HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Gastric cancer （GC） is a digestive tract tumor that occurs in the epithelial tissues of the gastric mucosa， seriously affecting the life and health of patients， and its mortality rate ranks the third among malignancies. Although medical technology has made great progress in recent years， the progression of GC still cannot be effectively controlled by surgery， chemotherapy， and targeted therapy. The pathogenesis of GC is extremely complex and is closely related to the tumor microenvironment， chronic inflammation， and immune escape， among which the reduction of tumor cell apoptosis is one of the important mechanisms for the occurrence and development of GC. Apoptosis refers to the process of spontaneous termination of cell life caused by genes under specific physiological or pathological conditions， which is of great significance for maintaining the stability of the internal environment. Researchers have found that in the GC state， mitochondrial endogenous apoptosis， endoplasmic reticulum stress， external death receptors， and other apoptosis pathways are regulated by multiple signaling pathways and genes， which together lead to the decline of GC cell apoptosis rate and thus promote the progression of GC. Chinese medicine is advantageous and characterized by multiple components， multiple targets， synergistic effect， and few adverse reactions. A large number of studies have shown that polysaccharide components， as effective components of Chinese medicine， have biological activities such as cancer inhibition， blood sugar control， anti-inflammation， antioxidant damage， and anti-virus， and can effectively inhibit the deterioration of GC by inducing cell apoptosis， gradually becoming a hot spot in GC drug research and development. However， systematic reviews on the apoptosis of GC induced by Chinese medicine polysaccharides are rarely reported. Therefore， this paper analyzed and summarized the studies of Chinese medicine polysaccharides in promoting apoptosis and interfering with GC， in order to provide a theoretical basis for the basic research， new drug development， and clinical application of Chinese medicine polysaccharides in the intervention of GC.

Objective:To understand the prevalence of arboviruses in mosquito samples in Xichang City, Sichuan Province, and enrich the data of arbovirus activity and genetic characteristics in southwestern Sichuan Province.Methods:In June 2018, the nucleic acid was extracted from Culex tritaeniorhynchus mosquitoes collected from different pigsties in three villages and suburbs of Xichang City. The specific primers of Yunnan orbivirus, Banna virus, Tibet orbivirus (S7, S10), Flavivirus and alphavirus were used for quantitative polymerase chain reaction examination, and the positive product was cloned for sequencing analysis. Results:A total of 9 012 mosquitoes were collected, of which Cx. tritaeniorhynchus was the dominant species. A number of 88 batches of these mosquitoes were amplified, and 2 strains of Japanese encephalitis virus (JEV), 7 strains of Banna virus (BAV), 7 strains of Tibet orbivirus (TIBOV) and 1 strain of Yunnan orbivirus virus (YOUV) were detected, respectively. By the results of cluster analysis and evolutionary tree analysis, the 17 newly found virus strains were close to the Yunnan isolates, and 2 JEV strains were located in the GI-b clade. The other 7 strains of BAV were A2 evolutionary clades. Of the 7 TIBOV plants, 6 were located in the same clade. One TOUV was in the same clade as the Yunnan strain. Conclusions:Culex tritaeniorhynchus mosquitoes in Xichang city might carry JEV, BAV, YOUV and TIBOV, among them JEV was GI-b type and BAV was A2 type. The results provide data supporting the detection and analysis of arboviruses in Xichang city.

Objective To preliminarily understand the infection of Chikungunya virus (CHIKV) in Cangyuan County, a southern border area of Yunnan Province, and provide a reference basis for the prevention and control of Chikungunya fever. Methods In April 2020, a total of 400 serum samples from individuals seeking medical care at the People's Hospital of Cangyuan County in Yunnan Province were collected. Among these, 121 samples were from healthy individuals undergoing physical examinations, and 279 samples were from patients with fever. The serum samples collected underwent CHIKV neutralizing antibody testing using a serum micro-neutralization assay. Real-time fluorescence quantitative RT-PCR was used to detect CHIKV nucleic acid in the samples, followed by analysis of the test results. Results The results of neutralizing antibodies showed that 18 of the 400 human serum samples were positive for neutralizing antibodies against CHIKV, with an overall positivity rate for serum samples of 4.5% (18/400). Among the 279 serum samples collected from patients with fever, 18 were positive for neutralizing antibodies against CHIKV, with a positive rate of 6.45% (18/279), and the neutralizing antibody titers ranged from 1∶10 to 1∶320. The results of 121 healthy human serum samples were negative for neutralizing antibodies against CHIKV. The results of real-time fluorescence quantitative RT-PCR showed that 3 of the 400 human serum samples were positive for CHIKV nucleic acid, and the positive rate was 0.75% (3/400). Among the 279 serum samples collected from patients with fever, 3 samples were positive for CHIKV nucleic acid, with a positive rate of 1.08% (3/279), and Ct values ranged from 36.58 to 37.74. While all healthy human serum samples were negative for CHIKV nucleic acid. Conclusions The findings indicate that infection of CHIKV exists in the population of Cangyuan County, a southern border area of Yunnan Province, and an outbreak of the disease is occurring. Therefore, it is necessary to strengthen the monitoring, prevention, and control of CHIKV in this area.

Objective This study aims to comprehensively investigate the molecular characteristics of the predominant circulating Dengue virus type 1 (DENV-1) during the 2019 Dengue fever outbreak in Xishuangbanna, providing an essential insight to support the prevention and control of dengue fever in the local area. Methods A Dengue virus type 1 (DENV-1) strain, designated as JHS45, isolated from the blood of a febrile patient in Xishuangbanna in 2019, underwent a process of inoculation and cultivation in C6/36 cells. Second-generation sequencing was employed to capture the viral genetic sequence. Bioinformatics software, including CLC, was used for assembling the sequencing data. Sequentially, sequence alignment, construction of a phylogenetic tree, and analysis of amino acid sites were conducted using software such as Lasergene and MEGA6.1. Results Cytopathic effects of JHS45 appeared in C6/36 cells after 6 days. After sequencing and assembly, a 10 687-nucleotide (nt) long sequence of the JHS45 virus was obtained (GenBank accession number: OR593353). Genetic evolutionary analysis revealed that the JHS45 virus formed an evolutionary branch with DENV-1 genotype I viruses prevalent in Xishuangbanna, Guangzhou, Henan, and Zhejiang in China during 2019, as well as the DENV-1 genotype I virus prevalent in Thailand in 2013, with nucleotide homology of 97.6% to 99.9% and amino acid homology of 99.1% to 100%. Further analysis revealed that the JHS45 strain shared a smaller evolutionary branch with the DENV-1 genotype I viruses prevalent in Xishuangbanna (MW386863) and Guangzhou (MW261839) in 2019, showing the highest homology with nucleotide and amino acid homology of 99.9% and 100%, respectively. Amino acid differential site analysis between the JHS45 strain and the DENV-1 prevalent in Xishuangbanna since 2015 revealed 40 amino acid differential sites in the coding region of the JHS45 virus, primarily concentrated in the NS3 and NS5 regions of non-structural proteins. Conclusion The comprehensive analysis of the JHS45 strain's whole genome sequence indicates it is a DENV-1 genotype I virus. The genetic evolutionary relationship between this Xishuangbanna dengue fever outbreak is closely related to the prevalent virus strains in Xishuangbanna, Guangzhou, Henan, and Zhejiang. These findings provide a robust scientific foundation for monitoring dengue fever outbreaks, conducting virus evolution studies, and shaping effective prevention and control strategies, not only within Yunnan Province but also on a broader scale throughout China.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

During the COVID-19 epidemic, our national guidelines have suggested that surgical patients should wear a mask to decrease the potential transmission of COVID-19 in the operating room, as long as the condition allows. However, so far, there is no study to discuss the influence of wearing a mask on the ventilation and blood oxygenation status in patients of spontaneous breathing with supplementary oxygen through an anesthetic facemask. This is a before-after study in the same patient, and 10 healthy volunteers were recruited, by testing the arterial blood gas parameters at key time points before and after oxygen inhalation to evaluate the effects of two different supplementary oxygen methods ('disposable medical mask + anesthetic facemask' and 'anesthetic facemask only') on the oxygenation of subjects. Our data demonstrated whether wearing a disposable medical mask or not could effectively increase the oxygen supply of the subjects compared with the basic value before oxygen inhalation; however, compared with the group without mask, the arterial oxygen partial (PaO
COVID-19 ; Healthy Volunteers ; Humans ; Masks ; Oximetry ; Oxygen/blood*

Objective:To study the prevalence of Akabane virus (AKAV) in Yunnan province.Methods:A group of sentinel animals including 5 goats and 10 cattles which were sero-negative for bluetongue virus and AKAV were located in Mangshi, Yunnan province, to monitor arbovirus activity from April to October 2015. The heparin-anticoagulated blood of the animals was collected weekly for arbovirus isolation. Erythrocytes were lysed in distilied water and inoculated onto BHK-21 monolayer for virus isolation. After the cells showed cytopathic effect (CPE), AKAV in the cell cuture were identified by RT-PCR amplification with AKAV S gene segment specific primers and gene sequencing.Results:The result indicated that BHK-21 cell inoculated with the blood from one sentinel goat showed CPE 48 h post inoculation. One day old suckling mice intracerebrally inoculated with the supernatant of the cell culture, they started to become sick and died after 3 days. RT-PCR identification and S gene sequencing showed that the isolate was AKAV (numbered as 16415). The full length of S segment gene of 16415 is 856 nt, encoding 233 amino acids of protein N, and 91 amino acids of protein Ns. Phylogenetic analysis showed that, among the AKAV strains isolated from China and abroad, the newly isolated 16415 was in the same branch with the other viruses in different geographical regions, and their S segment nucleotide sequence have a high homology of 83.8%-97.7%. The further study show that 16415 and the AKAV isolated from the domestic bamboo rat in Guangxi in 2013 have a closest realtionship in evolution, the nucleotide sequence homology was 97.7%, and amino acid homology is 99.6%. Compared with the Japanese OBE-1 strain, the amino acids of protein N of 16415 and the AKAVs, isolated from banboo rat in Guangxi and Anopheles vagas in Mangshi of Yunnan province of China, have two common diverse amino acids loci located at the 115th and 206th sites respectively. Conclusions:It is concluded that AKAV was newly isolated from goat in Mangshi of Yunnan province, which may have important epidemiological significance.

Objective:To explore arboviruses carried by midges in Shizong county, Yunnan province.Methods:A total of 74 batches of 3705 midges collected from Shizong county, Yunnan province in July 2013 were detected by RT-PCR method, and then the amplified bands were cloned and sequenced. MegAlign in DNAStar software was used for homology analysis, MEGAX software ALIGN for sequence alignment and genetic evolution analysis based on Maximum Likelihood (ML) method .Results:Among 74 batches of midge samples collected in Yunnan province, 600 bp electrophoresis bands were amplified in 3 batches: SZC33, SZC42 and SZ625C8-2, while no electrophoresis bands were amplified in the other 71 batches of midge samples. After cloning, we selected 5 clones for sequencing, among which the 5 clones of sample SZC42 obtained 589 nt sequences. BLASTx comparison showed that the 5 cloned sequences of SZC42 had the highest amino acid homology(69%) with the non-structural protein gene of Culex bastrovirus-like(CAVL) virus found in mosquitoes collected in the United States, which was designated as Midge bastrovirus-like virus (MAVL). The result of genetic evolution analysis showed that MAVL detected in midges formed a single evolutionary branch, and it’s homology of nucleotides and amino acids with other astrovirus(AV) was less than 71.4%. Further analysis revealed that MAVL had a close genetic evolution relationship with CAVL (NC_040647) detected in American mosquitoes, AV (MF042208) detected in Brazilian sewage and AV (NC_032426) detected from Vietnamese bats, and the homology was 61.4%-66.2% (nt) and 67.7%-71.4% (aa), while far genetic evolution and low homology of nucleotides and amino acids with other AV sirains.Conclusions:A new astrovirus (MAVL) was detected in midges collected from Shizong county, Yunnan province in 2013.

Aim To investigate the effect of salvianolate syophilized injection on brain tissue gene expression profiles in stroke of diabetic rats.Methods T1DM was induced in adult male Wistar rats by injecting streptozotocin.T1DM rats were then subjected to 90 minutes of middle cerebral artery occlusion(MCAO).The rats were randomly assigned to sham group(DM+Sham),ischemia-reperfusion group(DM+ MCAO/R),edaravone group(6 mg·kg-1,ED)and salvianolate lyophilized injection treatment group(5.25,10.5,21 mg·kg-1,SLI)with 13 rats in each group.Drugs were administered by tail vein injection 3 hours after MCAO/R,daily and lasting for 14 days.Infarct volume and gene expression in the brain tissue were detected by TTC staining and the gene chip technique.Results Compared with DM+Sham group,67 differential expressed genes were detected in the DM+MCAO/R group,among which 41 genes were up-regulated and 26 genes were down-regulated.Compared with DM+MCAO/R group,59 differential expressed genes were detected in the SLI(21 mg·kg-1)group,among which 45 genes were up-regulated and 14 genes were down-regulated.Hierarchical cluster results suggested that a number of genes were significantly changed in T1DM rats,such as Ly6i,Pax7 and Irx2.Effects of SLI on the stroke in T1DM rats were majorly related to coagulation and hemostasis system,inflammatory cytokines,oxidative stress,substance metabolism,angiogenesis and signal transduction.Conclusion Salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in type 1 diabetic rats through regulation of the coagulation and hemostasis system,inflammatory cytokines,oxidative stress,substance metabolism,angiogenesis and signal transduction.