Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

OBJECTIVE: To investigate the effects of histone deacetylase (HDAC) levels on the proliferation and apoptosis of Burkitt lymphoma cells, and the changes in related signaling molecules in the PI3K/AKT/mTOR signaling pathway, so as to explore the pathogenesis of Burkitt lymphoma. METHODS: HDAC levels in Burkitt lymphoma were detected by RT-PCR and Western blot. CA46 and RAJI cells were treated with the HDAC selective inhibitor VPA. CCK8 assay was used to detect the proliferation ability of cells. Western Blot was used to measure the expression of apoptosis-related proteins, PI3K/AKT/mTOR signaling pathway proteins and their phosphorylation levels. RESULTS: The expression levels of classⅠ HDAC in Burkitt lymphoma were higher than those in normal cells, and the HDAC1 inhibitor VPA could inhibit the proliferation of CA46 and RAJI cells. VPA decreased HDAC expression in CA46 and RAJI cells, inhibited the phosphorylation of PI3K/AKT/mTOR pathway molecules AKT and p70S6K, increased the expression of apoptotic proteins Cleaved Caspase-3, Cleaved Caspase-8, Cleaved Caspase-9 and Bax, and decreased the expression of anti-apoptotic proteins Bcl-2 and PARP. CONCLUSION Inhibition of HDAC activity can Attenuate the proliferation of Burkitt lymphoma cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway activity.
Humans ; Burkitt Lymphoma/pathology* ; Apoptosis ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Histone Deacetylases/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Phosphorylation

Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective:To study the reversal effect of NVP-BEZ235 on doxorubicin resistance in Burkitt lymphoma RAJI cell line.Methods:The doxorubicin-resistant cell line was induced by treating RAJI cells with a concentration gradient of doxorubicin.The levels of Pgp,p-AKT,and p-mTOR in cells were detected by Western blot.Cell viability was detected by MTT assay.IC50 was computed by SPSS.Results:The doxorubicin-resistant Burkitt lymphoma cell line,RAJI/DOX,was established successfully.The expression of Pgp and the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line were both higher than those in RAJI cell line.NVP-BEZ235 downregulated the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line.NVP-BEZ235 inhibited the proliferation of RAJI/DOX cell line,and the effect was obvious when it was cooperated with doxorubicin.Conclusion:The constitutive activation of PI3K/AKT/mTOR pathway of RAJI/DOX cell line was more serious than RAJI cell line.NVP-BEZ235 reversed doxorubicin resistance of RAJI/DOX cell line by inhibiting the PI3K/AKT/mTOR signal pathway.

Humans ; Stomach Neoplasms/pathology* ; Neoadjuvant Therapy ; Chemotherapy, Adjuvant ; Gastrectomy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

To make up for the shortcomings of traditional mild moxibustion, according to the principle and technical operation characteristics of traditional mild moxibustion, combined with temperature control technology, a novel infrared mild moxibustion device is developed, which is capable of real-time accurate temperature control. This novel infrares mild moxibustion device is composed of a host computer and an infrared radiation head. The host computer includes four modules: power supply, human-computer interaction interface, micro control unit (MCU) and drive circuit. The infrared radiation head mainly includes an infrared heater and a temperature sensor. This novel infrared mild moxibustion device is easy to operate. The electrothermal heating tablet can generate infrared radiation of 3 000-13 000 nm. After the temperature of the infrared heater is stabilized, the range of temperature change is ±0.50 ℃, realizing the goal of precise temperature control. In addition, it can operate moxibustion treatment at multiple acupoints at the same time, which is conducive to the dose-effect evaluation of mild moxibustion.
Humans ; Moxibustion ; Acupuncture Points ; Temperature ; Heating

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.