0.51/10⁵, 95% UI: (0, 1.80/10⁵)] and DALYs rates of VL [33.81/10⁵, 95% UI: (0.06/10⁵, 124.09/10⁵)] were seen in tropical Latin America in 2021. The global age-standardized incidence and prevalence of VL were both higher among men [0.57/10⁵, 95% UI: (0.45/10⁵, 0.72/10⁵); 0.14/10⁵, 95% UI: (0.11/10⁵, 0.18/10⁵)] than among women [0.27/10⁵, 95% UI: (0.21/10⁵, 0.33/10⁵); 0.06/10⁵, 95% UI: (0.05/10⁵, 0.08/10⁵)], and the highest mortality of VL was found among children under 5 years of age [0.24/10⁵, 95% UI: (0.08/10⁵, 0.66/10⁵)]. The age-standardized incidence (r = -0.483, P < 0.001), prevalence (r = -0.483, P < 0.001), mortality (r = -0.511, P < 0.001) and DALYs rates of VL (r = -0.514, P < 0.001) correlated negatively with SDI levels from 1990 to 2021. In addition, the global burden of VL was projected with the BAPC model to appear a tendency towards a decline from 2022 to 2035, and the age-standardized incidence, prevalence, mortality and DALYs rates were projected to be reduced to 0.11/10⁵, 0.03/10⁵, 0.02/10⁵ and 1.44/10⁵ in 2035, respectively. Conclusions Although the global burden of VL appeared an overall tendency towards a decline from 1990 to 2021, the burden of VL showed a tendency towards a rise in Central Asia and western sub-Saharan African areas. The age-standardized incidence and prevalence rates of VL were relatively higher among men, and the age-standardized mortality of VL was relatively higher among children under 5 years of age. The global burden of VL was projected to continue to decline from 2022 to 2035.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20％CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.

Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20％CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.