Alzheimer's disease （AD）， a degenerative disease of the central nervous system， is characterized by progressive degradation of learning， memory， and cognitive functions. Currently， few drugs are available for treating AD， and their effects are limited. Berberine （BBR） is a natural isoquinoline （quaternary ammonium-like） with a wide range of pharmacological effects. Studies have proven that BBR has good potential in the treatment of AD. Specifically， BBR can inhibit the generation， aggregation， and neurotoxicity of amyloid-β and the hyperphosphorylation of Tau protein， promote the clearance of phosphorylated Tau protein， reduce the cholinesterase activity， neuroinflammation， and oxidative stress， regulate neuronal apoptosis， improve the mitochondrial function and glucose and lipid metabolism， suppress the monoamine oxidase activity， and modulate gut microbiota. In addition， researchers have ameliorated the low bioavailability of BBR. Probing into the potential targets is hoped to provide a reference for further research on the prevention and treatment of AD by BBR.

Background Atherosclerotic cardiovascular disease (ASCVD) is a major contributor to the global burden of cardiovascular diseases. However, evidence from meta-analyses on the association between ambient ozone exposure and ASCVD risk remains relatively insufficient. Objective To explore the epidemiological association between ambient ozone exposure and ASCVD, providing scientific evidence for ASCVD prevention and control from the perspective of environmental risk factor management. Methods We systematically searched PubMed, Web of Science, Embase, the Cochrane Library, CNKI, Wanfang Database, CBM, and VIP for published epidemiological studies on the relationship between ambient ozone exposure and ASCVD from January 2007 to December 2023. We performed quality assessment and data extraction of the included studies, and utilized meta-analysis to evaluate the effects of short-term and long-term ozone exposure on different ASCVD outcomes, including mortality and incidence of ischemic heart disease (IHD) and ischemic stroke (IS). Results A total of 24 studies were included based on a set of predetermined eligibility criteria. The meta-analysis results indicated that short-term ozone exposure was associated with an increased risk of ASCVD mortality and incidence. Specifically, short-term ozone exposure was significantly associated with an elevated risk of IHD mortality (combined RR=1.011, 95%CI: 1.008, 1.015; P < 0.05). Additionally, short-term ozone exposure was significantly linked to increased IS mortality (combined RR=1.005, 95%CI: 1.003, 1.008; P < 0.05) and incidence (combined RR=1.015, 95%CI: 1.003, 1.027; P < 0.05). Conclusion Short-term exposure to ambient ozone significantly elevates acute cardiovascular disease risk. However, the epidemiological association between long-term ozone exposure and ASCVD remains inconclusive. Future high-quality cohort studies with refined exposure assessment methods are warranted to elucidate the chronic cardiovascular effects of ozone exposure.

OBJECTIVE: To explore the efficacy differences among different acupuncture frequencies for pain of temporomandibular disorders (TMD). METHODS: A total of 42 patients with TMD pain were randomly divided into a low-frequency group, a medium-frequency group, and a high-frequency group, with 14 patients in each group. All groups received acupuncture treatment at bilateral Hegu (LI4) and Yanglingquan (GB34), as well as ipsilateral Tinggong (SI19), Jiache (ST6), and Xiaguan (ST7), with each session lasting 30 minutes. The low-frequency group received acupuncture once per week, the medium-frequency group received acupuncture twice per week, and the high-frequency group received acupuncture three times per week, for a total duration of four weeks. The graded chronic pain scale (GCPS) score, visual analogue scale (VAS) score, jaw functional limitation scale-20 (JFLS-20) score, and pressure pain threshold (PPT) were assessed in the three groups before and after treatment, as well as at the four-week follow-up after treatment completion. RESULTS: Compared before treatment, GCPS and JFLS-20 scores were significantly decreased in all the groups after treatment (P<0.05), and VAS scores were significantly decreased in the high-frequency and medium-frequency groups (P<0.05), PPT values at different measurement sites were increased significantly in the high-frequency group (P<0.05). After treatment, GCPS, JFLS-20, and VAS scores in the high-frequency group were lower than those in the medium-frequency and low-frequency groups (P<0.05), while some PPT values were higher than the other two groups (P<0.05). At follow-up, GCPS, JFLS-20, and VAS scores remained significantly lower in all the groups compared to baseline (P<0.05), PPT values were increased significantly in the high-frequency and medium-frequency groups (P<0.05), with the high-frequency group showing lower GCPS, JFLS-20, and VAS scores and higher PPT values compared to the other two groups (P<0.05). CONCLUSION Acupuncture three times per week is more effective in reducing TMD pain intensity compared to once or twice per week, and can also alleviate some mandibular functional impairments. The therapeutic effects persist for at least four weeks after treatment completion.
Humans ; Male ; Female ; Adult ; Acupuncture Therapy/methods* ; Temporomandibular Joint Disorders/physiopathology* ; Middle Aged ; Young Adult ; Treatment Outcome ; Acupuncture Points ; Pain Management ; Adolescent ; Pain Measurement

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

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

OBJECTIVE To observe the efficacy and safety of hydromorphone in patient-controlled intravenous analgesia(PCIA)after uvulopalatopharyngoplasty.METHODS A total of 90 patients who received uvulopalatopharyngoplasty in Central Theater General Hospital from January 2022 to June 2023 were selected and divided into three groups(n=30 in each group)by using random number table method.Control group was given sufentanil 2.0 μg/kg,group A was given hydromorphone 0.20 mg/kg and group B was given hydromorphone 0.30 mg/kg.The analgesic parameters of three groups were background infusion rate of 1.2 ml/h,PCA amount of 2 ml,and lock-up time of 10 min.VAS score and Ramsay sedation score at 2 h,6 h,12 h,24 h and 48 h after surgery were recorded,as well as the number of compressions within 48 h after surgery,and the incidence of adverse reactions were analyzed.RESULTS There were no significant differences in intraoperative blood loss,operation time and intraoperative urine volume among the three groups(P>0.05).VAS score in group A and group B at 2 h(2.0±0.3,2.2±0.4),6 h(1.8±0.4,1.9±0.4),12 h(1.8±0.4,1.7±0.4),24 h(1.6±0.3,1.5±0.4)and 48 h(1.1±0.3,1.2±0.4)were significantly lower than those in control group(2.8±0.5,2.3±0.5,2.1±0.4,2.0±0.5,1.7±0.5)(P<0.05),but there was no significant difference between group A and group B(P>0.05).The Ramsay score of group A and group B at 2 h,6 h,12 h,24 h,and 48 h after operation was significantly lower than that of the control group(P<0.05).There was no significant difference in Ramsay score between group A and group B(P>0.05).The total number of compressions and effective number of compressions in group A and group B at 12 h,24 h and 48 h after surgery were lower than those in control group(P<0.05),but there was no significant difference between group A and group B(P>0.05).The incidence of total adverse reactions in group B was higher than that in group A and control group(P<0.05).There was no significant difference in the incidence of total adverse reactions between group A and control group(P<0.05).CONCLUSION Hydromorphone can effectively be used for postoperative self-controlled analgesia in patients with uvulopalatopharyngoplasty,and the efficacy is better than sufentanil,but the dose of 0.20 mg/kg hydromorphone has better safety than that of 0.3 mg/kg hydromorphone.

Objective To observe the alterations in functional complexity of brain regions in autism spectrum disorder(ASD)patients and correlations with the predicted brain age.Methods Open brain resting-state functional MRI(rs-MRI)data of 93 ASD patients and 96 typically developing adolescents(healthy subjects)were downloaded.The functional complexity in brain regions were extracted with self-developed virtual digital brain software,and the alterations in functional complexity of brain regions in ASD patients and correlations with their ages were analyzed.Two networks were prospectively trained with data of 65 ASD patients and 67 healthy subjects as the training set to predict brain age,and the results were evaluated,and the predicting errors were compared using test set,i.e.the other 28 ASD patients and 29 healthy subjects.Results Compared to healthy subjects,on the basis of anatomical automatic labeling(AAL)atlas,ASD patients exhibited significantly reduced functional complexity based on Shannon entropy in the left precuneus,left cuneus and right parahippocampal gyrus.Conversely,functional complexity of ASD patients based on permutation entropy significantly increased in the left cuneus and right cerebellar Crus Ⅱ region.The left hippocampus showed reduced functional complexity based on Pearson correlation coefficient,while the left middle temporal gyrus showed increased functional complexity based on Pearson correlation coefficient.The functional complexity in brain regions of ASD patients were not closely correlated with ages(all|r|＜0.4).According to the trained fully connected network,the predicted brain ages of ASD patients and healthy subjects in test set were all lower than their physiological ages,but no significant difference was found between the prediction errors of ASD patients and healthy subjects(P=0.283).Conclusion Functional complexity changed in some brain region functions in ASD patients.The predicted brain ages of ASD patients based on the obtained fully connected network were on the low side,but not obviously affected by the alterations of functional complexity in brain regions.