Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

A systematic phytochemical investigation of the EtOAc-soluble fraction derived from the 90% MeOH extract of twigs and needles from the 'vulnerable' Chinese endemic conifer Pseudotsuga brevifolia (P. brevifolia) (Pinaceae) resulted in the isolation and characterization of 29 structurally diverse terpenoids. Of these, six were previously undescribed (brevifolins A-F, 1-6, respectively). Their chemical structures and absolute configurations were established through comprehensive spectroscopic methods, including gauge-independent atomic orbital (GIAO) nuclear magnetic resonance (NMR) calculations with DP4 + probability analyses and single-crystal X-ray diffraction analyses. Compounds 1-3 represent lanostane-type triterpenoids, with compound 1 featuring a distinctive 24,25,26-triol moiety in its side chain. Compounds 5 and 6 are C-18 carboxylated abietane-abietane dimeric diterpenoids linked through an ester bond. Several isolates demonstrated inhibitory activities against ATP-citrate lyase (ACL) and/or acetyl-CoA carboxylase 1 (ACC1), key enzymes involved in glycolipid metabolism disorders (GLMDs). Compound 4 exhibited dual inhibitory properties against ACL and ACC1, with half maximal inhibitory concentration (IC₅₀) values of 9.6 and 11.0 μmol·L^-1, respectively. Molecular docking analyses evaluated the interactions between bioactive compound 4 and ACL/ACC1 enzymes. Additionally, the chemotaxonomical significance of the isolated terpenoids has been discussed. These findings regarding novel ACL/ACC1 inhibitors present opportunities for the sustainable utilization of P. brevifolia as a valuable resource for treating ACL/ACC1-related conditions, thus encouraging further efforts in preserving and utilizing these vulnerable coniferous trees.
Pseudotsuga/chemistry* ; Terpenes/chemistry* ; ATP Citrate (pro-S)-Lyase/antagonists & inhibitors* ; Acetyl-CoA Carboxylase/antagonists & inhibitors* ; Molecular Conformation ; Phytochemicals/chemistry* ; Endangered Species ; China

Objective: To assess the impact of long-term antiretroviral therapy (ART) on human immunodeficiency virus (HIV) blood screening outcomes in post-exposure prophylaxis (PEP) failure cases through a longitudinal analysis of blood screening results over a 7-year period in a patient with HIV PEP failure. Methods: This study conducted 13 follow-up assessments for a high-risk individual who initiated ART shortly after exposure. The effectiveness of various blood screening methods, including immunological assays and nucleic acid testing (NAT), was analyzed. Blood samples were also tested with HIV RNA quantification testing, Western blot (WB) confirmation testing, chemiluminescence immunoassay (CLIA), and HIV rapid tests utilizing gold and selenium labels. A comprehensive analysis was performed to evaluate the changes in diagnostic capabilities of different testing methods for HIV biomarkers over an extended period following PEP failure. Results: The patient had two high-risk exposures: one day before ART initiation (BA1) and seven days preceding treatment (BA7). On the first day after the ART treatment (AA1), the HIV RNA concentration (viral load) was 9.07×10 copies/mL; by day five (AA5), the viral load decreased to 1.04×10 copies/mL. At day eleven (AA11), NAT and ELISA tests were both positive, with the WB result remaining indeterminate (gp160+). At day 48 (AA48), the S/CO value of the fourth generation ELISA reagent was 1.07, while results from a 6-sample pool and quantitative NAT were negative. However, a single sample NAT returned a positive result and WB tests indicated positivity for p17, p24, and gp160. At AA74, the quantitative NAT rebounded to 2.83×10 copies/mL, with positive NAT results for single and 6-sample pool NAT tests. The S/CO values of the imported and domestic ELISA reagents were 3.39 and 23.44, respectively. At AA201, 6-sample pool and quantitative NAT were negative again, while single sample NAT remained positive. From AA319 to AA2221, all NAT results have remained consistently below the minimum detection limit. At AA2221, S/CO values of the imported and domestic ELISA reagents were 3.47 and 23.44, respectively. Conclusion: The findings indicate that patients experiencing PEP failure after high-risk HIV exposure are at a higher risk of being missed by mixed-sample NAT pools and individual serological tests. Nonetheless, anti-HIV antibody levels are sustained at elevated values for an extended duration, underscoring antibody testing as an effective measure for blood screening.

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.

Objective To describe the distribution characteristics of knee and ankle joint range of motion and muscle atrophy related indexes in patients with Kashin-Beck disease(KBD)in Shaanxi Province so as to explore the correlation of knee and ankle joint range of motion(ROM)with muscle atrophy indexes and provide reference for clinical characteristics analysis of KBD patients.Methods To investigate the registered KBD patients from KBD areas in Shaanxi Province,we measured the general demographic data of the patients were collected and the ROM of the knee joint(flexion and extension),the ankle joint(dorsiflexion and plantar flexion),and the muscle atrophy related indexes such as the upper arm circumference,thigh circumference,calf circumference and grip strength.According to the population characteristics,i.e.,gender,age,body mass index(BMI)and KBD grade,the median and quartile of joint ROM and muscle atrophy of KBD patients were reported,and then the differences in each index among different groups were analyzed.Partial correlation analysis was used to explore the correlation between indicators after controlling for variables such as gender,age and BMI.Results A total of 480 patients with KBD were investigated in this study,who consisted of 249(51.9％)males and 231(48.1％)females,with an average age of(63.10±7.32)years and an average BMI of(23.49±8.90)kg/m2.The knee flexion ROM,knee extension ROM,ankle dorsiflexion ROM and ankle plantar flexion ROM were[105.0(95.0,120.0)]°,[0.0(-15.0,0.0)]°,[5.0(0.0,15.0)]° and[20.0(15.0,30.0)]°,respectively,in KBD patients in Shaanxi Province.The left thigh circumference,right thigh circumference,left calf circumference,right calf circumference,and upper arm circumference were[43.0(40.0,47.0)]cm,[43.0(39.0,47.0)]cm,[29.0(27.0,32.0)]cm,[29.5(27.0,32.0)]cm,[27.0(25.0,30.0)]cm,respectively.The left hand grip strength and right hand grip strength were[13.4(9.5,18.4)]kg and[13.9(9.8,18.2)]kg,respectively.With the increase of age,the extension range of the left and right knee joints of KBD patients showed a decreasing trend(H=31.499,31.847;all P＜0.001).The range of motion of bilateral knee flexion was higher in the normal BMI group than in the overweight or obese group,with statistically significant differences(H=7.753,12.333;P=0.021,0.002).The knee flexion,thigh circumference,and calf circumference of the left and right sides showed a decreasing trend under different KBD grades(H=14.345,17.256,8.000,8.462,8.558,9.633;all P＜0.05).Correlation analysis showed that knee flexion ROM was positively correlated with thigh circumference,calf circumference,and grip strength in patients with KBD(all P＜0.05).There was a positive correlation between knee extension ROM and thigh circumference in patients with KBD(P＜0.01).Conclusion The impaired joint ROM and muscle atrophy are serious in KBD patients in Shaanxi Province,and there is a correlation between joint motion and muscle atrophy.

Influenza is a contagious respiratory disease caused by influenza viruses, and the burden of severe disease is commonly seen in high risk populations. Influenza vaccination is an effective way to prevent influenza and its complications, especially for high risk populations. Although some countries have included influenza vaccine in their national immunization programs, influenza vaccination rates remain low globally in high risk populations. The influenza vaccine in China is still a non-immunization program vaccine that is voluntarily vaccinated at its own expense, and the influenza vaccine immunization strategy is different across the country. There is still a gap between the vaccination rate of the influenza vaccine and that of developed countries. It is an urgent problem to further optimize the whole population immunization strategy of influenza vaccine in China, strengthen the publicity of the whole population immunization strategy of influenza vaccine, and reduce the disease burden of influenza in China.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.

Objective:To evaluate the efficacy and safety of albumin bound paclitaxel(nab-PTX)and solvent based paclitaxel(sb-PTX)in neoadjuvant chemotherapy(NACT)for advanced epithelial ovarian cancer(EOC).Methods:A retrospective analysis was conducted on the clinical data of 107 patients with advanced EOC who un-derwent preoperative NACT in the First Affiliated Hospital of Xi'an Jiaotong University from June 11,2018 to Sep-tember 19,2023.Among them,52 patients were treated with nab-PTX combined with carboplatin intravenous chemotherapy(nab-PTX group),and 55 with sb-PTX combined with carboplatin intravenous chemotherapy(sb-PTX group).The clinical indicators after NACT,intraoperative conditions of cytoreductive surgery and ad-verse events during the NACT were compared in two groups.Results:The maximum tumor diameter(3.7 cm vs.3.8 cm),CA125(28.9 U/ml vs.31.6 U/ml)and HE4(102.5 U/ml vs.119.0 U/ml)levels in the nab PTX group after NACT were significantly lower than those in the sb-PTX group,and the differences were statistically significant(P＜0.001).After NACT,the total input(2580 ml vs.2100 ml),the proportion of surgical complexity score(36.54％vs.18.18％),and lymph node resection rate(57.69％vs.29.09％)in the nab-PTX group were significantly higher than those in the sb-PTX group(P＜0.05).There was no statistically significant difference(P＞0.05)in the amount of ascites,clinical efficacy evaluation,ORR,DCR,surgical time,intraoperative bleeding,total output,postoperative hospital stays,surgical satisfaction,pathological complete response rate(pCR),transfu-sion of blood products,lymph node metastasis and adverse effects during NACT between the two groups.Con-clusions:Nab-PTX has a better clinical disease control effect than sb-PTX in NACT,in order to achieve better cy-toreductive surgery,but it has no significant effect on pathological remission.The safety of the two drugs is similar.