Objective To study the population genetic structure and phylogenetic relationships by combining Y-STR haplotype genetic information from the Han population in Dalian with 32 domestic and foreign groups.Methods Blood samples of 958 Han male volunteers from Dalian were collected.Genetic typing of 42 genetic loci was completed using Y-STR fluorescent reagent kits and capillary electrophoresis.Related forensic parameters were calculated.Nei's standard genetic distances among 33 populations based on 17 Y-STR loci were computed,in order to create a principal coordinate analysis as well as construct a phylogenetic tree.Results The analysis of genetic polymorphisms at 42 Y-STR loci revealed 30 unconventional alleles at 10 loci.Genetic analysis of the population based on 17 Y-STR loci confirmed that Dalian's Han population had the closest genetic distance to the Anshan's Han population,followed by populations from Henan,Heilongjiang,Jilin,Shandong,and Chongqing.Furthermore,the genetic distances between the Han population in Dalian and the Qiang population in Beichuan or the Miao population in Guizhou were relatively closer than that to the Manchu population living in Liaoning.Conclusion The genetic distance between the Han population in Dalian and other groups is not entirely proportional to ethnicities and geographical proximity.Both population migration and ethnic assimilation or isolation may have influence on it.

Objective To explore the effect of protective ventilation strategies based on individualized positive end expiratory pressure(PEEP)regulated by driving pressure(Pd)in infants under OLV.Methods Sixty infants undergoing elective thoracoscopic surgery were randomly divided into the control group and driving pressure group,with 30 cases in each group.The two groups were compared in terms of MAP,HR,tidal volume(Vt),PEEP,Pd,airway peak pressure(Ppeak),and static lung compliance(Cs),and arterial blood gas during OLV before the artificial pneumothorax(T0),10 min(T1),30 min(T2),and 60 min(T3)after the artificial pneumothorax,and right at the end of the artificial pneumothorax(T4).Results There were no significant differences in MAP,HR,and Vt between the two groups at all the time points(P＞0.05).Both groups showed the increase in Pd and Ppeak and decresase in Cs at T1,T2,and T3(all P＜0.05).PaO2 and OI in both group were decreased and PaCO2 was increased at T2(all P＜0.05).Compared with the control group,the driving pressure group presented lower Pd and Ppeak,higher PEEP and Cs at T1,T2,and T3(P＜0.05),and higher PaO2 and OI(P＜0.05)and no significant differences in PaCO2 and FiO2 at T2(P＜0.05).The rate of rescue ventilation during OLV was lower in the driving pressure group(2 cases)than in the control group(9 cases)(6.9%versus 32.4%,P＜0.05).There was no significant difference in the inci-dence of postoperative complications between the two groups(P＜0.05).Conclusion The individualized positive end expiratory pressure(PEEP)regulated by Pd can optimize the PEEP settings upon infant individuals under OLV and improve the compliance and oxygenation of ventilated lung.

Ginger mainly contains two main categories of volatile and non-volatile components,of which the non-volatile gingerol is a general term for pungent substances in ginger,mainly containing gingerols,shogaols and other components,with a wide range of pharmacological effects.By reviewing the 2020 edition of the Pharmacopoeia of the People's Republic of China and related literature in Chinese databases such as CNKI and Wanfang,it was found that the use of the Chinese names of gingerols and shogaols was confusing,which caused certain troubles to readers and obstacles to academic exchanges.According to the naming principles of Chinese medicinal extracts,it is suggested that gingersols,6-gingerol,8-gingerol and 10-gingerol should be uniformly named as gingerols(姜酚类),6-gingerol(6-姜酚),8-gingerol(8-姜酚)and 10-gingerol(10-姜酚),respectively,and shogaols and 6-shogaol should be uniformly named as shogaols(姜烯酚类)and 6-shogaols(6-姜烯酚).The standardized use of the Chinese names of gingerols and shogaols will facilitate in-depth research and academic exchange on ginger,dried ginger,baked ginger and other ginger herbal medicines.

Objective:To investigate the lipidomics differences of CD4+T immune cells in diabetic kidney disease(DKD)mice,and screen out the differential metabolites with biological significance.Methods:CD4(L3T4)MicroBeads immunomagnetic beads were used to isolate CD4+T immune cells from spleen of BKS.Cg-Dock7m+/+Leprdb/J mice with spontaneous DKD;the purity of CD4+T cells were identified by flow cytometry.The non-targeted lipidomics of CD4+T cells were detected by LC-MS/MS,and the differ-ential metabolites were analyzed.Results:A total of 463 metabolites were detected by LC-MS.PCA and OPLS-DA analysis showed that the metabolic components were significantly separated;twenty-four differential metabolites were screened out.KEGG and enrich-ment analysis showed that the differential metabolites involved in the disorder of glycerol phospholipid metabolism.Conclusion:Phos-pholipid metabolism of CD4+T cells is closely related to the occurrence of DKD.Phospholipid metabolism targeting DKD CD4+T cells in DKD may be a new direction of DKD treatment.

The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.

Objective:To investigate the impact of residual cholesterol (RC) on the progression of arteriosclerosis in individuals receiving physical examination.Methods:A cross-sectional study. Participants aged 18 years and above who underwent arteriosclerosis testing at the Health Management Center of Zigong Fourth People′s Hospital from January to December 2023 were selected as the subjects of the study. A total of 9 016 subjects were included in this study, of whom 6 213 were considered to have arteriosclerosis. The physical examination conclusions, basic information (age, gender, body mass index, waist circumference, blood pressure, history of hypertension, history of smoking and drinking), and biochemical indicators (lipids, fasting blood glucose, liver and kidney function) were extracted in those individuals. Based on the examination results, the subjects were categorized into arteriosclerosis and normal groups. The RC levels of the participants were calculated using a formula and then the subjects were categorized into binary and quartile RC groups. Additionally, four regression models were used to analyze the impact of RC levels on the progression of arteriosclerosis while adjusting for various confounding factors.Results:The RC level was (0.63±0.44) mmol/L in the normal group and (0.76±0.61) mmol/L in the arteriosclerosis group. Based on level of RC, the normal group was divided into two subgroups: 652 individuals with elevated RC level and 2 241 with normal RC level. In the arteriosclerosis group, there were 2 069 individuals with elevated RC level and 4 144 with normal RC level. Grouped according to quartiles of RC level, the number of individuals with RC in the Q1-Q4 interval in the normal group was 838 (28.97%), 752 (25.99%), 760 (26.27%), and 543 (18.77%), respectively, showing a gradual decreasing trend. The number of individuals with RC in the Q1-Q4 interval in the arteriosclerosis group was 1 414 (22.76%), 1 438 (23.15%), 1 589 (25.58%), and 1 771 (28.51%), respectively, showing a gradual increasing trend. The difference between the groups was statistically significant ( P<0.05). After adjusting for various factors by four regression models, it was found that elevated RC levels increased the risk of arteriosclerosis progression, with a odds ratio ( OR) of 1.381, 1.242, 1.233, and 1.214, respectively. Additionally, individuals in the Q4 RC level quartile had 1.502, 1.318, 1.311, and 1.284-times higher risk of arteriosclerosis progression when compared to those in the Q1 quartile. Conclusion:The impact of RC on the progression of arteriosclerosis tend to stabilize and remain consistent, indicating that elevated RC is an independent risk factor for the progression of arteriosclerosis.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 µg/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 µg/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

PD-1 and PD-L1 together constitute the stimulus signaling pathway of adaptive immune response, which has been widely used in the research on the mechanism of tumor immune escape and tumor therapy. At the same time, its signaling pathway has been proved to be closely associated with the immune escape of hepatic echinococcosis. This article reviews the chemical structures of PD-1 and PD-L1, the mechanism of the PD-1/PD-L1 signaling pathway, and the role of the PD-1/PD-L1 signaling pathway in immune escape of hepatic echinococcosis, i.e., the PD-1/PD-L1 signaling pathway is involved in immune escape of hepatic echinococcosis under three theories, so as to explore the immune escape of hepatic echinococcosis from a new perspective and provide a basis and ideas for the diagnosis and treatment of hepatic echinococcosis.

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.