BACKGROUND:Traditional Chinese medicine has rich experience and unique advantages in the empirical treatment of phlegm-heat and Fu-organs excess syndrome of ischemic stroke.In order to further explore the therapeutic targets and mechanisms of traditional Chinese medicine for this disease,it is crucial to establish a stable and reliable animal model of phlegm-heat and Fu-organs excess syndrome combined with empirical symptoms of ischemic stroke. OBJECTIVE:To explore the establishment method and evaluation system of the rat model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome. METHODS:Sixty male Sprague-Dawley rats were randomly divided into four groups:blank control group(n=12),ischemic stroke group(n=18),disease+syndrome group(n=18),phlegm-heat and Fu-organ excess syndrome group(n=12),all of which were given high-fat diet for 25 days.On the 26th day,the rats in the blank control group and ischemic stroke group were intragastrically given normal saline and high fat diet,while those in the other two groups were intragastrically given autologous feces suspension and high fat diet for 3 continuous days.After gavage,ischemic stroke models were established using the suture method in the ischemic stroke group and disease+syndrome group.The changes in diet,water intake,body mass,body temperature,fecal traits,nasal secretions,sputum in the throat,and tongue image were recorded.Neurological deficits,tongue image,blood lipid levels,morphological changes of brain tissue and carotid artery,and the serum levels of motilin and somatostatin were detected. RESULTS AND CONCLUSION:Compared with the control group,the rats in the disease+syndrome group had shortness of breath,listlessness,irritability,bradykinesia,a large number of secretions around the nose,audible and heavy sputum in the throat,decreased diet and water intake,increased body mass,body temperature,and slingual vein score,decreased fecal pellet count,Bristol score and fecal moisture content,increased serum total cholesterol,triglyceride,low-density lipoprotein and somatostatin levels,decreased motilin level,increased neurological deficit score,significant pathological changes of the carotid artery,and significant morphological changes of the brain tissue.The ischemic stroke group only showed pathological changes of ischemic brain tissue,without the characteristics of phlegm-heat and Fu-organ excess syndrome.The phlegm-heat and Fu-organ excess syndrome group could present with the typical characteristics of traditional Chinese medicine syndromes,without the pathological changes of brain tissue with ischemic stroke.To conclude,the compound modeling method of high-fat induction combined with suture method and autologous feces gavage can establish an animal model of ischemic stroke with phlegm-heat and Fu-organ excess syndrome.

ObjectiveTo analyze the incidence rate and mortality of acute myocardial infarction (AMI) and their changing trends among the registered residents in Xiaoshan District, Hangzhou City from 2017 to 2023, so as to provide references for formulating policies related to AMI prevention. MethodsThe morbidity and mortality data of AMI among the registered residents in Xiaoshan District from 2017 to 2023 were collected through the Hangzhou Chronic Disease and Death Cause Monitoring System. Software such as Excel 2019, SPSS 25.0 and Joinpoint 4.9.1.0 were used to calculate the incidence rate, mortality, and average annual percentage change (AAPC) of AMI. ResultsFrom 2017 to 2023, the average annual crude incidence rate, age-standardized incidence rate using China standard population (ASIRC), and the age-standardized incidence rate using World standard population (ASIRW) of AMI in Xiaoshan District were 48.25/100 000, 29.14/100 000, and 21.64/100 000, respectively, and, from which the AAPCs were 5.495%, 6.010%, and 6.533%, respectively, all showing an upward trend. The average annual crude mortality rate, the age-standardized mortality rate using China standard population (ASMRC), and the age-standardized mortality rate using World standard population (ASMRW) were 11.76/100 000, 6.52/100 000, and 4.71/100 000, respectively, from which the AAPCs were -9.669%, -10.433% and -9.615%, respectively, all showing a downward trend. The average annual crude incidence rate of AMI was higher in males (65.87/100 000) than that in females (31.31/100 000). Moreover, the average annual crude mortality rate of AMI was higher in males (14.08/100 000) than that in females (9.52/100 000), and the difference was statistically significant (all P<0.001) .After age grouping, the crude incidence rate of AMI among the residents aged 35-, 45-, 55-, and 65- years in Xiaoshan District from 2017 to 2023 showed an upward trend over time, with AAPCs of 16.993%, 17.149%, 8.523%, and 5.002%, respectively. While the crude mortality rate in residents aged 35-, 75-, and 85-102 years showed an decreasing trend over time, with AAPCs of -23.977%, -15.467%, and -17.415%, respectively, but there was no statistically significant difference in the trends in incidence rate and mortality of other age groups (all P>0.05). ConclusionThe situation of AMI prevention and control among the registered residents in Xiaoshan District is not optimistic, and targeted measures should be strengthened for the male residents aged ≥35 years old.

Objective: To analyze the incidence trend of colorectal cancer in Xiaoshan District, Hangzhou City from 2010 to 2024, and predict the incidence of colorectal cancer from 2025 to 2027, so as to provide the evidence for improving the prevention and control strategies of colorectal cancer. Methods: Colorectal cancer incidence data from 2010 to 2024 in Xiaoshan District were collected through the Hangzhou Municipal Chronic Disease Monitoring Management System. The crude incidence of colorectal cancer was calculated, and standardized using the data from the Sixth National Population Census in 2010 (Chinese standardized rate) and the Segi's world standard population (world standardized rate). The trend of colorectal cancer incidence from 2010 to 2024 was analyzed using the average annual percent change (AAPC). An exponential smoothing state space model with trigonometric seasonality, box-cox transformation, ARMA errors, trend and seasonal components (TBATS) was established to forecast the crude incidence of colorectal cancer from 2025 to 2027. Results: There were 10 726 new cases of colorectal cancer in Xiaoshan District from 2010 to 2024. The crude incidence, Chinese standardized rate, and world standardized rate of colorectal cancer were 59.25/100 000, 38.62/100 000 and 29.50/100 000, respectively. The crude incidence, Chinese standardized rate, and world standardized rate of colorectal cancer in males were 70.56/100 000, 44.44/100 000and 35.58/100 000, respectively, while those in females were 48.37/100 000, 32.69/100 000 and 23.70/100 000, respectively. The Chinese standardized rate of colorectal cancer was significantly higher in males than in females (P<0.05). The crude incidence of colorectal cancer in males, females and the whole population showed upward trends from 2010 to 2024 (AAPC=4.916%, 3.795% and 4.442%, all P<0.05). The crude incidence of colorectal cancer in the groups of 0-<35, 35-<50, 50-<75 and ≥75 years were 1.75/100 000, 19.86/100 000, 112.28/100 000 and 272.99/100 000, respectively, showing an increasing trend with age (P<0.05). From 2010 to 2024, the crude incidence of colorectal cancer in the ≥75 years group showed an increasing trend (AAPC=4.470%, P<0.05), while no significant trend was observed in other age groups (all P>0.05). TBATS model demonstrated good fitting (predictive) performance, indicating a year-by-year increase in the crude incidence of colorectal cancer across the whole population from 2025 to 2027, with an estimated rate reaching 70.45/100 000 in 2027. Conclusions The crude incidence of colorectal cancer in Xiaoshan District showed an increasing trend from 2010 to 2024, and it is predicted to continue to increase from 2025 to 2027. Males and the elderly are the key populations for colorectal cancer prevention and control.

OBJECTIVE: To explore the peripheral neural mechanism underlying representation along the distribution of stomach meridian induced by intestinal inflammatory reaction using diarrhea predominant-irritable bowel syndrome (IBS-D) mice. METHODS: Among 62 healthy male C57BL/6 mice of clean grade, 12 mice were randomly selected and divided into a control group and a model group, 6 mice in each group, additionally, 12 mice were randomly selected and divided into a Tianshu group, a Liangqiu group and a Zusanli group, 4 mice in each group. In the model group, citrobacter was administered orally to establish IBS-D model. In the control group and the model group, the visceral pain threshold was observed using fecal colorectal distension (fCRD) induced electromyography of external oblique muscle, the positive cell number of neutrophil in the colonic muscularis was detected by myeloperoxidase (MPO) staining, the number, location and distribution rule of Evans blue (EB) extravasation points were observed by injection of EB staining solution into the tail vein. In the Tianshu group, the Liangqiu group and the Zusanli group, fluorescent dye Dil was injected at bilateral "Tianshu" (ST25), "Liangqiu" (ST34) and "Zusanli" (ST36) respectively, to observe the dye-positive cell number in different dorsal root ganglion (DRG) segments. In the control group and the model group, the activation of satellite glial cells (SGCs) in different DRG segments was observed by immunofluorescence. RESULTS: Compared with the control group, in the model group, the area under curve of electromyography of external oblique muscle was increased at fCRD of 25, 50 and 75 μL distilled water (P<0.001, P<0.01); the MPO-positive cell number of neutrophil in the colonic muscularis was increased (P<0.01). Few EB extravasation points could be found in the control group, while there were much more EB extravasation points observed in the model group, which was specially distribution in the area of stomach meridian, from "Huaroumen" (ST24) to "Zusanli" (ST36), as well as the surface area dominated by L₂-L₅ segment of the spinal cord. The Dil-positive cells were mainly exhibited in the DRG of T₁₁, L₅ and L₄ segments in the Tianshu group, the Liangqiu group and the Zusanli group, respectively. Compared with the control group, the ratio of glial fibrillary acidic protein (GFAP)/glutamine synthetase (GS) co-expression was increased in the DRG of T₁₁, L₄ and L₅ segments in the model group (P<0.05, P<0.01). CONCLUSION The activation of SGCs within DRG of T₁₁, L₄ and L₅ segments may relate closely to the occurrence of the representation along the stomach meridian distribution in IBS-D mice.
Animals ; Male ; Mice ; Irritable Bowel Syndrome/therapy* ; Mice, Inbred C57BL ; Meridians ; Stomach/physiopathology* ; Humans ; Acupuncture Points ; Disease Models, Animal

Objective: To understand the survival status and influencing factors of first-ever stroke patients, so as to provide evidence for improving the quality of life and prognosis of stroke patients. Methods: Demographic information, medical history, smoking history, and alcohol consumption history of newly diagnosed stroke cases first reported in 2017 in Xiaoshan District were collected through the Hangzhou Chronic Disease Surveillance and Management System. Patients were followed up for 5 years, with stroke death as the outcome event. The survival rate was calculated using the Kaplan-Meier method, and factors affecting survival time of first-ever stroke patients were identified using a multivariable Cox proportional hazard regression model. Results: A total of 3 886 patients first-ever stroke patients were included, the cases of cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, and stroke unspecified as to whether it was hemorrhagic or ischemic (unspecified) accounted for 86.93%, 11.45%, 1.06% and 0.57%, respectively. There were 2 047 males (52.68%) and 1 839 females (47.32%), with a mean onset age of (72.01±11.61) years. By the end of the follow-up on December 31, 2022, 906 patients died from stroke, with a median follow-up time of 62.00 (interquartile range, 35.00) months. The 1-year survival rate was 87.35% (95%CI: 86.30%-88.41%), the 3-year survival rate was 82.11% (95%CI: 80.88%-83.34%), and the 5-year survival rate was 76.64% (95%CI: 75.26%-78.02%), respectively. Multivariable Cox proportional hazard regression analysis showed that onset age of ≥75 years (HR=5.543, 95%CI: 3.822-8.039), being treated at township-level hospitals (HR=5.934, 95%CI: 4.027-8.743), history of hypertension (HR=1.566, 95%CI: 1.317-1.863), history of chronic ischemic heart disease (HR=1.611, 95%CI: 1.362-1.906), smoking history (HR=1.455, 95%CI: 1.190-1.778), alcohol consumption history (HR=1.323, 95%CI: 1.067-1.641), stroke subtype of intracerebral hemorrhage (HR=3.442, 95%CI: 2.923-4.053) and unspecified (HR=6.843, 95%CI: 4.353-10.756) were associated with higher mortality risk among first-ever stroke patients. Conclusion The 5-year survival rate of first-ever stroke patients was 76.64%, which was influenced by age of onset, hospital level for diagnosis and treatment, stroke subtype, medical history, smoking and alcohol consumption.

Objective This study investigated the protective effects of Corni Fructus ethanol extract on β-amyloid protein 25-35 (Aβ25-35)-induced Alzheimer's disease (AD) mice by regulating histone lysine-specific demethylase 1 (LSD1) / postsynaptic density protein 95 (PSD95) on synapses and neuroinflammation. Methods Specifically, according to the body weight, 40 C57BL/6N mice were randomized into four groups: the sham operation group, the model group, the low-dose (0.1mg/g) and the high-dose (0.3 mg/g) Corni Fructus ethanol extract groups. Aβ25-35 was injected into the hippocampus of mice in three groups except for the sham operation group to established AD model. All mice were orally administered with either Corni Fructus ethanol extract or vehicle by gavage for 7 days before molding and continued 5 days after surgery for a total of 60 days. Morris water maze, Y maze and open field tests were performed to evaluate the recognition memory and space exploration ability of mice. The expression of LSD1, PSD95, synaptophysin (SYN), interleukin-1β (IL-1β), tumor necrosis factor-α(TNF-α) and H3K9me2 level were measured by Western blotting. Chromatin immunoprecipitation (CHIP) combined with qPCR was used to detect H3K9me2 modification of PSD95 promoter region and mRNA levels of PSD95. The correlation between the expression of H3K9me2 and PSD95 and the expression of IBA1 in the hippocampus were detected by immunofluorescence assay.Results The result showed that Corni Fructus ethanol extract significantly reversed Aβ25-35-induced learning and memory impairment in AD mice. Compared with the model group, Corni Fructus ethanol extract demonstrated shorter escape latency, increased number and time of autonomous activities and the rate of autonomous alternation. Moreover, it increased the expression of LSD1 in hippocampus of AD mice(P<0.05), and reduced H3K9me2 modification level in the promoter region of PSD95 gene, and then promoted the mRNA transcription and protein expression of PSD95. Immunofluorescence staining indicated the reduction of H3K9me2 modification level in hippocampus was accompanied by the enhancement of PSD95 expression. Corni Fructus ethanol extract could also inhibit the activation of microglia and reduce the expression of proinflammatory factors IL-1β and TNF-α.Conclusion Corni Fructus ethanol extract may regulate PSD95 gene transcription by up-regulating the expression of LSD1 and reducing the H3K9me2 modification level in its promoter region, thereby increasing the expression of PSD95, a key protein in synaptic plasticity regulation, which alleviate neuroinflammatory response, improve learning and memory dysfunction in AD model mice, and thus play a protective role in Aβ25-35-induced nerve damage.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Objective: To investigate the hygienic status of the central air conditioner ventilation system in public places in urban areas of Ma'anshan City, Anhui Province, so as to provide insights into formulation of supervision and management interventions. Methods: A total of 15 public places with the central air conditioner ventilation system were randomly sampled from main urban areas in Ma'anshan City in 2022. Sampling and detection were performed following the standard GB/T 18204.5—2013 Examination methods for public places Part 5: Central air conditioning ventilation system, including total number of bacteria and total number of fungus on the inner surface of wind pipes, total number of bacteria and fungus, particulate matter (PM10) and β-hemolytic streptococci in the air supply system, and Legionella pneumophila in the cooling water, and the detection indicators were assessed following the WS 394—2012 Guideline for hygiene of the central air conditioner ventilation system in public places. The eligible rate of samples, the detection rate of L. pneumophila were analyzed. Results: A total of 368 samples were collected from 15 public places, and the qualified rate was 50.54%, no places had all eligible measurement indicators. The qualified rates of total bacteria and fungus numbers on the inner surface of wind pipes were 52.67% and 59.33%. The qualified rates of total bacterium number, total fungus number, PM10 and β-hemolytic streptococci were 12.00%, 28.00%, 90.00% and 96.00% in the air supply system. The qualified rates of samples in administrative workplaces, hotels, bathing places and malls (supermarkets) were 32.50%, 59.24%, 61.09% and 68.92%, the qualified rates of total bacteria on the inner surface of air ducts were 8.33%, 72.46%, 66.67% and 61.90%, and the qualified rates of total fungus numbers in air supply were 0, 21.70%, 33.30% and 71.40%, respectively, with statistical significance (P<0.05). A total of 18 cooling water samples were collected, and L. pneumophila was detected in three samples (16.67%). Conclusions Poor hygiene is seen in the central air conditioning ventilation systems in public places in main urban areas of Ma'anshan City. High attention needs to be paid to contamination of bacterium, fungus and L. pneumophila, and expansion of supervision coverage and improved supervision intensity are recommended.

Objective: To investigate the trend in mortality of malignant tumors in Xiaoshan District, Hangzhou City from 2017 to 2022, so as to provide insights into formulation of the malignant tumor control strategy. Methods: Data on mortality of malignant tumors in Xiaoshan District from 2017 to 2022 were collected through Hangzhou Municipal Chronic Disease Monitoring Management System, and the cause of death composition ratio and crude mortality were calculated. The mortality of malignant tumors was standardized by the population of the sixth National Population Census in China in 2010. The trend in mortality of malignant tumors were evaluated with average annual percent change (AAPC). Results: There were 13 301 malignant tumor deaths reported in Xiaoshan District from 2017 to 2022, accounting for 31.26% of the total cause of death and ranking the first among the causes of death. The crude mortality was 186.36/105 and standardized mortality was 106.63/105. There was no significant trend in the crude mortality of malignant tumors in Xiaoshan District from 2017 to 2022 (P>0.05), while the standardized mortality showed a tendency towards a decline (AAPC=-1.409%, P<0.05). The crude and standardized mortality of malignant tumors were higher in men than in women (241.40/105 vs. 133.37/105; 132.66/105 vs. 79.35/105; both P<0.05). There was no obvious trend in the crude mortality of malignant tumors in men (P>0.05), and the standardized mortality showed a tendency towards a decline (AAPC=-3.017%, P<0.05). While there was no obvious trend in the crude and standardized mortality of malignant tumors in women (P>0.05). The crude mortality of malignant tumors showed a tendency towards a decline among residents at ages of 15 to 44 years and 65 years and older (AAPC=-3.933% and -2.413%, both P<0.05). The crude mortality of malignant tumors was higher in men than in women among residents at ages of 0 to 14 years, 45 to 64 years and 65 years and older (all P<0.05). The five most common causes of death included lung cancer, colorectal cancer, liver cancer, gastric cancer and pancreatic cancer, accounting for 66.96% of all malignant tumors. The crude mortality of colorectal cancer from 2017 to 2022 showed a tendency towards a rise (AAPC=2.815%, P<0.05). Conclusions The standardized mortality of malignant tumors showed a tendency towards a decline in Xiaoshan District from 2017 to 2022. Management of malignant tumors should be given a high priority among men at ages of 45 years and older, and lung cancer, colorectal cancer, liver cancer, gastric cancer and pancreatic cancer were leading causes of death.

Objective: To investigate the mortality, probability of premature death and trends due to malignant tumors, cardio-cerebrovascular diseases, diabetes and chronic respiratory diseases in Xiaoshan District, Hangzhou City from 2015 to 2021, so as to provide the basis for the formulation of chronic diseases prevention and control strategies. Methods: The deaths of the four diseases in Xiaoshan District from 2015 to 2021 were collected from Zhejiang Provincial Chronic Diseases Surveillance Information Management System. The crude mortality, standardized mortality and probability of premature death were calculated. The trends in mortality and probability of premature death were analyzed using average annual percent change (AAPC), and the attainment of probability of premature death due to the four diseases was evaluated using the targets of probability of premature death control in 2025 and 2030. Results: Totally 36 130 deaths due to the four diseases were reported in Xiaoshan District from 2015 to 2021. The crude mortality and standardized mortality were 445.20/105 and 237.81/105, which appeared a tendency towards a decline (AAPC=-1.427% and -4.051%, both P<0.05), and the probability of premature death decreased from 9.99% to 7.82%, (AAPC=-4.123%, P<0.05). The standardized mortality of malignant tumors, cardio-cerebrovascular diseases and chronic respiratory diseases appeared a tendency towards a decline (AAPC=-3.017%, -4.999%, and -6.024%, all P<0.05), while there was no significant trend in the standardized mortality of diabetes (AAPC=-0.847%, P>0.05). The probability of premature death due to malignant tumors appeared a tendency towards a decline (AAPC=-4.167%, P<0.05), while there was no significant trends seen in the probability of premature death due to diabetes, cardio-cerebrovascular diseases and chronic respiratory diseases (AAPC=0.638%, -5.250% and -2.022%, all P>0.05). The average probability of premature death due to the four diseases decreased by 4.00% each year, and decreased by 6.64% in 2025 and 5.42% in 2030 as predicted, which were both lower than the target values of 7.99% and 6.99%. Conclusions The mortality and probability of premature death due to the four diseases appeared a tendency towards a decline in Xiaoshan District from 2015 to 2021, with the probability of premature death of malignant tumors decreased significantly. It is predicted that the probability of premature death of the four diseases can reach the target in 2025 and 2030.