Bu zhong Yiqi Decoction ameliorates mild cognitive impairment by improving mitochondrial oxidative stress damage via the SIRT3/MnSOD/OGG1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-Zhong-Yi-Qi Decoction(BZYQD) is a traditional formula commonly used in China, known for its effects in tonifying Qi and raising Yang. It can relieve symptoms of cognitive impairment such as forgetfulness and lack of concentration caused by qi deficiency, which is common in aging and debilitating. However, much of the current research on BZYQD has been focused on its impact on the digestive system, leaving its molecular mechanisms in improving cognitive function largely unexplored. AIM OF THE STUDY: Cognitive decline in the aging central nervous system is intrinsically linked to oxidative damage. This study aims to investigate the therapeutic mechanism of BZYQD in treating mild cognitive impairment caused by qi deficiency, particularly through repair of mitochondrial oxidative damage. MATERIALS AND METHODS: A rat model of mild cognitive impairment (MCI) was established by administering reserpine subcutaneously for two weeks, followed by a two-week treatment with BZYQD/GBE. In vitro experiments were conducted to assess the effects of BZYQD on neuronal cells using a H2O2-induced oxidative damage model in PC12 cells. The open field test and the Morris water maze test evaluated the cognitive and learning memory abilities of the rats. HE staining and TEM were employed to observe morphological changes in the hippocampus and its mitochondria. Mitochondrial activity, ATP levels, and cellular viability were measured using assay kits. Protein expression in the SIRT3/MnSOD/OGG1 pathway was analyzed in tissues and cells through western blotting. Levels of 8-OH-dG in mitochondria extracted from tissues and cells were quantified using ELISA. Mitochondrial morphology in PC12 cells was visualized using Mito Red, and mitochondrial membrane potential was assessed using the JC-1 kit. RESULTS: BZYQD treatment significantly improved cognitive decline caused by reserpine in rats, as well as enhanced mitochondrial morphology and function in the hippocampus. Our findings indicate that BZYQD mitigates mtDNA oxidative damage in rats by modulating the SIRT3/MnSOD/OGG1 pathway. In PC12 cells, BZYQD reduced oxidative damage to mitochondria and mtDNA in H2O2-induced conditions and was associated with changes in the SIRT3/MnSOD/OGG1 pathway. CONCLUSION: BZYQD effectively counteracts reserpine-induced mild cognitive impairment and ameliorates mitochondrial oxidative stress damage through the SIRT3/MnSOD/OGG1 pathway.

Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis.

Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.

The Efficacy and Safety of Celecoxib in Addition to Standard Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35-0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08-1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725-0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI = 1.03-1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09-1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.

Photoredox-Induced Functionalization of Alkenes for the Synthesis of Substituted Imidazolines and Oxazolidines.

A one-pot, three-component cascade reaction combining photoredox catalyzed radical addition and formal [3 + 2] annulation was developed. With this approach, highly concise syntheses of imidazoline and oxazolidine derivatives have been achieved. The advantages of this transformation are good to excellent yields, mild reaction conditions, operational simplicity, and easy accessibility of raw materials.

[Comparison of the curative effect between over-elbow splint and traditional small splint fixation in the treatment of comminuted Colles fracture].

OBJECTIVE: To analyze the clinical efficacy of over-elbow small splint fixation for the treatment of comminuted Colles fractures. METHODS: From October 2013 to October 2015, 52 patients with comminuted Colles fracture were divided into two groups (the traditional splint fixation group and the over-elbow small splint fixation group) according to the treatment strategy. There were 26 patients in the over-elbow small splint fixation group including 7 males and 19 females with an average age of (64.615±11.475) years old ranging from 38 to 85 years old, and 26 patients in the traditional splint fixation group including 9 males and 17 females with an average age of (65.269±13.162) years old ranging 36 to 91 years old, respectively. In the over-elbow small splint fixation group, 3 cases were type A3 fractures, 9 cases were type C1, 7 cases were type C2 and 7 cases were type C3;in the traditional splint fixation group, 4 cases were type A3, 8 cases were type C1, 9 cases were type C2 and 5 cases were type C3. After manipulative reduction, the fractures in traditional splint fixation group were fixed with traditional small splint, and the fractures in over-elbow small splint fixation group were added with over-elbow right angle splint for the first three weeks, then continued fixing like the control group until clinical cicatrization. All patients in both groups were regularly taken X-ray examination and changed dressings to obtain the clinical healing. Patients were guided to do functional exercise after splints were taken off. The therapeutic effects were evaluated according to modified Green and O'Brein score system after 8 weeks' functional exercise. RESULTS: All patients got clinical healing without severe complications in both groups. The shortened length of radius in traditional splint fixation group was more than that in over-elbow small splint fixation group (5.923±1.978) mm VS (2.962±1.248) mm(P<0.05). There was no significant difference in radial incline between two groups. There was a higher wrist score in over-elbow small splint fixation group compared with traditional splint fixation group 89.615±11.482 vs 80.385±13.485(P<0.05). CONCLUSIONS: Over-elbow small splint fixation is better than traditional splint fixation for the treatment of comminuted Colles fracture because of reliable clinical result and excellent wrist functional recovery.

[Case-control study on small splint fixation with trapezoid pad and plaster slab fixation for the treatment of comminuted Colles fracture].

OBJECTIVE: To compare the clinical efficacy of trapezoid pad coordinate with small splint fixation treatment with plaster slab fixation treatment for comminuted Colles fracture. METHODS: From October 2010 to March 2012,80 outpatients with comminuted Colles fracture were divided into two groups. There were 40 patients in trapezoid pad splint fixation treatment group and 40 patients in pipe type plaster control group. There were 13 males and 27 females in trapezoid pad splint fixation treatment group,with an average age of (62.1 +/- 19.2) years old. And there were 15 males and 25 females in pipe type plaster control group,with an average age of (60.2 +/- 19.5) years old. After treated with manipulative reduction,the fractures were fixed with pipe plaster in the control group, and were fixed with trapezoid pad joint by small splint in the treatment group. The patients in both groups were regularly taken X-ray recheck and changed dressings to obtain the clinical healing. Patients were guided to do functional exercise after splints were taken off. The therapeutic effects were evaluated according to Gartland-Werlley wrist score when splints taken off and after 2 months. RESULTS: According to wrist score, the average scores in the treatment group were (8.1 +/- 2.8) when splints taken off and (5.3 +/- 4.5) after 2 months. And the average scores in the control group were (10.3 +/- 2.6) when splints taken off and (8.4 +/- 5.8) after 2 months. The score in the treatment group was higher than that of control group. The average shortened lengths of radius were (4.8 + 1.7) mm in the treatment group and (8.2 +/- 2.1) mm in the control group. The shortened length of control group was larger than that of treatment group. CONCLUSION: Trapezoid pad coordinated with small splint fixation is better than traditional pipe type plaster for treating comminuted Colles fracture.

[To compare and research the clinical effect of treating the comminute distal radius fractures by refining splintage].

OBJECTIVE: To treat the comminute distal radius fractures by improved splint, and obersve the curative effect and compare the radiology with the traditional splint. METHODS: Ninety-two patients with distal radius comminute fracture were randomly divided into two groups. There were 38 males and 54 females. The average age was 63 years old ranging from 23 to 82. Acording to AO classification on the distal fracture of the radius, there were 15 cases of A3, 40 cases of C1, 26 cases of C2 and 11 cases of C3. After all patients were treated by manipulative reduction, 46 cases of the treatment group were fixed supra-carpometacarpal joints by improved splint and trapezoid pad, the other 46 cases of control group were treated with the traditional spilint. Both groups were regularly taken X-ray recheck and changed dressings to obtain the clinical cicatrization. Patients were guided to do functional exercise after splints were taken off. Six weeks later all patients were evaluated the curative and radiologic effect according to Gartland-Werlley wrist score and Lidstrom grade respectively. RESULTS: According to wrist score,there were 13 cases on excellent, 34 cases on fine and 9 cases on normal in treatment group, which average score was (4.0 +/- 2.6) and the percent of wrist functional fitness was 80.6%. There were 9 cases on excellen, 19 cases on fine and 18 cases on normal in control group, which average score was (6.0 +/- 4.2) and the percent of wrist grad and 4 cases on the third grade in treatment group. There were 22 cases on the first grade, 16 cases on the second grad and 8 cases on the third grade in control group. CONCLUSION: The outcome of improved splint was better than that of traditional splint on the function and radiology for treating the comminute distal radius fracture.