Objective To evaluate the potential risk of transmission of angiostrongyliasis by common freshwater snails in Dali Bai Autonomous Prefecture, Yunnan Province, so as to provide insights into local surveillance of angiostrongyliasis. Methods Common freshwater snails were collected from Dali Bai Autonomous Prefecture, Yunnan Province from March to April, 2020, and identified and bred in laboratory. SD rats were infected with third-stage larvae of Angiostrongylus cantonensis that were isolated from commercially available Pomacea canaliculata snails in Dali Bai Autonomous Prefecture, and freshwater snails were infected with the first-stage larvae of A. cantonensis that were isolated from the feces of SD rats 39 days post-infection at room temperature. The developmental process and morphological characteristics of worms in hosts were observed, and the percentages of A. cantonensis infections in different species of freshwater snails were calculated. Then, SD rats were infected with the third-stage larvae of A. cantonensis that were isolated from A. cantonensis-infected freshwater snails, and the larval development and reproduction was observed. Results More than 3 000 freshwater snail samples were collected from farmlands, ditches and wetlands around Erhai Lake in Dali Bai Autonomous Prefecture, and Cipangopaludina chinensis, P. canaliculata, Parafossarulus striatulus, Oncomelania hupensis robertsoni, Galba pervia, Physa acuta, Radix swinhoei, Assiminea spp., Tricula spp. and Bellamya spp. were morphologically identified. A total of 105 commercially available P. canaliculata snails were tested for A. cantonensis infections, and 2 P. canaliculata snails were found to be infected with A. cantonensis, in which the third-stage larvae of A. cantonensis were isolated. Ten species of freshwater snails were artificially infected with the third-stage larvae of A. cantonensis, and all 10 species of freshwater snails were found to be infected with A. cantonensis, with the highest positive rate of A. cantonensis infections in Bellamya spp. (62.3%, 137/204), and the lowest in C. chinensis (35.5%, 11/31). After SD rats were infected with the third-stage larvae of A. cantonensis isolated from different species of freshwater snails, mature adult worms of A. cantonensis were yielded. Conclusions Multiple species of freshwater snails may serve as intermediate hosts of A. cantonensis under laboratory conditions in Dali Bai Autonomous Prefecture of Yunnan Province. Further investigations on natural infection of A. cantonensis in wild snails in Dali Bai Autonomous Prefecture seem justified.

Objective To investigate the reliability and feasibility of spectral entropy in evaluate the effectiveness of analgesic sedation in patients with ischemic stroke.Methods A total of 64 patients with acute ischemic stroke admitted to Hongqi Hospital Affiliated to Mudanjiang Medical University from July 2021 to November 2022 were selected as study objects,and the included patients were divided into control group and experimental group according to random number table method,with 32 cases in each group.Patients in control group adjusted analgesia and sedation regimen according to Richmond agitation-sedation scale(RASS)score and critical-care pain observation tool(CPOT)score.Patients in experimental group adjusted the analgesic and sedation regimen according to the results of spectral entropy.The vital signs,C-reactive protein(CRP),dose of sedative and analgesic drugs and incidence of adverse reactions were compared between two groups.The correlation between spectral entropy and RASS score and CPOT score was used Spearman correlation analysis.Results The spectral entropy values were positively correlated with the RASS score and CPOT score,respectively(r=0.719,0.556,P<0.001).There were no significant differences in mean arterial pressure and percutaneous arterial oxygen saturation between two groups at different time points(P>0.05).The heart rate at T3 in experimental group was significantly lower than that in control group(P<0.05).At T1,T2 and T3,CRP levels in experimental group were significantly lower than those in control group(P<0.05).The dosage of sufentanil and midazolam in experimental group were significantly lower than those in control group(P<0.05).The incidence of adverse reactions in experimental group was significantly lower than that in control group(12.50%vs.34.38%,χ2=4.267,P=0.039).Conclusion Spectral entropy can be used as an objective method to monitor the depth of analgesia and sedation in patients with ischemic stroke,and has a good correlation with RASS score and CPOT score,which can reduce the incidence of adverse reactions,effectively avoid stress reactions,and reduce the application of analgesia and sedation drugs.

Objective:To explore the relationship between the expressions of P21,P27 and proliferating cell nuclear antigen(PCNA)in glomerular mesangial tissue and poor renal prognosis in patients with immunoglobulin A(IgA)nephropathy.Methods:A total of 145 patients with IgA nephropathy treated in Xiaogan Central Hospital from April 2017 to August 2019 were selected as the research object.The expressions of P21,P27 and PCNA in glomerular mesangial tissue were detected by immunohistochemistry.All patients were followed up for 24 months,and the prognosis were counted.The expressions of P21,P27 and PCNA in glomerular mesangial tissue of patients with different prognosis were compared and the influencing factors of poor prognosis in patients with IgA nephropathy were analyzed by Logistic regression analysis.Results:The expression rates of P21,P27 and PCNA positive cells in glomerular mesangial tissue of patients with IgA nephropathy were(38.69±6.83)%,(55.94±8.08)%,(33.47±5.72)%,respectively.The incidence rete of poor prognosis in patients with IgA nephropathy was 17.24%,and the expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of patients with poor prognosis were higher than those in good prognosis group(P<0.05),while the expression rate of P27 positive cells was lower than that in good prognosis group(P<0.05).Logistic multiple regression analysis showed that elevated diastolic blood pressure,increased 24 h proteinuria,mesangial cell proliferation,segmental glomerulosclerosis,renal tubular atrophy/interstitial fibrosis,crescentic body,increased expression rates of P21 and PCNA positive cells and decreased expression rate of P27 positive cells were all risk factors affecting the poor prognosis of patients with IgA nephropathy(P<0.05).Conclusion:There are positive expressions of P21,P27 and PCNA in glomerular mesangial tissue of IgA nephropathy.The expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of of patients with poor prognosis of IgA nephropathy are higher than those with good prognosis,while the expression rate of P27 protein positive cells is lower than those with good prognosis,which are risk factors for poor prognosis of patients with IgA nephropathy.

The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.
Humans ; Cell Cycle/physiology* ; Cell Division ; Cyclin-Dependent Kinases/metabolism* ; Cyclins/metabolism*

OBJECTIVE To analyze the situation of drug use in medical institutions of Guangdong area from 2017 to 2022， and to provide reference for the production， sale and procurement of drugs by government departments， medical insurance departments， pharmaceutical enterprises， drug sales enterprises and hospitals. METHODS Using the retrospective analysis method， based on original data from Guangdong hospital information network from 2017 to 2022， statistical analysis was conducted on the drug procurement amount of 118 medical institutions that had been online for the past 6 years， as well as the distribution of 14 major categories of drugs among all purchased drugs by online medical institutions， and sales amount of drug production enterprises. RESULTS The drug procurement amount of 118 medical institutions that had been online in Guangdong area from 2017 to 2022 showed a growth-negative growth-slow growth trend. Among the 14 major categories of drugs， the top 5 drugs in the list of consumption sum were anti-infective drugs， cardiovascular drugs， nervous system drugs， anti-tumor drugs， and digestive system drugs； among the top 200 drugs in terms of procurement amount， three major categories of drugs， namely the anti-infective drugs， anti-tumor drugs and cardiovascular system drugs， occupied the main position. The top 10 drugs in the list of procurement amounts were mainly anti-tumor drugs and cardiovascular system drugs； foreign manufacturers occupied the top 3 places in the list of sales amounts in medical institutions of Guangdong area. CONCLUSIONS In Guangdong area， the growth of drug procurement amount in medical institutions is gradually slowing down， the usage of anti-infective drugs is still abundant， the prevention and treatment of chronic diseases need great attention， and foreign pharmaceutical companies are in a leading position in the sales amount of medical institutions.

Objective:To evaluate the effect of sleep deprivation on cognitive function in septic rats and its relationship with neuronal glycolysis isoenzyme phosphofructokinase-2/fructose-2,?6-diphosphatase 3 (PFKFB3).Methods:Fifty-six healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups ( n = 14): control group (Con group), sepsis group (LPS group), sepsis+sleep deprivation group (LPS+SD group), sepsis+sleep deprivation+glycolysis inhibitor 3-PO treatment group (LPS+SD+3-PO group). The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg. Rats in LPS+SD group were treated with sleep deprivation using a sleep deprivation instrument 24 hours after LPS injection. The LPS+SD+3-PO group was intraperitoneally injected with LPS for 24 hours, and then injected with 3-PO 50 mg/kg, followed by sleep deprivation. Novel object recognition experiments were performed 72 hours after LPS injection. Subsequently, blood and brain tissue samples were collected. The contents of lactate (Lac), reactive oxygen species (ROS) and serum tumor necrosis factor-α(TNF-α), neuron-specific enolase (NSE), pyruvate in brain tissue were detected by enzyme-linked immunosorbent assay (ELISA). Then, the lactate/pyruvate ratio was calculated. Na +-K +-ATPase activity in brain tissue was detected by colorimetry. Morphological changes in hippocampus were detected by hematoxylin-eosin (HE) staining. And the protein expression levels of PFKFB3, ZO-1 and cleaved caspase-3 were measured by Western blotting. Results:Compared with Con group, the novel object recognition index of LPS group was decreased, the levels of NSE, TNF-α, lactate/pyruvate ratio in serum and the levels of Lac, ROS and dry-wet weight ratio in brain tissue were significantly increased, Na +-K +-ATPase activity in brain tissue was decreased, the protein expressions of PFKFB3, caspase-3 were up-regulated, ZO-1 expression was down-regulated, and the neurons in hippocampus were slightly degenerated. Compared with LPS group, the novel object recognition index of LPS+SD group was further decreased [(39.4±5.3)% vs. (54.5±7.6)%)], serum NSE, TNF-α, lactate/pyruvate ratio and brain tissue Lac, ROS, dry-wet weight ratio were further increased [NSE (μg/L): 3.21±0.42 vs. 2.55±0.36, TNF-α (ng/L): 139.4±19.7 vs. 92.2±13.5, lactate/pyruvate ratio: 29.7±5.5 vs. 19.2±4.2, Lac (μmol/g): 19.51±2.33 vs. 11.34±1.52, ROS (kU/g): 117.4±18.7 vs. 78.2±11.8, dry-wet weight ratio: (81.3±9.2)% vs. (64.3±6.6)%], and Na +-K +-ATPase activity was further decreased (mmol·L -1·h -1: 1.88±0.34 vs. 2.91±0.39), the protein expressions of PFKFB3, caspase-3 were further up-regulated and ZO-1 expression was further down-regulated (PFKFB3/β-actin: 0.80±0.11 vs. 0.45±0.07, caspase-3/β-actin: 0.71±0.09 vs. 0.37±0.05, ZO-1/β-actin: 0.31±0.05 vs. 0.61±0.08). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly aggravated. Compared with LPS+SD group, the novel object recognition index of LPS+SD+3-PO group was increased [(50.8±5.9)% vs. (39.4±5.3)%], NSE, TNF-α, lactate/pyruvate ratio of serum and Lac, ROS, dry-wet weight ratio of brain tissue were significantly decreased [NSE (μg/L): 2.60±0.33 vs. 3.21±0.42, TNF-α (ng/L): 103.7±18.3 vs. 139.4±19.7, lactate/pyruvate ratio: 17.4±5.1 vs. 29.7±5.5, Lac (μmol/g): 13.68±2.02 vs. 19.51±2.33, ROS (kU/g): 86.9±14.5 vs. 117.4±18.7, dry-wet weight ratio: (67.7±6.9)% vs. (81.3±9.2)%], and Na +-K +-ATPase activity was increased (mmol·L -1·h -1: 2.82±0.44 vs. 1.88±0.34). The protein expressions of PFKFB3, caspase-3 were down-regulated and ZO-1 expression was up-regulated (PFKFB3/β-actin: 0.50±0.06 vs. 0.80±0.11, caspase-3/β-actin: 0.43±0.06 vs. 0.71±0.09, ZO-1/β-actin: 0.52±0.06 vs. 0.31±0.05). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly improved. Conclusions:Sleep deprivation could aggravate neuroinflammation, neuronal degeneration and apoptosis in septic rats, resulting in destruction of blood-brain barrier and cognitive impairment. 3-PO treatment significantly alleviate the injury and degeneration of hippocampal neurons in septic rats, inhibit neuroinflammation and apoptosis, and improve cognitive dysfunction, which may be related to the inhibition of glycolytic isoenzyme PFKFB3.

Objective:To analyze the types and distribution characteristics of elements in drinking water from endemic fluorosis areas with water improvement in Xi'an City, understand the relationship between fluoride and various elements, and conduct health risk assessment on potential high-risk elements.Methods:From May to June 2017, one endemic fluorosis area with water improvement (Gaoling District, Huyi District, Lintong District) was selected according to the northeast, the southwest and the due east directions of Xi'an City as the survey area. Sixteen endemic fluorosis villages were selected from each endemic area, and 2 water samples were collected from each endemic village to detect fluoride and 12 elements such as chromium, manganese, ferrum, copper, zinc, arsenic, selenium, molybdenum, cadmium, antimony, barium, and lead. Hygienic evaluation was conducted according to national standards, and the potential high-risk elements (arsenic, molybdenum) were assessed for health risk through the health risk assessment model recommended by the National Environmental Protection Agency of the United States.Results:The water samples from the endemic fluorosis areas in Xi'an City mainly contained seven elements: barium, ferrum, molybdenum, arsenic, zinc, manganese, and chromium. The content of copper and selenium was relatively low, while the content of cadmium, antimony, and lead was extremely low. The fluoride content in water samples from Gaoling District and Lintong District was relatively high, and the fluorine, arsenic, molybdenum elements was pairwise positively correlated ( P < 0.05). The molybdenum element in water samples from Lintong District exceeded 9.38% (3/32). The fluoride in the water samples of Huyi District was relatively low, and the arsenic, molybdenum elements was positively correlated ( r = 0.84, P < 0.001), and the arsenic element exceeded the standard by 25.00% (8/32). The main health risk of drinking water in endemic fluorosis areas with water improvement in Xi'an City was arsenic exposure, with children at a higher risk than adults, and the areas of Huyi District, Lintong District, and Gaoling District declined, the risk of cancer (CR) of Gaoling District was < 10 -4 and hazard quotient (HQ) was < 1. However, in the areas of Huyi District and Lintong District (except HQ of adults), there was a higher risk (CR > 10 -4, HQ > 1). Children in one endemic fluorosis village in Lintong District had a higher non carcinogenic risk of molybdenum (HQ > 1). Conclusions:The drinking water in endemic fluorosis areas with water improvement in Xi'an City mainly contains 7 elements, especially arsenic and molybdenum, which need to be regularly monitored. Some areas have high health risks of arsenic in water, and monitoring, management, and related epidemiological investigations need to be strengthened. At the same time, it is necessary to actively monitor other toxic and harmful substances that may be introduced during the water improvement process to prevent the occurrence of secondary health problems.

Objective:To compare the clinical efficacy of laparoscopic inguinal lymph node dissection(L-ILND)and open inguinal lymph node dissection(O-lLND)in the treatment of penile cancer after radical penile cancer surgery. Methods:The clinical outcomes of 63 patients who were diagnosed with penile cancer(TNM staging:T1_3,N0-3,M0)and received L-ILND(41 cases)or O-ILND(22 cases)after radical penile cancer surgery in Department of Urology,Hubei Cancer Hospital,Tongji Medical College,Huazhong University of Science and Technology from 2008 to 2020 were retrospectively studied.The primary endpoint of this study was overall survival,and the secondary endpoints were 5-year overall survival and 5-year cancer-specific survival.The different clinical characteristics were compared between the L-ILND group and O-ILND group.Univariate and multivariate logistic regression analysis was used to study the risk facotrs for postoperative wound complications.Kaplan-Meier method was used for prognosis analysis.COX regression analysis was used to investigate the factors for overall survival prediction. Results:Among the 63 penile cancer patients studied,41 patients received L-ILND and the remaining 22 received O-ILND.There were no statistically significant differences in the baseline characteristics between the two groups of patients.The median overall survival(78 months vs 72 months,P=0.844),5-year overall survival rate(74.5％vs 78.3％,P=0.144),5-year cancer-specific survival rate(77.2％vs 71.4％,P=0.228)showed no obvious difference between L-ILND and O-ILND group.The rate of postoperative wound complications in the O-ILND group was significantly higher than that in the L-ILND group(74％vs 15％,P=0.01 2).The result of multivariate COX regression analysis showed that tumor grade[hazard ratio(H-R)=2.774,P=0.021]and lymph node pathological stage(HR=1.482,P=0.024)were significantly correlated with patients'prognosis. Conclusion:The clinical efficacy of L-ILND and O-ILND is similar,but L-ILND has a higher safety profile and lower incidence of postoperative wound complications.Therefore,L-ILND is a more ideal surgical approach for inguinal lymph node dissection after radical penile cancer surgery.

Humans ; Computational Biology ; Neutrophils/metabolism* ; Sepsis/metabolism* ; Signal Transduction/genetics* ; Immunosuppression Therapy ; Gene Expression Profiling

Bivalves are species-rich mollusks with prominent protective roles in coastal ecosystems.Across these ancient lineages,colony-founding larvae anchor themselves either by byssus produc-tion or by cemented attachment.The latter mode of sessile life is strongly molded by left-right shell asymmetry during larval development of Ostreoida oysters such as Crassostrea hongkongensis.Here,we sequenced the genome of C.hongkongensis in high resolution and compared it to reference bivalve genomes to unveil genomic determinants driving cemented attachment and shell asymmetry.Importantly,loss of the homeobox gene Antennapedia(Antp)and broad expansion of lineage-specific extracellular gene families are implicated in a shift from byssal to cemented attachment in bivalves.Comparative transcriptomic analysis shows a conspicuous divergence between left-right asymmetrical C.hongkongensis and symmetrical Pinctada fucata in their expression profiles.Especially,a couple of orthologous transcription factor genes and lineage-specific shell-related gene families including that encoding tyrosinases are elevated,and may cooperatively govern asymmet-rical shell formation in Ostreoida oysters.