OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.
Biomarkers ; Carcinoma, Hepatocellular ; Golgi Apparatus ; Humans ; Liver Cirrhosis ; Liver Neoplasms

Although herbal medicines(HMs)are widely used in the prevention and treatment of obesity and obesity-associated disorders,the key constituents exhibiting anti-obesity activity and their molecular mechanisms are poorly understood.Recently,we assessed the inhibitory potentials of several HMs against human pancreatic lipase(hPL,a key therapeutic target for human obesity),among which the root-extract of Rhodiola crenulata(ERC)showed the most potent anti-hPL activity.In this study,we adopted an integrated strategy,involving bioactivity-guided fractionation techniques,chemical profiling,and biochemical assays,to identify the key anti-hPL constituents in ERC.Nine ERC fractions(retention time=12.5-35 min),obtained using reverse-phase liquid chromatography,showed strong anti-hPL activity,while the major constituents in these bioactive fractions were subsequently identified using liquid chromatography-quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS/MS).Among the identified ERC constituents,1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose(PGG)and catechin gallate(CG)showed the most potent anti-hPL activity,with pIC50 values of 7.59±0.03 and 7.68±0.23,respectively.Further investigations revealed that PGG and CG potently inhibited hPL in a non-competitive manner,with inhibition constant(Ki)values of 0.012 and 0.082 μM,respectively.Collectively,our integrative analyses enabled us to efficiently identify and characterize the key anti-obesity constituents in ERC,as well as to elucidate their anti-hPL mechanisms.These findings provide convincing evidence in support of the anti-obesity and lipid-lowering properties of ERC.

Objective:To analyze the expression pattern, mechanism and clinical significance of melanoma-associated antigen-C2 (MAGE-C2) in tumor-free breast specimens, breast benign disease specimens and breast cancer specimens.Methods:Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to investigate the expressions of MAGE-C2 in 60 tumor-free breast specimens, 60 breast benign disease specimens and 60 breast cancer specimens. The correlation of MAGE-C2 expression with clinicopathological parameters and prognosis of breast cancer patients were analyzed. The expression of MAGE-C2 was also detected by RT-PCR in breast cancer cell MCF-7 and MDA-MB-231 treated with DNA methylase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA).Results:The positive expression rates of MAGE-C2 mRNA and protein were 61.7% (37/60) and 58.3% (35/60) in breast cancer specimens, respectively, while negative expressed in breast and begin disease specimens. MAGE-C2 protein expression was associated with tumor grade, histological type and blood vessel invasion of breast cancer patients ( P<0.05). The incidence of recurrence-free survival of patients with positive MAGE-C2 expression were lower than that of patients with negative MAGE-C2 expression ( P<0.05). Multivariate Cox regression analysis showed that the clinical stage ( P<0.01), lymph node metastasis ( P<0.05) and MAGE-C2 expression ( P<0.05) were the independent prognostic factors of breast cancer patients. The MAGE-C2 mRNA was not observed in the control and TSA treated breast cancer cells while upregulated in the 5-aza-CdR treated cells. Besides, 5-aza-CdR combined with TSA further enhanced MAGE-C2 mRNA level in breast cancer cells ( P<0.05). Conclusions:MAGE-C2 is one of the tumor-specific antigen and its expression is related with the poor prognosis of breast cancer patients. DNA methylation and histone acetylation may be an important regulation mechanism of MAGE-C2 gene expression.

Objective:To analyze the expression pattern, mechanism and clinical significance of melanoma-associated antigen-C2 (MAGE-C2) in tumor-free breast specimens, breast benign disease specimens and breast cancer specimens.Methods:Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to investigate the expressions of MAGE-C2 in 60 tumor-free breast specimens, 60 breast benign disease specimens and 60 breast cancer specimens. The correlation of MAGE-C2 expression with clinicopathological parameters and prognosis of breast cancer patients were analyzed. The expression of MAGE-C2 was also detected by RT-PCR in breast cancer cell MCF-7 and MDA-MB-231 treated with DNA methylase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA).Results:The positive expression rates of MAGE-C2 mRNA and protein were 61.7% (37/60) and 58.3% (35/60) in breast cancer specimens, respectively, while negative expressed in breast and begin disease specimens. MAGE-C2 protein expression was associated with tumor grade, histological type and blood vessel invasion of breast cancer patients ( P<0.05). The incidence of recurrence-free survival of patients with positive MAGE-C2 expression were lower than that of patients with negative MAGE-C2 expression ( P<0.05). Multivariate Cox regression analysis showed that the clinical stage ( P<0.01), lymph node metastasis ( P<0.05) and MAGE-C2 expression ( P<0.05) were the independent prognostic factors of breast cancer patients. The MAGE-C2 mRNA was not observed in the control and TSA treated breast cancer cells while upregulated in the 5-aza-CdR treated cells. Besides, 5-aza-CdR combined with TSA further enhanced MAGE-C2 mRNA level in breast cancer cells ( P<0.05). Conclusions:MAGE-C2 is one of the tumor-specific antigen and its expression is related with the poor prognosis of breast cancer patients. DNA methylation and histone acetylation may be an important regulation mechanism of MAGE-C2 gene expression.

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.
Adenosine Triphosphate ; Animals ; Chemical and Drug Induced Liver Injury/etiology* ; Flavonoids ; Humans ; Inflammasomes ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nigericin

OBJECTIVE: To observe the effect of acupuncture at METHODS: Sixty patients with type-2 diabetic peripheral neuropathy were randomly divided into an observation group and a control group, 30 cases in each one. Both groups were treated with basic treatment, and the observation group was additionally treated with acupuncture at Neiting (ST 44), Xiangu (ST 43), Dadu (SP 2), Taibai (SP 3), Zusanli (ST 36), etc. once every other day, 3 times a week for 4 weeks. The changes of TCM symptom score, Toronto clinical assessment (TCSS) score, visual analogue scale (VAS) score of pain and serum tumor necrosis factor α(TNF-α) level were observed before and after treatment in the two groups, and the clinical effects of the two groups were evaluated. RESULTS: Compared before treatment, the TCM syndrome score and the TCSS score in the two groups were reduced after treatment ( CONCLUSION Acupuncture at
Acupuncture Points ; Acupuncture Therapy ; Diabetes Mellitus, Type 2/therapy* ; Diabetic Neuropathies/therapy* ; Humans ; Rivers ; Treatment Outcome

Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm² vs. 1.4(1.1-1.9)mm², all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.
Aged ; Coronary Angiography ; Humans ; Inflammation ; Male ; Middle Aged ; Myocardial Infarction/diagnostic imaging* ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic/diagnostic imaging* ; Retrospective Studies ; ST Elevation Myocardial Infarction/surgery* ; Stroke Volume ; Thrombolytic Therapy ; Ventricular Function, Left

[Abstract] Objective: To investigate the expression of MAGE-C1 (melanoma-associated antigen-C1) in breast cancer tissues and its correlation with clinicopathological features and prognosis of breast cancer patients. Methods: Breast cancer tissues, normal breast tissues and benign breast lesion tissues (60 samples for each) were collected from the Fourth Hospital of Hebei Medical University during January 2008 and December 2008.The mRNA and protein expressions of MAGE-C1 in three types of breast tissues were detected by RT-PCR and immunohistochemistry, and their correlation with clinicopathological parameters and prognosis of breast cancer patients were also analyzed. DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA) were used to treat breast cancer MDA-MB-231 and MCF-7 cells, and RT-PCR was used to determine the changes in mRNA expression of MAGE-C1 after drug treatment. Results: The positive expression rate of MAGE-C1 mRNA and protein in breast cancer tissues were 43.3% (26/60) and 38.3% (23/60), respectively; and the mRNA and protein expressions of MAGE-C1 were all negative in normal breast tissues and benign breast lesion tissues. MAGE-C1 expression was positively associated with high tumor grade (χ2 =6.233, P<0.05). Recurrence-free survival (RFS) of patients with negative MAGE-C1 expression was significantly longer than those patients with positive MAGE-C1 expression (χ 2 =4.213, P<0.05). MAGE-C1 expression (HR=3.980, P<0.05) and clinical stage (HR=3.637, P<0.05) could be used as independent prognostic factors for breast cancer patients. 5-Aza-CdR and/or TSA treatment had no significant influence on MAGE-C1 gene expression (P>0.05). Conclusion: MAGE-C1 is a tumor-specific antigen and its expression is associated with poor prognosis of breast cancer patients.

Obesity is an important cause of a panel of metabolic diseases, such as hypertension, hyperlipidemia, arteriosclerosis, type 2 diabetes and various cancers. Discovery of anti-obesity agents has always been a hot spot in the field of new drug research and development. Pancreatic lipase (PL, also named triacylglycerol acyl hydrolase), a key enzyme responsible for the hydrolysis of 50%-70% dietary fats in the gastrointestinal system, which has been recognized as a crucial target for the prevention and treatment of obesity. PL inhibitors can reduce the decomposition and absorption of dietary fat in the digestive organs by decreasing the hydrolytic activity of this key enzyme, which can alleviate the symptoms of metabolic diseases such as obesity and hyperlipidemia. Although a potent PL inhibitor (orlistat) has been marketed, it may trigger gastrointestinal side effects after long-term use. Therefore, it is necessary to develop more new PL inhibitors with strong inhibition potency and safety. In recent years, a large number of studies have found that some Chinese herbal extracts and their constituents can regulate lipid metabolism and treat obesity via inhibiting PL. In this paper, the research progress in the field pancreatic lipase inhibitors, as well as the extracts of Chinese herbs and their constituents with pancreatic lipase inhibitory effects were summarized. Meanwhile, the PL inhibition activities and inhibitory mechanisms of herbal constitutes were also summarized systematically. In addition, the authors also highlight the challenges in this field and the future research directions. All information and knowledge presented in this review will be very helpful for the medicinal chemists to find more potent PL inhibitors from herbs or to develop next generation anti-obesity drugs, as well as helpful for the prevention and treatment of obesity and other related metabolic diseases using herba medicines or related products.