OBJECTIVE To investigate the effects and mechanisms of oliceridine fumarate （TRV130） in improving postoperative cognitive dysfunction （POCD） in elderly rats based on the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） pathway. METHODS Rats were randomly divided into the control group （normal saline）， the model group （normal saline）， the TRV130 group （2.8 mg/kg）， the TLR4/NF-κB pathway inhibitor （TAK-242） group （3 mg/kg）， the β -arrestin inhibitor （Barbadin） group （3 mg/kg）， and the traditional opioid drug （morphine） group （2.8 mg/kg）， with 15 rats in each group. Except for the control group， POCD models were established in all other groups. From the first day after surgery， drugs/normal saline were administered via caudal vein injection once daily for 3 consecutive days. After the last administration， the pathological damage of hippocampal tissue was observed； the cognitive function， serum inflammatory factor levels， hippocampal neurons apoptosis rate， and the expression of ionized calcium-binding adapter molecule 1 （Iba-1）， glial fibrillary acidic protein （GFAP）， and TLR4/NF-κB pathway-related mRNA and protein in hippocampal tissue were detected. RESULTS In the model group， the neurons in the CA1 region of the hippocampus were disordered and sparse， with decreased number， pyknotic and fragmented nuclei accompanied by inflammatory cell infiltration. Compared with the control group， the escape latency， serum levels of tumor necrosis factor α （TNF-α）， interleukin-6 （IL-6）， and IL-1β， hippocampal neurons apoptosis rate， average fluorescence intensities of Iba-1 and GFAP， mRNA expression levels of TLR4 and NF-κB p65， and their protein expression/phosphorylation levels in hippocampal tissue were significantly increased/elevated in the model group （ P ＜0.05）； the time spent in the target quadrant and the number of platform crossings were significantly shortened/decreased （ P ＜0.05）. Compared with the model group， the cognitive function， pathological， inflammatory， and apoptosis-related indicators were significantly improved in the TRV130 group， TAK-242 group， and Barbadin group （ P ＜0.05）； the mRNA expression levels of TLR4 and NF-κB p65 and their protein expression/phosphorylation levels were significantly decreased in the TRV130 group and TAK-242 group （ P ＜0.05）. CONCLUSIONS TRV130 may improve POCD in elderly rats by inhibiting the TLR4/NF-κB pathway and alleviating postoperative central nervous system inflammatory responses.

Psoriasis is a common chronic inflammatory systemic disease in dermatology. Its high prevalence， recurrence rate， and numerous comorbidities impose a significant physical and mental burden on patients. With the continuous advancement of modern medicine， the emergence of biological agents has improved clinical efficacy， making it possible to overcome psoriasis， in addition to classical treatments. However， in clinical practice， adverse reactions， drug resistance， recurrence rates， and immune drift cannot be ignored. Traditional Chinese medicine （TCM） has a history of thousands of years in treating psoriasis， demonstrating good efficacy， high safety， and a low recurrence rate， but a standardized management system is lacking. Therefore， the 25^th Clinical Diseases Responding Specially to TCM Treatment Series （Psoriasis） Youth Salon， hosted by the Chinese Association of Chinese Medicine and organized by the Youth Committee of the Chinese Association of Chinese Medicine， invited 29 experts and scholars from TCM， Western medicine， and interdisciplinary fields to actively discuss the "Advantages， Challenges， and Clinical Transformation of TCM and Western Medicine in the Diagnosis and Treatment of Psoriasis". The experts at the meeting concluded that the advantages of TCM in the treatment of psoriasis are as follows. Firstly， in the TCM-led treatment plan， TCM's understanding of psoriasis follows the principle of combining the differentiation of disease and syndrome. This approach distinguishes the basic contradiction from the current main contradiction and enables a clear grasp of the dynamic process of psoriasis development. Based on the system of syndrome differentiation and treatment， TCM intervention is applied to address the current main contradiction， and the optimal TCM treatment plan is formulated by combining internal and external treatments. Adhering to the principle of "what is visible outside must be addressed inside"， TCM can prevent and treat psoriasis comorbidities early by differentiating syndrome types. Secondly， in the integrated TCM and Western medicine treatment plan， the combination of both methods not only enhances efficacy but also reduces the adverse reactions of immunosuppressants and biological agents， lowering the recurrence rate. This conference provides a reference for the diagnosis and treatment of psoriasis using TCM and integrated TCM and Western medicine， opening up new ideas for clinical and basic research and guiding future research directions.

Objective: To investigate the status and influencing factors of influenza vaccination among the elderly, so as to provide insights into improving the strategies for influenza vaccination among the elderly. Methods: Elderly people aged 60 years and above were recruited from one community each in five sub-districts of Shihezi City, Xinjiang Uygur Autonomous Region using a random sampling method. Demographic information, knowledge about influenza and influenza vaccines, vaccine literacy and influenza vaccination status in the past year were collected through questionnaire surveys. Factors affecting influenza vaccination among the elderly were analyzed using a multivariable logistic regression model. Results: Totally 1 121 valid questionnaires were recovered, with an effective recovery rate of 95.08%. There were 417 males (37.20%) and 704 females (62.80%). The majority were aged 60-<81 years, accounting for 80.37% (901 individuals). The awareness of knowledge about influenza and influenza vaccines was 78.86%. Low vaccine literacy was observed in 786 individuals, representing 70.12%. The influenza vaccination rate was 20.96%. Multivariable logistic regression analysis showed that age (71-<81 years, OR=1.607, 95%CI: 1.041-2.479; ≥81 years, OR=1.719, 95%CI: 1.040-2.842), educational level (middle school/technical secondary school, OR=0.616, 95%CI: 0.416-0.911), medical expense payment (employee medical insurance, OR=6.531, 95%CI: 2.030-21.010; resident medical insurance, OR=3.385, 95%CI: 1.095-10.466; public expense, OR=4.828, 95%CI: 1.700-13.712), vaccination willingness (yes, OR=6.237, 95%CI: 3.277-11.871), influenza vaccination history (yes, OR=14.600, 95%CI: 8.733-24.408) and vaccine literacy (medium and above, OR=2.412, 95%CI: 1.636-3.555) were associated with influenza vaccination among the elderly. Conclusion The influenza vaccination rate among the elderly was relatively low, and was mainly affected by age, educational level, medical expense payment, vaccination willingness, influenza vaccination history and vaccine literacy.

Booster vaccinations are highly recommended in combating the SARS-CoV-2 Omicron variant and its subvariants. However, the optimal booster vaccination strategies and related immune mechanisms with different prior vaccinations are under-revealed. In this study, we systematically evaluated the immune responses in mice and hamsters with different prime-boost regimens before their protective efficacies against Omicron were detected. We found that boosting with Ad5-nCoV, S_WT-2P or S_Omicron-6P induced significantly higher levels of neutralization activities against Omicron variants than CoronaVac and ZF2001 by eliciting stronger germinal center (GC) responses. Specifically, S_Omicron-6P induced even stronger antibody responses against Omicron variants in CoronaVac and Ad5-nCoV-primed animals than non-Omicron-specific vaccines but with limited differences as compared to Ad5-nCoV and S_WT-2P. In addition, boosting with a specific vaccine has the potential to remodel the existing immune profiles. These findings indicated that adenovirus-vectored vaccines and mRNA vaccines would be more effective than other types of vaccines as booster shots in combating Omicron infections. Moreover, the protective efficacies of the vaccines in booster vaccinations are highly related to GC reactions in secondary lymphatic organs. In summary, these findings provide timely important information on prime-boost regimens and future vaccine design.

Objective To investigate the effect of obstructive sleep apnea syndrome(OSAS)on nocturnal ambulatory blood pressure monitoring results in older adults without cardiovascular or cerebrovascular diseases,and to identify factors causing fluctuations in nocturnal blood pressure in older adults with OSAS.Methods A total of 169 older adult OSAS patients with no history of cardiovascular or cerebrovascular diseases were enrolled.According to their severity of OSAS,the participants were divided into 4 groups,including a normal OSAS group,a mild OSAS group,a moderate OSAS group,and a severe OSAS group.The baseline characteristics of the 4 groups were compared to identify differences.The relationship between polysomnography parameters and nocturnal ambulatory blood pressure monitoring results and the factors causing nocturnal blood pressure fluctuations in older adults with OSAS were further analyzed.Results The nocturnal blood pressure fluctuation(NBPF)index of the normal OSAS group,the mild OSAS group,the moderate OSAS group,and the severe OSAS group were 1.89±1.58,3.35±5.40,3.90±6.40,and 16.60±27.70,respectively,indicating that the NBPF index gradually increased with the increasing severity of OSAS(P＜0.05).According to findings from the partial correlation analysis,the NBPF index was positively correlated with apnea-hypopnea index(AHI),micro-awakening index(MAI),percentage of cumulative time with oxygen saturation under 90％in the total sleep time(TS90％),oxygen desaturation index(ODI),and the longest apnea time(LAT)(P＜0.05),and negatively correlated with the lowest oxygen saturation(LSpO2)and sleep quality index(SQI)(P＜0.05).The mean nocturnal systolic and diastolic blood pressures were positively correlated with AHI,ODI,and TS90％(P＜0.05).A multi-factor regression analysis showed that every time ODI increased by 1 unit,the NBPF index increased by 0.26 units(β=0.26;95％CI,0.03-0.50;P=0.030),and every time TS90％increased by 1 unit,the NBPF index increased by 26.78 units(β=26.78;95％CI,2.47-51.08;P=0.031).Conclusion In older adult OSAS patients without cardiovascular or cerebrovascular disease,fluctuations in blood pressure at night become more pronounced with increasing disease severity.ODI and TS90％are important factors that affect nocturnal blood pressure fluctuations.

Objective To evaluate the long-term effects of orthokeratology(ortho-k)lenses with different back optical zone diameters(BOZD)on the quality of vision in myopic children.Methods We conducted an exploratory analysis based on a prospective,randomized,double-blind clinical trial,focusing on the parameters related to visual quality.A total of 66 myopic children aged 8 to 12 years were enrolled and randomly assigned to either a 6-mm BOZD ortho-k lens group(the 6 mm group)or a 5-mm BOZD ortho-k lens group(the 5 mm group).The participants were followed up at baseline,and at 1 day,1 week,and 1,3,6,9,and 12 months after lens wearing.Visual quality measurements included uncorrected visual acuity(VA),best corrected VA,contrast sensitivity(CS),high-order aberrations(HOA),modulation transfer function(MTF),Strayer ratio(SR),and visual quality questionnaire.Results A total of 63 children(33 children in the 6 mm group and 30 children in the 5 mm group)completed the study.There were no significant differences in baseline data between the two groups(P>0.05).There were no significant differences in subjective uncorrected VA or best corrected VA between the two groups at any follow-up visit(P>0.05).After wearing the lenses for 3 months,the CS at high spatial frequency(18 cpd)in the 5 mm group was lower than that in the 6 mm group(P=0.015).However,at 12 months,no significant differences in the CS were found between the two groups(P>0.05).The ocular and corneal total HOA,spherical aberration,and coma aberration in both groups increased after wearing the lenses,and the HOA in the 5 mm group was higher than that in the 6 mm group(all P<0.05).After wearing the lenses for 3 months,the MTF and SR values in the 5 mm group were lower than those in the 6 mm group(P<0.05).At 12 months,there was no significant difference between the two groups(P>0.05).The vision-quality-related questionnaire scores showed no significant differences between the two groups(P>0.05).Conclusion In myopic children,wearing ortho-k lenses with different BOZD results in improved subjective satisfaction,with no difference in subjective visual quality.However,objective visual quality declined in both groups,with a greater impact observed in the 5 mm group.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

OBJECTIVE: To evaluate the effect of biodegradable magnesium alloy materials in promoting tendon-bone healing during rotator cuff tear repair and to investigate their potential underlying biological mechanisms. METHODS: Forty-eight 8-week-old Sprague Dawley rats were taken and randomly divided into groups A, B, and C. Rotator cuff tear models were created and repaired using magnesium alloy sutures in group A and Vicryl Plus 4-0 absorbable sutures in group B, while only subcutaneous incisions and sutures were performed in group C. Organ samples of groups A and B were taken for HE staining at 1 and 2 weeks after operation to evaluate the safety of magnesium alloy, and specimens from the supraspinatus tendon and proximal humerus were harvested at 2, 4, 8, and 12 weeks after operation. The specimens were observed macroscopically at 4 and 12 weeks after operation. Biomechanical tests were performed at 4, 8, and 12 weeks to test the ultimate load and stiffness of the healing sites in groups A and B. At 2, 4, and 12 weeks, the specimens were subjected to the following tests: Micro-CT to evaluate the formation of bone tunnels in groups A and B, HE staining and Masson staining to observe the regeneration of fibrocartilage at the tendon-bone interface after decalcification and sectioning, and Goldner trichrome staining to evaluate the calcification. Immunohistochemical staining was performed to detect the expressions of angiogenic factors, including vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2), as well as osteogenic factors at the tendon-bone interface. Additionally, immunofluorescence staining was used to examine the expressions of Arginase 1 and Integrin beta-2 to assess M1 and M2 macrophage polarization at the tendon-bone interface. The role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in tendon-bone healing was further analyzed using real-time fluorescence quantitative PCR. RESULTS: Analysis of visceral sections revealed that magnesium ions released during the degradation of magnesium alloys did not cause significant toxic effects on organs such as the heart, liver, spleen, lungs, and kidneys, indicating good biosafety. Histological analysis further demonstrated that fibrocartilage regeneration at the tendon-bone interface in group A occurred earlier, and the amount of fibrocartilage was significantly greater compared to group B, suggesting a positive effect of magnesium alloy material on tendon-bone interface repair. Additionally, Micro-CT analysis results revealed that bone tunnel formation occurred more rapidly in group A compared to group B, further supporting the beneficial effect of magnesium alloy on bone healing. Biomechanical testing showed that the ultimate load in group A was consistently higher than in group B, and the stiffness of group A was also greater than that of group B at 4 weeks, indicating stronger tissue-carrying capacity following tendon-bone interface repair and highlighting the potential of magnesium alloy in enhancing tendon-bone healing. Immunohistochemical staining results indicated that the expressions of VEGF and BMP-2 were significantly upregulated during the early stages of healing, suggesting that magnesium alloy effectively promoted angiogenesis and bone formation, thereby accelerating the tendon-bone healing process. Immunofluorescence staining further revealed that magnesium ions exerted significant anti-inflammatory effects by regulating macrophage polarization, promoting their shift toward the M2 phenotype. Real-time fluorescence quantitative PCR results demonstrated that magnesium ions could facilitate tendon-bone healing by modulating the PI3K/AKT signaling pathway. CONCLUSION Biodegradable magnesium alloy material accelerated fibrocartilage regeneration and calcification at the tendon-bone interface in rat rotator cuff tear repair by regulating the PI3K/AKT signaling pathway, thereby significantly enhancing tendon-bone healing.
Animals ; Rotator Cuff Injuries/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Wound Healing/drug effects* ; Alloys/pharmacology* ; Rats ; Proto-Oncogene Proteins c-akt/metabolism* ; Rotator Cuff/metabolism* ; Macrophages/metabolism* ; Magnesium/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Biocompatible Materials ; Bone Morphogenetic Protein 2/metabolism*