Objective: To investigate the characteristics of malignant tumor incidence and mortality in cancer registration areas of Sichuan Province in 2021. Methods: Cancer registration data from 142 registries in Sichuan Province in 2021 were collected via the China Cancer Registry Platform. Crude incidence and crude mortality were calculated. The Chinese population-standardized incidence and world population-standardized incidence were standardized using the age structure of the standard population from the Fifth National Population Census in 2000 and Segi's world standard population. Descriptive analyses examined the distribution of rates by genders, urban/rural areas, and ages, and the ranking of leading cancer sites. Results: In 2021, there were 248 600 new malignant tumor cases reported in Sichuan Province, with a crude incidence of 296.37/100 000. The Chinese population-standardized incidence and world population-standardized incidence were 164.67/100 000 and 160.47/100 000, respectively. There were 158 673 malignant tumor deaths, with a crude mortality of 189.16/100 000. The Chinese population-standardized mortality and world population-standardized mortality were 92.47/100 000 and 92.00/100 000, respectively. The Chinese population-standardized incidence and mortality in males were higher than in females (179.56/100 000 vs. 151.62/100 000, 125.09/100 000 vs. 60.35/100 000). The Chinese population-standardized incidence and mortality in urban areas were higher than in rural areas (175.74/100 000 vs. 157.54/100 000, 93.63/100 000 vs. 91.82/100 000). Both the crude incidence and crude mortality increased with age. The top ten malignant tumors by crude incidence were lung cancer, colorectal cancer, liver cancer, breast cancer, esophageal cancer, gastric cancer, cervical cancer, prostate cancer, thyroid cancer, and corpus uteri cancer, accounting for 76.33% of all new cases. The top ten by crude mortality were lung cancer, liver cancer, esophageal cancer, colorectal cancer, gastric cancer, breast cancer, pancreatic cancer, cervical cancer, prostate cancer, and brain tumors, accounting for 82.39% of all cancer deaths. Conclusions In registration areas of Sichuan Province, the incidence and mortality of malignant tumors are relatively low. Key populations such as males, urban residents, and the elderly require focused prevention and control efforts. Comprehensive measures should be prioritized for malignant tumors including lung cancer, liver cancer, esophageal cancer, gastric cancer, colorectal cancer, and breast cancer.

The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl₂+I/R group), lung I/R + high-dose ZnCl₂ group (HZnCl₂+I/R group), lung I/R + medium-dose ZnCl₂ group (MZnCl₂+I/R group) and TPEN+MZnCl₂+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn²⁺ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl₂+I/R group and HZnCl₂+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn²⁺ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn²⁺ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl₂ on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl₂ can improve lung I/R injury in rats.
Animals ; Reperfusion Injury/pathology* ; Male ; Rats, Sprague-Dawley ; Rats ; Chlorides/administration & dosage* ; Lung/pathology* ; Zinc Compounds/administration & dosage* ; Apoptosis/drug effects* ; Caspase 3/metabolism* ; Cation Transport Proteins/metabolism*

The therapeutic effects of Yueju Pills on depression and cardiovascular diseases have been widely recognized. Previous studies have shown that the drug can significantly improve depressive-like behaviors induced by chronic unpredictable mild stress(CUMS) combined with atherosclerosis(AS). Given the complex pathogenesis of psychocardiac diseases, this study integrated metabolomics and network pharmacology to systematically elucidate the mechanism of Yueju Pills in alleviating depressive symptoms in psychocardiac diseases. The results demonstrate that, after Yueju Pill intervention, the levels of 9 abnormal metabolites in the hippocampus restore to normal ranges, primarily involving key pathways or signaling pathways, including the cyclic adenosine monophosphate(cAMP), mammalian target of rapamycin(mTOR), glycine/serine/threonine metabolism, and aminoacyl-tRNA biosynthesis. In a high-fat diet-induced CUMS ApoE~(-/-) mouse model, Yueju Pills significantly increases adenosine monophosphate(AMP) levels and decreases L-alanine and D-glyceric acid levels in the hippocampus. In conclusion, Yueju Pills exert antidepressant effects by regulating multiple metabolic axes, including glycine/serine/threonine metabolism and the cAMP, mTOR signaling pathways. Network pharmacology predictions reveal that the treatment of CUMS combined with AS by its core active components may be realized through modulating pathways concerning neuroinflammation and synaptic plasticity, including serine/threonine-protein kinase 1(AKT1), mitogen-activated protein kinase 1(MAPK1), and prostaglandin-endoperoxide synthase 2(PTGS2). This study provides a theoretical reference for the clinical application of Yueju Pills in alleviating the depressive symptoms of psychocardiac diseases.
Animals ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Male ; Depression/genetics* ; Humans ; Hippocampus/drug effects* ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

Objective:To observe the clinical progression of low-risk papillary thyroid microcarcinoma（LR-PTMC）, analyze the influencing factors of its oncological outcomes, and explore the feasibility of active surveillance（AS） of LR-PTMC. Methods:This study adopted a prospective observational research design. A total of 85 subjects diagnosed with LR-PTMC during health checkup in Health Management Center of our hospital from March 2021 to October 2022 were enrolled as the research subjects, for at least 2 years of AS follow-up observation. The clinical progress and oncological outcomes were recorded, disease progression was defined as any increase in nodule diameter ≥3 mm or the appearance of new lesions or lymph node metastasis or distant metastasis, and the oncological outcome was use disease progression defining. Cox proportional hazards regression model was used to analyze the influencing factors of oncological outcomes in LR-PTMC patients. Results:A total of 85 LR-PTMC patients who underwent physical examinations were included in this study. The median follow-up time was 2 years, and a total of 23 patients（27.06%） experienced disease progression. Among them, 18 patients（21.18%） had enlarged lesions（any nodule diameter increased by ≥3 mm）, and 5 patients（5.88%） had abnormal or metastatic cervical lymph nodes. The 2-year cumulative disease progression rate was 9.41%. The incidence age of LR-PTMC patients was younger, with a higher proportion of ≤45 years old. The proportion of baseline nodules with a maximum diameter greater than 5 mm is higher, and the proportion of baseline TPO Ab positivity was higher. Ultrasound showed a higher proportion of microcalcifications compared to the non progression group, and the differences were statistically significant（all P<0.05）. Multivariate Cox proportional hazards regression analysis showed that age of onset ≤45 years RR 95% CI 1.052（1.018-1.088） and ultrasound showing microcalcifications RR 95% CI 3.361（1.379-8.194） were independent risk factors affecting disease progression during AS in LR-PTMC patients（P<0.05）. Conclusion:Most LR-PTMC patients maintain stable lesion size and low lymph node metastasis rate during the AS process, with good oncological outcomes in the short term. AS can be considered as a safe and effective alternative to surgical treatment for LR-PTMC patients. But for patients with onset age ≤45 years and microcalcifications, the follow-up interval can be shortened for close observation.
Humans ; Thyroid Neoplasms/pathology* ; Disease Progression ; Prospective Studies ; Carcinoma, Papillary/pathology* ; Female ; Male ; Middle Aged ; Adult ; Watchful Waiting ; Lymphatic Metastasis ; Proportional Hazards Models ; Risk Factors

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To investigate the clinical characteristics,treatment,and prognosis of children with perianal fistulizing Crohn's disease(pfCD).Methods A retrospective analysis was conducted on the children,aged 6-17 years,who were diagnosed with Crohn's disease(CD)from April 2015 to April 2023.According to the presence or absence of perianal fistulizing lesions,they were divided into two groups:pfCD(n=60)and non-pfCD(n=82).The two groups were compared in terms of clinical characteristics,treatment,and prognosis.Results The incidence of pfCD was 42.3%(60/142).The proportion of males in the pfCD group was higher than that in the non-pfCD group.Compared with the non-pfCD group,the pfCD group had a significantly higher proportion of children with involvement of the colon and small intestine or those with upper gastrointestinal lesions(P<0.05).Compared with the non-pfCD group,the pfCD group had a significantly higher rate of use of infliximab during both induction and maintenance treatment(P<0.05).In the pfCD group,the children with complex anal fistula accounted for 62%(37/60),among whom the children receiving non-cutting suspended line drainage accounted for 62%(23/37),which was significantly higher than the proportion among the children with simple anal fistula patients(4%,1/23)(P<0.05).There were no significant differences between the two groups in mucosal healing rate and clinical remission rate at week 54 of treatment(P>0.05).The pfCD group achieved a fistula healing rate of 57%(34/60)at week 54,and the children with simple anal fistula had a significantly higher rate than those with complex anal fistula(P<0.05).Conclusions There is a high incidence rate of pfCD in children with CD,and among the children with pfCD,there is a high proportion of children with the use of biological agents.There is a high proportion of children receiving non-cutting suspended line drainage among the children with complex anal fistula.The occurrence of pfCD should be closely monitored during the follow-up in children with CD.

Alzheimer disease(AD),commonly known as senile dementia,is the most common type of dementia,resulting in progressive impairment of cognitive function,and is often accompanied by a variety of psychiatric symptoms,such as agitation.Agitated symptoms in AD patients often cause an increasing burden on caregivers,and current psychiatric medications may exacerbate adverse effects such as cognitive impairment and motor retardation in patients.Therefore,non-drug intervention is a very important adjuvant treatment option.This article reviews the clinical manifestations,possible mechanisms,drug therapy and non-drug intervention measures of agitation in order to provide reference for more effective treatment of AD.

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Objective To observe the effect of Shenqi Chongcao (SQCC) Formula on the ASS1/src/STAT3 signaling pathway in a rat model of lung fibrosis and explore its therapeutic mechanism. Methods A total of 120 male SD rats were divided equally into 5 groups, including a blank control group with saline treatment and 4 groups of rat models of idiopathic pulmonary fibrosis induced by intratracheal instillation of bleomycin. One day after modeling, the rat models were treated with daily gavage of 10 mL/kg saline, SQCC decoction (0.423 g/kg), pirfenidone (10 mL/kg), or intraperitoneal injection of arginine deiminase (ADI; 2.25 mg/kg, every 3 days) for 28 days. After the treatments, the lung tissues of the rats were collected for calculating the lung/body weight ratio, observing histopathology using HE and Masson staining, and analyzing the inflammatory cells in BALF using Giemsa staining. Serum chemokine ligand 2 (CCL2) and transforming growth factor-β1 (TGF-β1) levels were measured with ELISA. The protein expressions of src, p-srcTry529, STAT3, and p-STAT3Try705 and the mRNA expressions of ASS1, src and STAT3 in the lung tissues were detected using Western blotting and RT-qPCR. Results The neutrophil, macrophage and lymphocyte counts and serum levels of CCL2 and TGF-β1 were significantly lower in SQCC, pirfenidone and ADI treatment groups than in the model group at each time point of measurement (P<0.05). P-srcTry529 and p-STAT3Try705 protein expression levels and ASS1, src, and STAT3 mRNA in the lung tissues were also significantly lower in the 3 treatment groups than in the model group (P<0.05). Conclusion SQCC Formula can alleviate lung fibrosis in rats possibly by activating the ASS1/src/STAT3 signaling pathway in the lung tissues.

Protein phosphorylation modification is an important mechanism of physiological regulation that is closely related to protein biological functions. In particular, protein kinases are responsible for catalyzing the phosphorylation process of proteins, and phosphatases are responsible for catalyzing the dephosphorylation process of phosphorylation-modified proteins, which together mediate the achievement of dynamic and reversible phosphorylation modifications of proteins. Abnormal phosphorylation levels of proteins contribute to the development of many diseases, such as cancer, neurodegenerative diseases, and chronic diseases. Therefore, rational design of small molecules to regulate protein phosphorylation is an important approach for disease treatment. Based on the mechanism of protein phosphorylation regulation, small molecule drug design strategies can be classified into three types, protein kinase modulators, phosphatase modulators, and bifunctional molecules with proximity-mediated mechanism. This review emphasizes the above three small molecule design strategies for targeting protein phosphorylation regulation, including molecular design ideas, research progress and current challenges, and provides an outlook on small molecule modulators targeting protein phosphorylation modification.