Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

OBJECTIVES: To investigate the impact of high expression of transmembrane and coiled helix structural domain 1 (TMCO1) on prognosis of gastric cancer and the possible mechanisms. METHODS: TMCO1 expression in gastric cancer and its effect on gastric cancer progression and prognosis were analyzed using publicly available databases and clinical data of patients undergoing radical surgery in our hospital, and its possible biological functions were explored using KEGG and GO analyses. In gastric cancer HGC-27 cells, the effects of lentivirus-mediated TMCO1 overexpression and TMCO1 silencing on cell apoptosis, proliferation, invasion and migration were examined. RESULTS: TMCO1 expression was significantly elevated in gastric cancer tissues (P<0.05), and its high expression was positively correlated with cancer progression (P<0.001) and a lowered postoperative 5-year survival rate of the patients (P<0.05). Bioinformatic analyses suggested that TMCO1 may affect gastric cancer cell apoptosis via Wnt signaling. In HGC-27 cells, TMCO1 overexpression significantly promoted tumor cell proliferation, inhibited cell apoptosis, and enhanced cell migration and invasion, whereas TMCO1 silencing produced the opposite effects. Western blotting showed that β-catenin levels were significantly upregulated in TMCO1-overexpressing cells and downregulated in cells with TMCO1 silencing. CONCLUSIONS TMCO1 is overexpressed in gastric cancer tissues, and its high expression promotes gastric cancer progression and affects long-term prognosis of the patients possibly by activating the Wnt/ β-catenin signaling pathway to inhibit apoptosis of gastric cancer cells.
Humans ; Stomach Neoplasms/metabolism* ; Apoptosis ; Prognosis ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Wnt Signaling Pathway ; beta Catenin/metabolism* ; Gene Expression Regulation, Neoplastic

Objective:Explore the predictive value of the C-reactive protein to albumin ratio (CAR) and combined indicators for the prognosis of cardiac arrest (CA) patients.Methods:Retrospective analysis was conducted on patients who recovered spontaneous circulation after cardiopulmonary resuscitation (CPR) admitted to the First Affiliated Hospital of Zhengzhou University from January 2021 to May 2023. Patients were divided into survival and non-survival groups based on their status at discharge. Baseline characteristics, CPR data, and laboratory indicators were compared between the two groups. Statistically significant indicators were further analyzed using multivariate logistic regression to identify independent risk factors affecting the prognosis of CA patients. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of each independent factor and combined indicators for the prognosis of CA patients.Results:A total of 145 patients were included in the study, including 33 patients in the survival group and 112 patients in the non-survival group. There were statistically significant differences between the survival group and the non-survival group in terms of CPR duration, the dosage of vasopressor drugs used, ICU length of stay, Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score at ICU admission, lactate, fibrinogen, aspartate aminotransferase, albumin, procalcitonin, C-reactive protein, CAR, myoglobin, and creatine kinase isoenzyme (all P < 0.05). Multivariate logistic regression analysis revealed that CAR and CPR duration were independent risk factors affecting the prognosis of CA patients (CAR: OR=2.372, 95% CI: 1.094~5.146, P=0.029; CPR duration: OR=1.170, 95% CI: 1.020~1.342, P=0.025). ROC curve analysis showed that the areas under the curve for CAR, CPR duration, and their combination in predicting patient prognosis were 0.792, 0.731, and 0.859, respectively. The cut-off values for CAR and CPR duration were 1.455 and 11.5 minutes, respectively. Conclusions:The CAR and CPR duration are independent risk factors affecting the prognosis of CA patients, and the predictive value is higher when both CAR and CPR duration are combined. A CAR greater than 1.455 and a CPR duration longer than 11.5 minutes suggest a poorer prognosis for the patients.

Objective:To study the epidemic characteristics and spatio-temporal distribution of scrub typhus in Hangzhou City.Methods:The case information of scrub typhus in Hangzhou City from 2010 to 2022 was collected through the Infectious Disease Surveillance and Reporting Information System of China Disease Prevention and Control Information System, and the incidence, time, population, and regional distribution characteristics of scrub typhus were analyzed. With street (township) as the unit, ArcGIS 10.2 software was used for global and local spatial autocorrelation analysis, SaTScan 10.1.2 software was used for spatio-temporal aggregation scanning.Results:From 2010 to 2022, a total of 362 cases were reported in Hangzhou City, with a median annual incidence of 0.260/100 000. The incidence showed a fluctuating upward trend year by year ( Z = 3.84, P < 0.001). The highest incidence was 0.528/100 000 in 2021 and the lowest incidence was 0.013/100 000 in 2010. The median time interval between onset and diagnosis was 7 days, ranging from 1 to 28 days. The peak incidence period was from September to November (52.49%, 190/362). There were 149 males (41.16%, 149/362) and 213 females (58.84%, 213/362). The age group of 60 - 69 years old had the highest number of cases, accounting for 32.32% (117/362). The majority of occupations were farmers (77.35%, 280/362). The top 3 regions with reported cases were Chun'an County (257 cases, 70.99%), Lin'an District (33 cases, 9.12%), and Jiande City (19 cases, 5.25%). Global spatial autocorrelation analysis showed that there was spatial aggregation in the incidence of scrub typhus in other years except 2015 - 2018 ( P < 0.05). Local spatial autocorrelation analysis showed that, except for 2015 and 2016, the incidence of scrub typhus in other years occurred in hot spots (high-high), which were all located in Chun'an County. The spatio-temporal aggregation analysis showed that the class Ⅰ cluster was centered around Jinfeng Township in Chun'an County, with a clustering period from December 2018 to November 2021, involving 22 townships. The class Ⅱ cluster was centered around Wanshi Township in Fuyang District, with a clustering period from December 2021 to November 2022, involving 14 streets (townships). Both of the two clusters were mountainous agricultural areas, with reported cases accounting for 38.67% (140/362). Conclusions:In Hangzhou City, the majority of scrub typhus cases are elderly female farmers, with a high incidence season in autumn, mainly occurring in agricultural areas in mountainous areas. It is recommended to carry out comprehensive prevention and control measures such as health education and personal protection for key populations, seasons and regions.

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 variation pattern of real-ear-to-coupler difference(RECD)in chil-dren,and to compare it with the standard values of Western children.Thus,to provide a basis for the establishment of the standard values of RECD in children in China.Methods A total of 120 children participated in this study,and were divided into 8 groups according to the test age.Binaural RECD tests were performed for each group at each frequency.The standard values established for Western children were compared,and their variation patterns were analyzed.Results The mean values of RECD in Chinese children were generally lower than the standard values of RECD in Western children.There were no significant differences in RECD values between 3～6 and 7～11 months of age,and between 18～23 and 24～35 months of age.RECD values decreased gradually with the age of children.There were no statistical differences in RECD values between the right and left ears of children.Conclusion Indi-vidual RECD values should be measured during hearing aid fitting.In addition,one ear value can be used for both ears for children who have difficulty in completing binaural testing.

Objective:To analyze the clinical characteristics of patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR), and to explore the risk factors leading to poor prognosis.Methods:The clinical data of 95 patients with ECPR admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to May 2023 were retrospectively analyzed. According to the survival status at the time of discharge, the patients were divided into the survival group and death group. The difference of clinical data between the two groups was compared to explore the risk factors related to death and poor prognosis. Risk factors associated with death were identified by Binary Logistic regression analysis. Results:A total of 95 patients with ECPR were included in this study, 62 (65.3%) died and 33 (34.7%) survived at discharge. Patients in the death group had longer low blood flow time [40 (30, 52.5) min vs. 30 (24.5, 40) min ] and total cardiac arrest time[40 (30, 52.5) min vs. 30(24.5, 40) min], shorter total hospital stay [3 (2, 7.25) d vs. 19 (13.5, 31) d] and extracorporeal membrane oxygenation (ECMO) assisted time [26.5 (17, 50) h vs. 62 (44, 80.5) h], and more IHCA patients (56.5% vs. 33.3%) and less had spontaneous rhythm recovery before ECMO (37.1% vs. 84.8%). Initial lactate value [(14.008 ± 5.188) mmol/L vs.(11.23 ± 4.718) mmol/L], APACHEⅡ score [(30.10 ± 7.45) vs. (25.88 ± 7.68)] and SOFA score [12 (10.75, 16) vs. 10 (9.5, 13)] were higher ( P< 0.05). Conclusions:No spontaneous rhythm recovery before ECMO, high initial lactic acid and high SOFA score are independent risk factors for poor prognosis in ECPR patients.

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.
Infant, Newborn ; Humans ; Hair Cells, Auditory, Inner/physiology* ; Ear, Inner/physiology* ; Hair Cells, Auditory/physiology* ; Regeneration/genetics* ; Stem Cells

Objective To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Methods Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson’s trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Results Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson’s trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm² and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm² and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). Conclusions E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

Septic shock has always been a challenging problem for people,with a high incidence rate and mortality.After decades of development,significant progress has been made in the pathophysiology and clinical aspects of septic shock.The"Surviving Sepsis Campaign"guidelines provide a suitable approach to directing treatment,enabling earlier recognition of septic shock and reducing its mortality rate.However,there are still many challenges,such as refractory septic shock(RSS)and multiple organ failure.Over the past decade,extracorporeal membrane oxygenation(ECMO)technology has been increasingly applied in the treatment of critically ill patients.Whether ECMO can be considered as a salvage treatment for RSS is increasingly being considered.This report presents the experience of successfully treating a patient with RSS using ECMO in our department.For the management of RSS,it is recommended to consider ECMO as a worthwhile option,providing some practical experience for the treatment of RSS with ECMO.