Objective To examine the association between epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) and meteorological factors in Shenzhen City during the period from 2012 to 2019. Methods Average atmospheric pressure, average air temperature, average relative humidity, precipitation, wind speed, and sunshine duration were captured from Meteorological Bureau of Shenzhen City each month from 2012 to 2019. The average monthly rodent densities in Shenzhen City from 2012 to 2019 were acquired from the Vector Surveillance Management System of Guangdong Provincial Center for Disease Control and Prevention, and the monthly HFRS incidence was retrieved from Shenzhen Municipal Disease Surveillance System from 2012 to 2019. The correlation between meteorological factors and the monthly incidence of HFRS was examined us ing Spearman’s rank correlation in Shenzhen City, and the temporal trends in monthly HFRS incidence and the degrees of freedom for the rodent density were determined in Shenzhen City with a generalized additive model. The optimal lag time was identified using excess risk (ER) and its 95% confidence interval (CI), and univariate and multivariate models were fitted to evaluate the impact of meteorological factors on HFRS incidence in Shenzhen City. Results The median number of incident HFRS cases was 3.00 (interquartile range, 3.25) in Shenzhen City from 2012 to 2019, with an average air temperature of (23.44 ± 4.91) °C, average relative humidity of (76.05 ± 7.61)%, median precipitation of 4.10 (interquartile range, 6.83) mm, average wind speed of (1.97 ± 0.26) m/s, average sunshine duration of (5.17 ± 1.64) h, and median monthly rodent density of 1.74% (interquartile range, 2.52%). Spearman’s rank correlation analysis showed that the average air temperature positively correlated with average relative humidity (r_s = 0.420, P < 0.05), precipitation (r_s = 0.658, P < 0.05) and sunshine duration (r_s = 0.633, P < 0.05), and the atmospheric pressure negatively correlated with average air temperature (r_s = −0.925, P < 0.05), relative humidity (r_s = −0.614, P < 0.05), precipitation (r_s = −0.789, P < 0.05) and sunshine duration (r_s = −0.437, P < 0.05), while the average relative humidity correlated positively with precipitation (r_s = 0.724, P < 0.05) and negatively with sunshine duration (r_s = −0.218, P < 0.05). Univariate modeling analysis showed that the ERs and their 95% CI were 0.639% (0.540%, 0.737%) for average atmospheric pressure, −7.157% (−8.113%, −6.190%) for average air temperature, −3.603% (−4.219%, −2.985%) for average relative humidity, −5.889% (−7.085%, −4.669%) forprecipitation,21.881% (−5.149%, 56.612%) for average wind speed, and −13.877% (−16.641%, −11.022%) for sunshine duation (all P values < 0.05). Multivariate modeling analysis showed that in the ensemble model combining average atmospheric pressure and precipitation, the highest ER (6.686%) was caused by increased average atmospheric pressure, and the highest absolute ER values for average air temperature (6.615%), average relative humidity (3.107%) and precipitation (5.386%) were seen after adjustment only for sunshine duration (all P values < 0.05), while the highest absolute ER for sunshine duration (11.875%) was found after adjustment for precipitation (P < 0.05). Conclusions An increase in average air temperature, relative humidity, precipitation and sunshine duration resulted in a reduced incidence rate of HFRS in Shenzhen City from 2012 to 2019, and an increase in average atmospheric pressure increased the incidence of HFRS. Meteorological factors are important determinants affecting HFRS incidence in Shenzhen City.

This article discusses the important role and practical experience of Guangxi Zhuang Autonomous Region as a bridgehead between China and the Association of Southeast Asian Nations (ASEAN) in the joint prevention and control of cross-border infectious diseases between China and Vietnam. The cross-border transmission of infectious diseases has been effectively managed in Guangxi Zhuang Autonomous Region through a package of strategies, including government leadership, construction of the joint prevention and control mechanism, establishment of dialogue platforms, collaboration of scientific researches, and personnel exchange and training; however, there are still challenges. Further deepening of collaboration is required to meet future needs for infectious disease prevention and control.

Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1％),and CDKN2A homozygous deletion(36.8％)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P＜0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.

Purpose To analyze and discuss the clinicopathological,molecular pathological characteristics,as well as diagnostic and prognostic features of pleomorphic xanthoastrocytoma(PXA)according to the new WHO classifi-cation.Methods 79 cases of PXA were collected to analyze their pathological and clinical data.Immunohistochemis-try using the EnVision method was employed to detect the expression of CD34,ATRX,Rb,Olig-2,H3K27M,H3K27me3,IDH1 R132H,BRAF VE1 and Ki67.Sanger sequencing was used to detect mutations in H3F3A and IDH1/2.Fluorescence quantitative PCR was used to detect the BRAF V600E mutation and TERT promoter region al-terations.Fluorescence in situ hybridization(FISH)was used to detect CDKN2A and EGFR alterations.The relation-ship between clinical,pathological,molecular genetics data,and prognosis was analyzed.Results The patients'ages ranged from 9 to 69 years,with an average age of 36.4 years.Most tumors were located in the temporal lobe,frontal lobe and parietal lobe.Among the 79 cases,42 were classified as grade 2 PXA and 37 as grade 3 PXA.The tumor cells exhibited pleomorphic changes,with perivascular lymphocytic sheaths and eosinophilic bodies frequently ob-served.Grade 3 PXA exhibited more mitotic figures(average of 11.8/10 HPF),and was usually accompanied by nec-rosis,focal marginal infiltration and microvascular proliferation.Immunohistochemistry and molecular characteristics revealed frequent positivity for CD34,BRAF V600E mutation(68.1％),and CDKN2A homozygous deletion(36.8％)in PXA.Some cases showed TERT gene mutation and absent Rb expression.Univariate survival analysis in-dicated that necrosis,focal marginal infiltration,and CNS WHO grade were related to overall survival,while focal infil-tration and CNS WHO grade were the independent risk factors.Conclusion The prognosis of CNS WHO grade 3 PXA is wrose than that of grade 2 PXA.Accurate diagnosis of PXA requires the combination of the morphological features,immunohistochemical staining,and multiple molecular tests.

Objective:The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis.Methods:This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data.Results:The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients ( P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis ( P＜0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients ( P=0.017). Conclusions:The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.
Anilides/pharmacology* ; Cerebral Hemorrhage/drug therapy* ; Hematoma/drug therapy* ; Humans ; Macrophages ; Microglia ; Neuroprotection ; PPAR gamma ; Retinoid X Receptor alpha

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.

Objective To analyze the clinical courses and outcomes of COVID-19 cases and the influencing factors in Guangdong province and provide basis for the formulation or adjustment of medical care and epidemic control strategy for COVID-19. Methods We collected demographic data, medical histories, clinical courses and outcomes of 1 350 COVID-19 patients reported in Guangdong as of 4 March 2020 via epidemiological investigation and process tracking. Disease severity and clinical course characteristics of the patients and influencing factors of severe illness were analyzed in our study. Results Among 1 350 cases of COVID-19 cases in Guangdong, 72 (5.3%) and 1049 (77.7%) were mild and ordinary cases, 164 (12.1%) were severe cases, 58 (4.3%) were critical cases and 7 (0.5%) were fatal. The median duration of illness were 23 days ( P 25 - P 75 : 18-31 days) and the median length of hospitalization were 20 days ( P 25 - P 75 : 15-27 days). For severe cases, the median time of showing severe manifestations was on the 12th day after onset ( P 25 - P 75 : 9th to 15th days), and the median time of severe manifestation lasted for 8 days P 25 - P 75 : 4-14 days). Among 1 066 discharged/fetal cases, 36.4% (36/99) and 1.0% (1/99) of the mild cases developed to ordinary cases and severe cases respectively after admission; and 5.2% (50/968) and 0.6% (6/968) of the ordinary cases developed to severe cases, and critical cases respectively after admission. In severe cases, 11.4% developed to critical cases (10/88). The influencing factors for severe illness or worse included male (a HR =1.87, 95% CI : 1.43-2.46), older age (a HR =1.67, 95% CI : 1.51-1.85), seeking medical care on day 2-3 after onset (a HR =1.73, 95% CI : 1.20-2.50) pre-existing diabetes (a HR =1.75, 95% CI : 1.12-2.73) and hypertension (a HR =1.49, 95% CI : 1.06-2.09). Conclusions The course of illness and length of hospitalization of COVID-19 cases were generally long and associated with severity of disease clinical outcomes. The severe cases were mainly occurred in populations at high risk. In the epidemic period, classified management of COVID-19 cases should be promoted according to needs for control and prevention of isolation and treatment for the purpose of rational allocation of medical resources.

Objective:To evaluate the effect of orexin-A on programmed necrosis during cerebral ischemia-reperfusion (I/R) in rats.Methods:Thirty clean-grade healthy adult male Spraugue-Dawley rats, weighing 280-320 g, were divided into 3 groups ( n=10 each) using a random number table method: sham operation group (Sham group), cerebral I/R group (I/R group) and orexin-A group (OA group). In I/R and OA groups, a rat model of global cerebral I/R injury was established by transesophageal cardiac pacing-induced cardiac arrest and cardiopulmonary resuscitation in anesthetized animals.Orexin-A 30 μg/kg (diluted to 0.5 ml in phosphate buffer solution) was intravenously injected at 10 min before establishing the model in OA group.Phosphate buffer solution 0.5 ml was intravenously injected at 10 min before establishing the model in Sham and I/R groups.The neurological deficit score (NDS) was assessed at 24 h of reperfusion, then the rats were sacrificed, and bilateral hippocampal tissues were obtained.The morphological structure of pyramidal cells in the hippocampal CA1 region was examined after HE staining, and normal pyramidal cells were counted.Western blot was used to detect the expression of receptor-interacting protein 1 (RIP1), RIP3 and mixed-lineage kinase domain-like protein (MLKL). Immuno-histochemistry was used to count RIP1, RIP3 and MLKL positive cells in the hippocampal CA1 region.The activity of superoxide dismutase (SOD) in hippocampi was determined by xanthine oxidase method, and the content of malondialdehyde (MDA) in hippocampi was determined by thiobarbituric acid method. Results:Compared with Sham group, the normal pyramidal cell count in the hippocampal CA1 region was significantly decreased, NDS was increased, the expression of RIP1, RIP3 and MLKL protein was up-regulated, the positive cell count was increased, the content of MDA in hippocampi was increased, and the activity of SOD in hippocampi was decreased in I/R and OA groups ( P<0.05). Compared with I/R group, the count of normal pyramidal cells in the hippocampal CA1 region was significantly increased, NDS was decreased, the expression of RIP1, RIP3 and MLKL protein was down-regulated, the count of positive cells was decreased, the content of hippocampal MDA was decreased, and the activity of hippocampal SOD was increased in OA group ( P<0.05). Conclusion:The mechanism by which orexin-A reduces cerebral I/R injury may be related to inhibiting programmed necrosis in rats.