Objective To investigate the effects of perampanel on the C-C chemokine receptor 5(CCR5)/cAMP-dependent protein kinase A(PKA)/cyclic-AMP response binding protein(CREB)pathway and hippocampal neuronal damage in epileptic rats.Methods Seventy-two male SPF-grade SD rats were randomly divided into epilepsy group,perampanel group,CCR5 inhibitor(maraviroc)group,recombinant CCL5 protein(rCCL5,CCR5 activator)group,perampanel+rCCL5 group,and a control group,with 12 rats in each group.The duration and frequency of epi-leptic seizures were detected in above groups.HE staining was used to observe the morphology of the hippocampal CA1 region.ELISA was employed to measure the contents of cyclooxygenase-2(COX-2),TNF-α,and IL-18 in the hippocampal CA1 region.Western blotting was conducted to measure the expression levels of CCR5,PKA,and p-CREB in the hippocampal CA1 region.Results Compared with the control group,the epilepsy group demonstrated badly-arranged and swollen neurons in the hippocampal CA1 region,longer duration of epilepsy,higher seizure frequency,increased COX-2,TNF-α and IL-18 contents in the CA1 region,elevated apoptotic rate and CCR5 protein level,and prolonged escape latency,while less number of crossing platforms and reduced protein levels of PKA and p-CREB(P＜0.05).While,both perampanel and maraviroc treatment could reverse above indicators when compared with the levels of the epilepsy group(P＜0.05).In the rCCL5 group,the neural injury was significantly aggravated,the duration of epilepsy and the frequency of epileptic seizures were increased,the contents of COX-2,TNF-α and IL-18 in the hip-pocampal CA1 region were enhanced,the rate of neuronal apoptosis and the expression of CCR5 protein were significantly enhanced,the escape latency was prolonged,and the number of crossed platforms,PKA,and the expression of p-CREb protein were declined(P＜0.05).When compared with the perampanel group,addition of rCCL5 resulted prolonged duration of epilepsy and escape latency,increased frequency of epileptic seizures and protein levels of COX-2,TNF-α,IL-18 and CCR5,more severe neuronal injury in the CA1 region,less platforms crossed,and decreased pro-tein expression of PKA and p-Creb(P＜0.05).The neural apoptotic rate in the hippocampal CA1 region was significantly higher in the perampanel+rCCL5 group than the perampanel group[(10.58±0.43)％vs(6.36±0.31)％,P＜0.05].Conclusion Perampanel may inhibit neuroin-flammation and neuronal apoptosis in epileptic rats by down-regulating CCR5 and then activating the PKA/CREB pathway,and thus attenuate hippocampal neuronal damage.

Objective:To study the effect and mechanism of ganoderma lucidum polysaccharide peptide(GLPP)on renal anti oxidative stress and immune inflammation in diabetes nephropathy mice.Methods:The C57 male mice model of diabetes nephropathy was established by streptozotocin combined with high glucose and high-fat diet.Sixty diabetes nephropathy mice were divided into model group,losartan group,GLPP group(low,medium and high dose groups),GLPP high-dose+losartan group,with 10 mice in each group,10 mice fed with normal diet as the blank group.The losartan group was given 10 mg/kg losartan by gavage,and GLPP low,medium and high dose groups was given 50,100,and 200 mg/kg GLPP by gavage,while the GLPP high-dose+losartan group were given 200 mg/kg GLPP+10 mg/kg losartan by gavage.The blank group and model group were given physiological saline by gavage.After gastric lavage,observe the diet,water intake,renal pathology,structure,and apoptosis of renal tubular epithelial cells in mice,and analyze the levels of blood biochemical indicators,immune inflammation,oxidative stress indicators,and expression of apoptosis/cycle regulatory proteins in mice.Results:Compared with the blank group,the model group showed an increase in blood biochemical indicators such as Scr,BUN,TC,TG and GSP(P<0.05),as well as inflammation indicators such as level of IL-6 and TNF-α、MCP-1 were decreased(P<0.05),the oxidative stress indicator MDA was increased,T-AOC,GSH-PX,SOD were decreased(P<0.05),the apoptosis rate of renal tubular epithelial cells were increased(P<0.05),the expression levels of Bax,Caspase-3,P53,P21 were all increased,and the expression levels of Bcl-2 and Cyclin D1 were decreased(P<0.05).Compared with the model group,the losartan group,GLPP dose groups,GLPP high-dose+losartan group Scr,BUN,TC,TG,GSP,IL-6,TNF-α,MCP-1,MDA levels,apoptosis rate of renal tubular epithelial cells,Bax,Caspase-3,P53,P21 expression levels were all reduced,while T-AOC,SOD,GSH-PX levels,Bcl-2,and Cyclin D1 expression levels were all increased.Renal pathological changes were improved,and mitochondrial swelling was reduced.The GLPP high-dose+losartan group showed the most significant improvement(P<0.05).Conclusion:GLPP can reverse the renal injury in diabetes nephropathy mice,which may be related to the inhibition of apoptosis of renal tubular epithelial cells by alleviating renal oxidative stress and immune inflammatory damage.

Objective:To study the effect and mechanism of ganoderma lucidum polysaccharide peptide(GLPP)on renal anti oxidative stress and immune inflammation in diabetes nephropathy mice.Methods:The C57 male mice model of diabetes nephropathy was established by streptozotocin combined with high glucose and high-fat diet.Sixty diabetes nephropathy mice were divided into model group,losartan group,GLPP group(low,medium and high dose groups),GLPP high-dose+losartan group,with 10 mice in each group,10 mice fed with normal diet as the blank group.The losartan group was given 10 mg/kg losartan by gavage,and GLPP low,medium and high dose groups was given 50,100,and 200 mg/kg GLPP by gavage,while the GLPP high-dose+losartan group were given 200 mg/kg GLPP+10 mg/kg losartan by gavage.The blank group and model group were given physiological saline by gavage.After gastric lavage,observe the diet,water intake,renal pathology,structure,and apoptosis of renal tubular epithelial cells in mice,and analyze the levels of blood biochemical indicators,immune inflammation,oxidative stress indicators,and expression of apoptosis/cycle regulatory proteins in mice.Results:Compared with the blank group,the model group showed an increase in blood biochemical indicators such as Scr,BUN,TC,TG and GSP(P<0.05),as well as inflammation indicators such as level of IL-6 and TNF-α、MCP-1 were decreased(P<0.05),the oxidative stress indicator MDA was increased,T-AOC,GSH-PX,SOD were decreased(P<0.05),the apoptosis rate of renal tubular epithelial cells were increased(P<0.05),the expression levels of Bax,Caspase-3,P53,P21 were all increased,and the expression levels of Bcl-2 and Cyclin D1 were decreased(P<0.05).Compared with the model group,the losartan group,GLPP dose groups,GLPP high-dose+losartan group Scr,BUN,TC,TG,GSP,IL-6,TNF-α,MCP-1,MDA levels,apoptosis rate of renal tubular epithelial cells,Bax,Caspase-3,P53,P21 expression levels were all reduced,while T-AOC,SOD,GSH-PX levels,Bcl-2,and Cyclin D1 expression levels were all increased.Renal pathological changes were improved,and mitochondrial swelling was reduced.The GLPP high-dose+losartan group showed the most significant improvement(P<0.05).Conclusion:GLPP can reverse the renal injury in diabetes nephropathy mice,which may be related to the inhibition of apoptosis of renal tubular epithelial cells by alleviating renal oxidative stress and immune inflammatory damage.

Objective To investigate the effects of perampanel on the C-C chemokine receptor 5(CCR5)/cAMP-dependent protein kinase A(PKA)/cyclic-AMP response binding protein(CREB)pathway and hippocampal neuronal damage in epileptic rats.Methods Seventy-two male SPF-grade SD rats were randomly divided into epilepsy group,perampanel group,CCR5 inhibitor(maraviroc)group,recombinant CCL5 protein(rCCL5,CCR5 activator)group,perampanel+rCCL5 group,and a control group,with 12 rats in each group.The duration and frequency of epi-leptic seizures were detected in above groups.HE staining was used to observe the morphology of the hippocampal CA1 region.ELISA was employed to measure the contents of cyclooxygenase-2(COX-2),TNF-α,and IL-18 in the hippocampal CA1 region.Western blotting was conducted to measure the expression levels of CCR5,PKA,and p-CREB in the hippocampal CA1 region.Results Compared with the control group,the epilepsy group demonstrated badly-arranged and swollen neurons in the hippocampal CA1 region,longer duration of epilepsy,higher seizure frequency,increased COX-2,TNF-α and IL-18 contents in the CA1 region,elevated apoptotic rate and CCR5 protein level,and prolonged escape latency,while less number of crossing platforms and reduced protein levels of PKA and p-CREB(P＜0.05).While,both perampanel and maraviroc treatment could reverse above indicators when compared with the levels of the epilepsy group(P＜0.05).In the rCCL5 group,the neural injury was significantly aggravated,the duration of epilepsy and the frequency of epileptic seizures were increased,the contents of COX-2,TNF-α and IL-18 in the hip-pocampal CA1 region were enhanced,the rate of neuronal apoptosis and the expression of CCR5 protein were significantly enhanced,the escape latency was prolonged,and the number of crossed platforms,PKA,and the expression of p-CREb protein were declined(P＜0.05).When compared with the perampanel group,addition of rCCL5 resulted prolonged duration of epilepsy and escape latency,increased frequency of epileptic seizures and protein levels of COX-2,TNF-α,IL-18 and CCR5,more severe neuronal injury in the CA1 region,less platforms crossed,and decreased pro-tein expression of PKA and p-Creb(P＜0.05).The neural apoptotic rate in the hippocampal CA1 region was significantly higher in the perampanel+rCCL5 group than the perampanel group[(10.58±0.43)％vs(6.36±0.31)％,P＜0.05].Conclusion Perampanel may inhibit neuroin-flammation and neuronal apoptosis in epileptic rats by down-regulating CCR5 and then activating the PKA/CREB pathway,and thus attenuate hippocampal neuronal damage.

Reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) have garnered significant attention in cancer research because of their potential for precise spatiotemporal drug release tailored to high ROS levels within tumors. Despite the challenges posed by ROS distribution heterogeneity and endogenous supply constraints, this review highlights the strategic alliance of ROS-responsive DDSs with photodynamic therapy (PDT), enabling selective drug delivery and leveraging PDT-induced ROS for enhanced therapeutic efficacy. This review delves into the biological importance of ROS in cancer progression and treatment. We elucidate in detail the operational mechanisms of ROS-responsive linkers, including thioether, thioketal, selenide, diselencide, telluride and aryl boronic acids/esters, as well as the latest developments in ROS-responsive nanomedicines that integrate with PDT strategies. These insights are intended to inspire the design of innovative ROS-responsive nanocarriers for enhanced cancer PDT.

Objective:To explore the genotypes and clinical phenotypes of three families with Liddle Syndrome(LS).Methods:In this study, three young patients with hypertension and hypokalemia were confirmed LS through second-generation sequencing genetic testing. Members of the three families were screened for genes, and genotypes and clinical phenotypes were analyzed.Results:This study identified three patients in Family 1 carrying a possible pathogenic heterozygous variant c. 1859A>G(p.Y620C) in the SCNN1B gene(sodium channel epithelia 1β subunit). Five patients in family 2 and family 3 carried the pathogenic heterozygous variant c. 1789dup(p.R597Pfs*11) in the SCNN1B gene. Following three months of treatment with salt restriction and triamterene, blood pressure and potassium levels returned to normal in all eight patients.Conclusion:LS patients typically present clinically with early-onset hypertension accompanied by hypokalemia, but there is clinical heterogeneity. It is recommended to conduct genetic testing on suspected patients as early as possible to confirm the diagnosis and initiate timely treatment with effective medications so as to reduce the complications of target organs.

OBJECTIVE: To establish a method for directional screening of the cytotoxic components from the medicinal herb of Achnatherum inebrians by a combination of surface plasmon resonance (SPR) biosensor and chromatographic isolation technology. METHODS: Under the guidance of bioactive assessment based on binding abilities between objects and the α-Mannosidase (α-Man) target, the active components from different solvents extracts, different polar extraction parts and fractions were screened orderly and directionally using SPR. Components with a high binding ability to α-Man can be precisely oriented in a narrower fractions range and are easy to isolate. Three human cancer cells were used to evaluate the cytotoxic activity of component with the highest affinity to α-Man. RESULTS: Eight compounds were isolated and identificated from A. inebrians for the first time. Deoxyvasicinone possessed the highest affinity to α-Man among them. Moreover, deoxyvasicinone showed good effects on inhibited proliferation of human hepatoma cells HepG2 (IC₅₀ = 5.7 μmol/L), human breast cancer cells MCF7 (IC₅₀ = 7.21 μmol/L) and human lung cancer cells HCC827 (IC₅₀ = 0.75 μmol/L), respectively. In particular, its inhibitory effect on HCC827 was stronger than the positive drug gefitinib (IC₅₀ = 1.65 μmol/L). CONCLUSION A comprehensive strategy of directional screening potential cytotoxic components from herb based on biomolecular interaction and chromatography was established. Deoxyvasicinone as an effective anti-cancer component was initially isolated from A. inebrians. It is expected that this screening strategy could provide new perspectives for rapid screening and identification of active components from natural plants with the complex matrix.

Recently, monkeypox has become a global concern amid the ongoing COVID-19 pandemic. Monkeypox is an acute rash zoonosis caused by the monkeypox virus, which was previously concentrated in Africa. The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person. We need to revisit this virus to prevent the epidemic from getting worse. In this review, we comprehensively summarize studies on monkeypox, including its epidemiology, biological characteristics, pathogenesis, and clinical characteristics, as well as therapeutics and vaccines, highlighting its unusual outbreak attributed to the transformation of transmission. We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.
COVID-19 ; Disease Outbreaks/prevention & control* ; Humans ; Monkeypox/epidemiology* ; Monkeypox virus ; Pandemics/prevention & control*

【Objective】 To provide reference for formulating relatively unified quality control strategies and meeting the requirements of homogenization construction of blood banks across Chongqing area by retrospectively analyzing sampling results of different blood components during the past two years in all levels of blood banks in Chongqing area. 【Methods】 The key quality data of blood components prepared by 6 blood banks in Chongqing were analyzed retrospectively. According to the issuing units to the clinical during the past two years, the research objects were selected as leukocyte-depleted suspended RBCs, cryoprecipitate, pathogen inactivated fresh frozen plasma(FFP) and apheresis platelets. The quality data of the above-mentioned blood components from January 2019 to June 2021 were collected and analyzed. 【Results】 For leukocyte-depleted suspended RBCs(1U)prepared by 5 blood banks, statistically significant differences in Hb, residual white blood cells and hemolysis rate at the end of storage, except for Hct, were noticed(P<0.05). For cryoprecipitate, the content of blood coagulation factor Ⅷ and fibrinogen were statistically different among 3 blood banks in 1U specification(P<0.05) and among 5 blood banks in 2U specification(P<0.05). For pathogen inactivated FFP, the content of blood coagulation factor Ⅷ, plasma proteins, and residual methylene blue were statistically different among 3 blood banks(P<0.05). For apheresis platelets, Plt, white/red blood cells contamination and pH at the end of storage were statistically different among 3 blood banks(P<0.05). 【Conclusion】 The quality data of blood components, prepared by different blood banks, meet the requirements of national standard, however, certain differences are existing among blood banks.Key points during the process of collection, preparation, storage and transportation need to be cleared and unified, so as to reduce the differences between each other, and determine the direction and basis for homogeneity construction in the next step.

Objective: To investigate the role of BRAF^V600E mutation in diagnosis of thyroid nodules when it is inconsonant with cytological results. Methods: This study included 9837 patients who underwent US-FNA. We mainly analyzed 239 cases with benign or indeterminate cytology, but having a detection of BRAF^V600E mutation. BRAF^V600E mutation analysis was performed using a Amplification Refractory Mutation System Polymerase Chain Reaction. Results: In 93 nodules with benign cytology results but positive BRAF^V600E mutation, 84 nodules were malignant. Based on the results, US-FNA combined with BRAF^V600E mutation analysis will improve sensitivity (Se=94.03%) and negative predictive value (NPV=2.69%) of the thyroid nodules diagnosis than using US-FNA alone (Se=71.03%, NPV=20.76%) . Conclusion BRAF^V600E mutation analysis is an important tool in the diagnosis of PTC with high sensitivity and NPV. When facing patients with benign or indeterminate cytology but positive BRAF^V600E mutation, thyroidectomy should be considered.