ObjectiveTo analyze the epidemiological characteristics and trends of hand-foot-mouth disease (HFMD) in Hangzhou, so as to provide an evidence for developing effective prevention and control measures and evaluating the control effects. MethodsThe incidence data of HFMD in Hangzhou were collected from the Infectious Disease Reporting Information Management System of China Information System for Disease Control and Prevention. Descriptive epidemiology was applied to analyze the temporal, spatial and demographic distribution characteristics and etiology monitoring results of HFMD cases in Hangzhou from 2010 to 2023. Joinpoint regression model was used to analyze the trends of incidence rate of HFMD. Furthermore, circular distribution method was utilized to calculate the incidence peak of HFMD. ResultsFrom 2010 to 2023, the average annual reported incidence rate of HFMD in Hangzhou was 138.85/100 000, the proportion of severe cases was 0.04%, the mortality rate was 0.01/100 000, and the case fatality rate was 5.30/100 000. Both the total incidence rate and the incidence rate by sex showed an increasing trend. The annual reported incidence rate in males (158.72/100 000) was higher than that in females (117.61/100 000). The reported incidence rate showed a significant seasonal characteristic, with summer being the peak of epidemic. The results of surveillance samples suggested that the prevalence of HFMD in Hangzhou is characterized by the co-existence of multiple pathogens, with EV-A71 and CV-A16 being the dominant pathogens in the previous years and CV-A6 being the dominant pathogen since 2018. The proportion of EV-A71 in severe cases (77.19%) was higher than that in ordinary cases (15.37%), in addition, its proportion in ordinary cases, severe cases, and fatal cases all showed a decreasing trend. ConclusionThe incidence rate of HFMD in Hangzhou is still high, so it’s still necessary to continue to strengthen the prevention and control measures for key populations. In recent years, CV-A6 has been the main prevalent pathogen in Hangzhou. Further efforts in pathogen detection and analysis should be enhanced in the future.

Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Descriptive epidemiological methods were used to analyze the epidemiological characteristics of the local cluster of COVID-19 in the logistic park of Yuhang District in Hangzhou in March 2022. The cluster epidemic was detected by a case who actively visited the fever clinic. The epidemic lasted for 8 days, and a total of 58 cases (53 workers, 2 students, 1 farmer, 1 teacher and 1 unemployed) were found, including 40 males and 18 females. The age was (33.29±12.22) years. There cases were mainly in Yuhang District (48 cases, 82.77%) and Shangcheng District (7 cases, 12.07%) of Hangzhou. The real-time regeneration number peaked at 2.31 on March 10 th and decreased to 0.37 on March 15 th. The sequencing result of the indicated case was 100% homologous with the sequence uploaded from South Korea on March 4 th, 2022.

OBJECTIVE To explore the mechanism of Baihe Dihuang decoction in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking and animal experiment. METHODS TCMSP were used to predict the active components and targets of Baihe Dihuang decoction and disease-related targets were collected from GeneCards, OMIM and DRUGBANK databases, respectively. Target protein interactions were analyzed with STRING database and biological function and pathway were analyzed with Metascape database. Lastly relevant results were analyzed with Cytoscape 3.8.0. AutoDock vina software was used for molecular docking to analyze the binding energy of the active components and key targets of Baihe Dihuang decoction. PyMOL software were used to visualize the optimal docking results. ICR male mice were randomly divided into control group, model group, Rolipram group, low, medium and high dose group of Baihe Dihuang decoction. After 14 days of administration, the neurobehavioral scores of mice in each group were collected, and the expression of related proteins in brain tissue was detected, ELISA and Western blotting were used to detect the expression of the key protein cAMP, PKA, p-CREB and BDNF. At last, the adverse reaction of Baihe Dihuang decoction was observed by vomiting experiment. RESULTS A total of 13 active components and 39 key targets were collected from network pharmacology. The docking results showed that the first 10 core targets all performed well and their effects were closely related to PRKACA. Compared with the control group, the model group mice's recognition rate of new objects and the spontaneous alternation reaction rate were significantly reduced, the escape latency was significantly prolonged, and the target quadrant stay time, the number of crossing platforms were significantly reduced; cAMP, PKA, p-CREB and BDNF in the hippocampus of mice was significantly decreased. Baihe Dihuang decoction could reverse the behavior of AD mice and the expression of cAMP, PKA, p-CREB and BDNF. In the vomiting experiment, the anesthesia recovery time of the Rolipram group was significantly prolonged, while that of the Baihe Dihuang decoction group was not significantly affected. CONCLUSION The mechanism of Baihe Dihuang decoction in the treatment of AD may be related to its influence on cAMP-PKA and regulation of cAMP-PKA-CREB-BDNF signal pathway, and the adverse reactions are milder than those of clopramide.

Objective:To study the epidemiological and spatio-temporal distribution characteristics of hemorrhagic fever with renal syndrome (HFRS) in Hangzhou City, providing a scientific basis for prevention and control of HFRS.Methods:Data of HFRS cases reported in Hangzhou City from January 1, 2010 to December 31, 2022 were collected through the Infectious Disease Surveillance and Reporting Information System of China Disease Prevention and Control Information System. Descriptive epidemiological methods were used to analyze the prevalence and three-distribution characteristics of HFRS in Hangzhou City. Joinpoint regression was used to analyze the trend of HFRS incidence in Hangzhou City from 2010 to 2022. Global and local spatial autocorrelation were used to analyze the spatial distribution pattern of HFRS and the hotspots of incidence in Hangzhou City. And spatio-temporal scanning was used to analyze the spatio-temporal aggregation areas of HFRS in Hangzhou City.Results:From 2010 to 2022, a total of 224 HFRS cases were reported in Hangzhou City, with an average annual incidence of 0.18/100 000. The distribution of cases showed obvious seasonality, with peak incidence in spring (March to May) and autumn (September to November), accounting for 30.80% (69/224) and 26.34% (59/224), respectively. HFRS cases were reported in all districts (counties, cities) of the city, among which Xiaoshan District (66 cases, 29.46%), Chun'an County (41 cases, 18.30%) and Jiande City (25 cases, 11.16%) ranked the top three. The majority of the cases were individuals aged 31 to 60 (65.18%, 146/224), males (74.55%, 167/224), and farmers (46.43%, 104/224). Joinpoint regression analysis indicated that the overall incidence of HFRS in Hangzhou City was in downward trend from 2010 to 2022 [average annual percent change (AAPC) = - 5.01%, 95% confidence intervals ( CI): - 9.46% to - 0.34%, t = - 2.10, P = 0.036]. Global spatial autocorrelation analysis showed that there was a positive spatial correlation in the incidence of HFRS among various streets (townships) in Hangzhou City from 2011 to 2014, 2018, and 2020 (Moran's I > 0, Z > 1.96, P < 0.05). Local spatial autocorrelation analysis showed that from 2010 to 2022, the number of streets (towns) in hot areas (high-high) in Hangzhou City was 0, 2, 3, 3, 3, 3, 0, 0, 4, 0, 1, 0, and 1, respectively, and was relatively fixed in the southwest districts (counties, cities). Spatio-temporal scan analysis identified three clusters: Cluster I was from August 2011 to January 2015, centered on Fenkou Town in Chun'an County, involving 5 townships in Chun'an County; Cluster Ⅱ-1 was from August 2012 to March 2016, centered on Puyang Town in Xiaoshan District, involving 5 townships in Xiaoshan District; Cluster Ⅱ-2 was from June 2019 to June 2020, centered on Xiaya Town in Jiande City, not involving other streets (townships). Conclusions:From 2010 to 2022, the majority of HFRS cases in Hangzhou City are middle-aged male farmers. The overall trend of HFRS epidemic is decreasing, mainly concentrated in the southwest districts (counties, cities) of Hangzhou City. In the future, precise prevention and control measures should be implemented in key areas and among key populations.

【Objective】 To investigate the possibility of using voiding diary (VD) to predict desmopressin diacetate arginine vasopressin (DDAVP) and enuresis alarm (EA) in the treatment of primary monosymptomatic nocturnal enuresis (PMNE). 【Methods】 A total of 100 children (aged 6 to 14 years) with PMNE treated during Jan.2018 and Oct.2022 were involved. Bladder type was classified with two-week VD. Pseudo-randomization was performed using the Danish REDCap system to group patients into the randomized group and VD group. All patients were treated for 8 weeks. 【Results】 A total of 82 cases met the inclusive criteria. The effective rate was 82.50% (33/40) and 59.52% (25/42) in the VD and randomized groups, respectively, with significant difference (χ²=5.224, P=0.022). In the randomized group, if VD was not considered, the effective rate in the DDAVP and EA subgroups was 81.82% (18/22) and 25.00% (5/20), respectively, with significant difference (χ²=13.625, P=0.000). 【Conclusion】 VD can predict the therapeutic effects of PMNE. It is necessary to record VD for two weeks before selecting appropriate treatment methods. For patients who choose treatment without reference to VD, DDAVP shows better response than EA, but the recurrence rate after discontinuation of treatment requires further follow-up.

ObjectiveTo explore the clinical efficacy of Huanglian Jiedutang as an adjunctive treatment for acute cerebral infarction complicated with gastric motility disorder. MethodSixty patients with acute cerebral infarction complicated with gastric motility disorder with fire toxin syndrome were randomly divided into a western medicine control group （control group） and a traditional Chinese medicine （TCM） combined treatment group （observation group）， with 30 cases in each group. The control group received basic treatment for cerebral infarction and relevant western medical symptomatic treatment based on the patients' gastrointestinal symptoms. The observation group received Huanglian Jiedutang in addition to the treatment provided to the control group. The treatment course was 7 days. Neurological deficit scores and gastrointestinal dysfunction scores were assessed in both groups before treatment and on the 4^th and 7^th days of treatment. Gastrointestinal electrographic parameters， serum citrulline （CIT）， and motilin （MTL） levels were measured in both groups before treatment and on the 7^th day of treatment. Clinical efficacy was compared between the two groups. ResultCompared with the baseline in both groups， the neurological deficit scores and gastrointestinal dysfunction scores were significantly reduced on the 4th and 7^th days of treatment （P<0.05）. The reductions in these scores were more significant on the 7^th day compared with those on the 4^th day of treatment （P<0.05）. On the 4^th and 7^th days of treatment， the observation group showed a significantly greater reduction in neurological deficit scores and gastrointestinal dysfunction scores compared with the control group （P<0.05）. On the 7th day of treatment， compared with the baseline， both groups showed a significant increase in gastric antral and gastric body electric wave amplitudes as well as serum CIT and MTL levels （P<0.05）， and there were no statistically significant differences in the frequency of gastric antral and gastric body electric waves. On the 7th day of treatment， compared with the control group， the observation group had a significant increase in gastric antral and gastric body electric wave amplitudes as well as serum CIT and MTL levels （P<0.05）， and there were no statistically significant differences in the frequency of gastric antral and gastric body electric waves. After 7 days of treatment， the total effective rate in the observation group was 90.00% （27/30）， higher than 76.67% （23/30） in the control group， but the difference was not statistically significant. ConclusionAdjunctive treatment with Huanglian Jiedutang can effectively improve the symptoms of neurological function impairment and gastrointestinal dysfunction in patients with acute cerebral infarction complicated with gastric motility disorder， increase gastric antral and gastric body electric wave amplitudes， improve gastric motility disorder， and increase serum CIT and MTL levels， thereby improving the imbalanced secretion function of the gastrointestinal tract.

Objective:To evaluate the effect of methane on purinergic ion channel type 7 receptor (P2X 7R)/nod-like receptor protein 3 (NLRP3) signaling pathway during inflammatory responses in a rat model of spinal cord ischemia-reperfusion (I/R). Methods:Fifty-four clean-grade healthy male Sprague-Dawley rats, aged 3 months, weighing 350-380 g, were divided into 3 groups ( n=18 each) using a random number table method: sham operation group (group S), spinal cord I/R group (group I/R) and methane group (group M). Rats underwent sham operation in group S. Spinal cord ischemia was induced by occlusion of the thoracic aorta combined with controlled hypotension for 9 min, followed by reperfusion in anesthetized animals in group I/R.Methane-rich saline 10 mg/kg was intraperitoneally administered immediately after onset of reperfusion in group M. Motor sensory deficit index (MSDI) in hind limbs was measured at 12, 24 and 48 h of reperfusion.The L 3-5 segment of spinal cord was removed at 48 h of reperfusion for determination of the number of normal neurons (by Nissl staining), the number of activated microglia and expression of P2X 7R, NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), cysteine-requiring aspartate protease (caspase-1), interleukin-1beta (IL-1β) and IL-18 (by immunofluorescence staining) in anterior and posterior horns of spinal cord. Results:Compared with group S, the MSDI was significantly increased at 12, 24 and 48 h of reperfusion, and the number of normal neurons in anterior and posterior horns of spinal cord was decreased, the number of activated microglia was increased, and the expression of P2X 7R, NLRP3, ASC, caspase-1, IL-1β and IL-18 was up-regulated at 48 h of reperfusion in group I/R ( P<0.01). Compared with group I/R, the MSDI was significantly decreased at each time point of reperfusion, and the number of normal neurons in anterior and posterior horns of spinal cord was increased, the number of activated microglia was decreased, and the expression of P2X 7R, NLRP3, ASC, caspase-1, IL-1β and IL-18 was down-regulated at 48 h of reperfusion in group M ( P<0.05). Conclusion:The mechanism by which methane reduces inflammatory responses is related to inhibiting P2X7R/NLRP3 signaling pathway in a rat model of spinal cord I/R.

Objective:To evaluate the role of reactive oxygen species (ROS) /nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in desflurane preconditioning-induced reduction of lipopolysaccharide (LPS)-induced acute cerebral inflammation in rats.Methods:One hundred and twenty clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were divided into 4 groups ( n=30 each) using a random number table method: control group (group C), LPS-induced acute cerebral inflammation group (group L), desflurane preconditioning group (group D), and N-acetylcysteine plus desflurane preconditioning group (group ND). LPS 1 mg/kg was injected via the tail vein to establish the model of acute cerebral inflammation in L, D and ND groups.In group D, rats inhaled 8.2% desflurane for 1 h once a day for 5 consecutive days, and LPS was intravenously injected at 24 h after the end of the 5th inhalation.In group ND, ROS scavenger N-acetylcysteine 150 mg/kg was intraperitonealy injected at 30 min before each inhalation of desflurane, and the other treatments were similar to those previously described in group D. The expression of Nrf2 and kelch-like ECH-associated protein 1 (Keap1) in microglia and astrocytes in the hippocampal CA1 region was determined by immunofluorescence double staining before LPS injection (at 24 h after the last desflurane preconditioning). Morris water maze test was used to measure the escape latency, space exploration time spent in the original platform quadrant, and frequency of crossing the original platform at 6, 12 and 24 h after injecting LPS.The expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, interleukin-18 (IL-18) and interleukin-1beta (IL-1β) in microglia and astrocytes in the hippocampal CA1 region was determined by immunofluorescence double staining at 6, 12 and 24 h after injecting LPS.Nissl staining and immunofluorescence were used to count normal neurons and activated microglia and astrocytes in the hippocampus at 24 h after LPS injection. Results:Compared with group C, no significant change was found in the expression of Nrf2 and Keap1 in microglia and astrocytes before LPS injection ( P>0.05), and the escape latency was significantly prolonged, the space exploration time spent in the original platform quadrant was shortened, the frequency of crossing the original platform was decreased, the number of normal neurons was decreased, the number of activated microglia and astrocytes was increased, and the expression of NLRP3, ASC, caspase-1, IL-18 and IL-1β was up-regulated after injecting LPS in group L ( P<0.05). Compared with group L, the expression of Nrf2 was significantly up-regulated, and the expression of Keap1 was down-regulated before injecting LPS ( P<0.05), and the escape latency was shortened, the space exploration time spent in the original platform quadrant was prolonged, the frequency of crossing the original platform was increased, the number of normal neurons was increased, the number of activated microglia and astrocytes was reduced, and the expression of NLRP3, ASC, caspase-1, IL-18 and IL-1β was down-regulated after injecting LPS in group D( P<0.05). Compared with group D, the expression of Nrf2 was significantly down-regulated, the expression of Keap1 was up-regulated before injecting LPS ( P<0.05), and the escape latency was significantly prolonged, the space exploration time spent in the original platform quadrant was shortened, the frequency of crossing the original platform was decreased, the expression of NLRP3, ASC, caspase-1, IL-18 and IL-1β was up-regulated, the number of normal neurons was reduced, and the number of activated microglia and astrocytes was increased after LPS injection in group ND ( P<0.05). Conclusion:ROS/Nrf2 signaling pathway is involved in desflurane preconditioning-induced reduction of LPS-induced acute cerebral inflammation in rats.

Objective:To understand the characteristics and differences of diarrhea-related symptoms caused by different pathogens, and the clinical features of various pathogens causing diarrhea.Methods:Etiology surveillance program was conducted among 20 provinces of China from 2010 to 2016. The acute diarrhea outpatients were collected from clinics or hospitals. A questionnaire was used to survey demographics and clinical features. VFeces samples were taken for laboratory detection of 22 common diarrhea pathogens, to detect and analyze the clinical symptom pattern characteristics of the patient’s.Results:A total of 38 950 outpatients were enrolled from 20 provinces of China. The positive rates of Rotavirus and Norovirus were the highest among the five diarrhea-causing viruses (Rotavirus: 18.29%, Norovirus: 13.06%). In the isolation and culture of 17 diarrhea-causing bacterial, Escherichia coli showed the highest positive rates (6.25%). The clinical features of bacterial diarrhea and viral diarrhea were mainly reflected in the results of fecal traits and routine examination, but pathogenic Vibrio infection was similar to viral diarrhea. Conclusion:Infectious diarrhea presents different characteristics due to various symptoms which can provide a basis for clinical diagnosis.