The Role of Neuromodulation and Potential Mechanism in Regulating Heterotopic Ossification.

Heterotopic ossification (HO) is a pathological process characterized by the aberrant formation of bone in muscles and soft tissues. It is commonly triggered by traumatic brain injury, spinal cord injury, and burns. Despite a wide range of evidence underscoring the significance of neurogenic signals in proper bone remodeling, a clear understanding of HO induced by nerve injury remains rudimentary. Recent studies suggest that injury to the nervous system can activate various signaling pathways, such as TGF-ß, leading to neurogenic HO through the release of neurotrophins. These pathophysiological changes lay a robust groundwork for the prevention and treatment of HO. In this review, we collected evidence to elucidate the mechanisms underlying the pathogenesis of HO related to nerve injury, aiming to enhance our understanding of how neurological repair processes can culminate in HO.

Association between Cardiometabolic Index and Cognitive Function: A Cross-Sectional Study in a Diabetic-Based Population.

INTRODUCTION: Diabetes is a significant risk factor for cognitive impairment. Therefore, early identification of cognitive impairment in diabetic patients is particularly important. The aim of this study was to assess the relationship between Cardiometabolic index (CMI) and cognitive function in a diabetic population. METHODS: A cross-sectional study was conducted by collecting information from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Multiple linear regression models were used to investigate the correlation between CMI and low cognitive function in a diabetic population. Threshold effects analysis and fitted smoothing curves were used to describe the nonlinear links. Interaction tests and subgroup analyses were also performed. RESULTS: A total of 1,050 people participated in this study, including 561 men and 489 women. In the fully corrected model, CMI was positively associated with low cognitive performance as assessed by CERAD Word List Learning Test (CERAD W-L), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST) (OR = 1.37 [1.14, 1.72], p = 7.4 × 10-3), (OR = 1.21 [1.04, 1.51], p = 1.26 × 10-2), and (OR = 1.27 [1.08, 1.63], p = 2.53 × 10-2). Our study found that diabetic patients with higher CMI were at greater risk of developing low cognitive function. The effect of the subgroups on the positive association of CMI with cognitive impairment was not significant. A non-linear association between low cognitive performance and CMI was determined by CERAD W-L, AFT, and DSST (log-likelihood ratio <5 × 10-2). In addition, our also study found that CMI was a better predictor of cognitive impairment in diabetes than weight-adjusted waist index (WWI). CONCLUSION: Increased CMI is associated with an increased risk of cognitive impairment in people with diabetes. CMI can be used as a new anthropometric measure for predicting cognitive impairment in diabetes, with stronger predictive power than WWI.

Ferroptosis: Latest evidence and perspectives on plant-derived natural active compounds mitigating doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is a chemotherapy drug widely used in clinical settings, acting as a first-line treatment for various malignant tumors. However, its use is greatly limited by the cardiotoxicity it induces, including doxorubicin-induced cardiomyopathy (DIC). The mechanisms behind DIC are not fully understood, but its potential biological mechanisms are thought to include oxidative stress, inflammation, energy metabolism disorders, mitochondrial damage, autophagy, apoptosis, and ferroptosis. Recent studies have shown that cardiac injury induced by DOX is closely related to ferroptosis. Due to their high efficacy, availability, and low side effects, natural medicine treatments hold strong clinical potential. Currently, natural medicines have been shown to mitigate DOX-induced ferroptosis and ease DIC through various functions such as antioxidation, iron ion homeostasis correction, lipid metabolism regulation, and mitochondrial function improvement. Therefore, this review summarizes the mechanisms of ferroptosis in DIC and the regulation by natural plant products, with the expectation of providing a reference for future research and development of inhibitors targeting ferroptosis in DIC. This review explores the mechanisms of ferroptosis in doxorubicin-induced cardiomyopathy (DIC) and summarizes how natural plant products can alleviate DIC by inhibiting ferroptosis through reducing oxidative stress, correcting iron ion homeostasis, regulating lipid metabolism, and improving mitochondrial function.

Modulation of atherosclerosis-related signaling pathways by Chinese herbal extracts: Recent evidence and perspectives.

Atherosclerotic cardiovascular disease remains a preeminent cause of morbidity and mortality globally. The onset of atherosclerosis underpins the emergence of ischemic cardiovascular diseases, including coronary heart disease (CHD). Its pathogenesis entails multiple factors such as inflammation, oxidative stress, apoptosis, vascular endothelial damage, foam cell formation, and platelet activation. Furthermore, it triggers the activation of diverse signaling pathways including Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NF-E2-related factor 2/antioxidant response element (Nrf2/ARE), the Notch signaling pathway, peroxisome proliferator-activated receptor (PPAR), nucleotide oligo-structural domain-like receptor thermoprotein structural domain-associated protein 3 (NLRP3), silencing information regulator 2-associated enzyme 1 (Sirt1), nuclear transcription factor-κB (NF-κB), Circular RNA (Circ RNA), MicroRNA (mi RNA), Transforming growth factor-ß (TGF-ß), and Janus kinase-signal transducer and activator of transcription (JAK/STAT). Over recent decades, therapeutic approaches for atherosclerosis have been dominated by the utilization of high-intensity statins to reduce lipid levels, despite significant adverse effects. Consequently, there is a growing interest in the development of safer and more efficacious drugs and therapeutic modalities. Traditional Chinese medicine (TCM) offers a vital strategy for the prevention and treatment of cardiovascular diseases. Numerous studies have detailed the mechanisms through which TCM active ingredients modulate signaling molecules and influence the atherosclerotic process. This article reviews the signaling pathways implicated in the pathogenesis of atherosclerosis and the advancements in research on TCM extracts for prevention and treatment, drawing on original articles from various databases including Google Scholar, Medline, CNKI, Scopus, and Pubmed. The objective is to furnish a reference for the clinical management of cardiovascular diseases.

Editing homologous copies of an essential gene affords crop resistance against two cosmopolitan necrotrophic pathogens.

Sclerotinia sclerotiorum and Botrytis cinerea are typical necrotrophic pathogens that can attack more than 700 and 3000 plant species, respectively, and cause huge economic losses across numerous crops. In particular, the absence of resistant cultivars makes the stem rot because of S. sclerotiorum the major threat of rapeseed (Brassica napus) worldwide along with Botrytis. Previously, we identified an effector-like protein (SsSSVP1) from S. sclerotiorum and a homologue of SsSSVP1 on B. cinerea genome and found that SsSSVP1 could interact with BnQCR8 of rapeseed, a subunit of the cytochrome b-c1 complex. In this study, we found that BnQCR8 has eight homologous copies in rapeseed cultivar Westar and reduced the copy number of BnQCR8 using CRISPR/Cas9 to improve rapeseed resistance against S. sclerotiorum. Mutants with one or more copies of BnQCR8 edited showed strong resistance against S. sclerotiorum and B. cinerea. BnQCR8-edited mutants did not show significant difference from Westar in terms of respiration and agronomic traits tested, including the plant shape, flowering time, silique size, seed number, thousand seed weight and seed oil content. These traits make it possible to use these mutants directly for commercial production. Our study highlights a common gene for breeding of rapeseed to unravel the key hindrance of rapeseed production caused by S. sclerotiorum and B. cinerea. In contrast to previously established methodologies, our findings provide a novel strategy to develop crops with high resistance against multiple pathogens by editing only a single gene that encodes the common target of pathogen effectors.

l-Cysteine suppresses hypoxia-ischemia injury in neonatal mice by reducing glial activation, promoting autophagic flux and mediating synaptic modification via H2S formation.

We previously reported that l-Cysteine, an H2S donor, significantly alleviated brain injury after hypoxia-ischemic (HI) injury in neonatal mice. However, the mechanisms underlying this neuroprotective effect of l-Cysteine against HI insult remain unknown. In the present study, we tested the hypothesis that the protective effects of l-Cysteine are associated with glial responses and autophagy, and l-Cysteine attenuates synaptic injury as well as behavioral deficits resulting from HI. Consistent with our previous findings, we found that treatment with l-Cysteine after HI reduced early brain injury, improved behavioral deficits and synaptic damage, effects which were associated with an up-regulation of synaptophysin and postsynaptic density protein 95 expression in the lesioned cortex. l-Cysteine attenuated the accumulation of CD11b+/CD45high cells, activation of microglia and astrocytes and diminished HI-induced increases in reactive oxygen species and malondialdehyde within the lesioned cortex. In addition, l-Cysteine increased microtubule associated protein 1 light chain 3-II and Beclin1 expression, decreased p62 expression and phosphor-mammalian target of rapamycin and phosphor-signal transducer and activator of transcription 3. Further support for a critical role of l-Cysteine was revealed from results demonstrating that treatment with an inhibitor of the H2S-producing enzyme, amino-oxyacetic acid, reversed the beneficial effects of l-Cysteine described above. These results demonstrate that l-Cysteine effectively alleviates HI injury and improves behavioral outcomes by inhibiting reactive glial responses and synaptic damage and an accompanying triggering of autophagic flux. Accordingly, l-Cysteine may provide a new a therapeutic approach for the treatment of HI via the formation of H2S.

Efficacy of five different traditional Chinese medicine injections in acute upper respiratory tract infection in children: a network meta-analysis and systematic review.

Background: Acute upper respiratory tract infection (AURI) includes infections caused by a variety of pathogens and is one of the most common diseases in children. Traditional Chinese medicine (TCM) injections are widely used for treating AURI in clinical practice, but their efficacy is unclear because of the lack of clear evidence. In this study, a network meta-analysis (NMA) was used to evaluate the efficacy and safety of TCM injections in the treatment of AURI and to provide a reference for clinical treatment. Methods: Eight databases were searched, namely, PubMed, Embase, the Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), the Wanfang database, and the Chinese Scientific Journal database (VIP). The search time period was from 1 January 2013 to 1 November 2023. Randomized controlled trials of herbal injections for treating AURI were searched. The Cochrane Risk of Bias 2.0 tool was used to assess the quality of these studies. Review Manager 5.4 and Stata 15.0 were used for the NMA. Results: A total of 81 papers involving 11,736 patients were included. These involved five different TCM injections, namely, Xiyanping injection (XYPI), Qingkailing injection (QKLI), Reduning injection (RDNI), Yanhuning injection (YHNI), and Tanreqing injection (TRQI). QKLI was most effective in alleviating symptoms of fever and improving overall clinical effectiveness. TRQI was most effective in relieving cough symptoms. YHNI was most effective in alleviating sore throat, runny nose, and nasal congestion. The overall incidence of adverse effects of these herbal injections in the treatment of AURI was lower, and their safety profiles were better. Conclusions: The herbal injections combined with ribavirin improved clinical outcomes, and were superior to ribavirin injection alone in alleviating clinical symptoms such as fever, cough, sore throat, runny nose, and nasal congestion, and have favorable safety profiles. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023484099, CRD42023484099.

Effects of modified Danggui Sini Decoction as adjuvant therapy for angina pectoris in coronary heart disease: a systematic review and meta-analysis based on randomised controlled trials.

Introduction: This systematic review evaluates the efficacy of the Chinese herbal formula modified Danggui Sini Decoction as an adjunctive treatment for angina pectoris in patients with coronary heart disease. Methods: We conducted a comprehensive search for randomized controlled trials that investigated the effects of modified Danggui Sini Decoction in combination with conventional Western medication on angina pectoris in coronary artery disease, published up to July 2023 across eight databases, including China Knowledge International Literature screening and data extraction were performed by two researchers following predefined inclusion and exclusion criteria. The quality of included studies was assessed using the Cochrane Handbook version 5.1, and meta-analysis was executed via RevMan 5.4 software. Results: Thirteen studies encompassing 1,232 participants were incorporated. The meta-analysis revealed that combining modified Danggui Sini Decoction with conventional Western medication significantly enhanced overall clinical efficacy, reduced the duration of angina attacks, decreased the Chinese medicine syndrome score, improved inflammatory markers and cardiac function, lowered serum NT-proBNP levels, and elevated the Seattle Angina Questionnaire scores compared to the control group. Conclusion: Modified Danggui Sini Decoction, when used alongside conventional Western medications, shows promise in treating coronary artery disease patients with angina pectoris and may serve as a beneficial adjunctive therapy in clinical settings. Nonetheless, due to the limited quantity and quality of the included studies, further high-caliber research is essential to substantiate these findings. Systematic Review Registration: https://inplasy.com/? s=202390078, identifier INPLASY 202390078.

Therapeutic Role of Chinese Medicine Targeting Nrf2/HO-1 Signaling Pathway in Myocardial Ischemia/Reperfusion Injury.

Acute myocardial infarction (AMI), characterized by high incidence and mortality rates, poses a significant public health threat. Reperfusion therapy, though the preferred treatment for AMI, often exacerbates cardiac damage, leading to myocardial ischemia/reperfusion injury (MI/RI). Consequently, the development of strategies to reduce MI/RI is an urgent priority in cardiovascular therapy. Chinese medicine, recognized for its multi-component, multi-pathway, and multi-target capabilities, provides a novel approach for alleviating MI/RI. A key area of interest is the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. This pathway is instrumental in regulating inflammatory responses, oxidative stress, apoptosis, endoplasmic reticulum stress, and ferroptosis in MI/RI. This paper presents a comprehensive overview of the Nrf2/HO-1 signaling pathway's structure and its influence on MI/RI. Additionally, it reviews the latest research on leveraging Chinese medicine to modulate the Nrf2/HO-1 pathway in MI/RI treatment.

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging.

Osteoarthritis (OA), a chronic degenerative joint disease, is highly prevalent among the aging population, and often leads to joint pain, disability, and a diminished quality of life. Although considerable research has been conducted, the precise molecular mechanisms propelling OA pathogenesis continue to be elusive, thereby impeding the development of effective therapeutics. Notably, recent studies have revealed subchondral bone lesions precede cartilage degeneration in the early stage of OA. This development is marked by escalated osteoclast-mediated bone resorption, subsequent imbalances in bone metabolism, accelerated bone turnover, and a decrease in bone volume, thereby contributing significantly to the pathological changes. While the role of aging hallmarks in OA has been extensively elucidated from the perspective of chondrocytes, their connection with osteoclasts is not yet fully understood. There is compelling evidence to suggest that age-related abnormalities such as epigenetic alterations, proteostasis network disruption, cellular senescence, and mitochondrial dysfunction, can stimulate osteoclast activity. This review intends to systematically discuss how aging hallmarks contribute to OA pathogenesis, placing particular emphasis on the age-induced shifts in osteoclast activity. It also aims to stimulate future studies probing into the pathological mechanisms and therapeutic approaches targeting osteoclasts in OA during aging.

A multifunctional nanogel encapsulating layered double hydroxide for enhanced osteoarthritis treatment via protection of chondrocytes and ECM.

Osteoarthritis (OA) is characterized by progressive and irreversible damage to the articular cartilage and a consecutive inflammatory response. However, the majority of clinical drugs for OA treatment only alleviate symptoms without addressing the fundamental pathology. To mitigate this issue, we developed an inflammation-responsive carrier and encapsulated bioactive material, namely, LDH@TAGel. The LDH@TAGel was designed with anti-inflammatory and antioxidative abilities, aiming to directly address the pathology of cartilage damage. In particular, LDH was confirmed to restore the ECM secretion function of damaged chondrocytes and attenuate the expression of catabolic matrix metalloproteinases (Mmps). While TAGel showed antioxidant properties by scavenging ROS directly. In vitro evaluation revealed that the LDH@TAGel could protect chondrocytes from inflammation-induced oxidative stress and apoptosis via the Nrf2/Keap1 system and Pi3k-Akt pathway. In vivo experiments demonstrated that the LDH@TAGel could alleviated the degeneration and degradation of cartilage induced by anterior cruciate ligament transection (ACLT). The OARSI scores indicating OA severity decreased significantly after three weeks of intervention. Moreover, the IVIS image revealed that LDH@TAGel enhances the controlled release of LDH in a manner that can be customized according to the severity of OA, allowing adaptive, precise treatment. In summary, this novel design effectively alleviates the underlying pathological causes of OA-related cartilage damage and has emerged as a promising biomaterial for adaptive, cause-targeted OA therapies.

The Dynamic Changes of Brassica napus Seed Microbiota across the Entire Seed Life in the Field.

The seed microbiota is an important component given by nature to plants, protecting seeds from damage by other organisms and abiotic stress. However, little is known about the dynamic changes and potential functions of the seed microbiota during seed development. In this study, we investigated the composition and potential functions of the seed microbiota of rapeseed (Brassica napus). A total of 2496 amplicon sequence variants (ASVs) belonging to 504 genera in 25 phyla were identified, and the seed microbiota of all sampling stages were divided into three groups. The microbiota of flower buds, young pods, and seeds at 20 days after flowering (daf) formed the first group; that of seeds at 30 daf, 40 daf and 50 daf formed the second group; that of mature seeds and parental seeds were clustered into the third group. The functions of seed microbiota were identified by using PICRUSt2, and it was found that the substance metabolism of seed microbiota was correlated with those of the seeds. Finally, sixty-one core ASVs, including several potential human pathogens, were identified, and a member of the seed core microbiota, Sphingomonas endophytica, was isolated from seeds and found to promote seedling growth and enhance resistance against Sclerotinia sclerotiorum, a major pathogen in rapeseed. Our findings provide a novel perspective for understanding the composition and functions of microbiota during seed development and may enhance the efficiency of mining beneficial seed microbes.

Differential proteomic analysis of caveolin-1 KO cells reveals Sh2b3 and Clec12b as novel interaction partners of caveolin-1 and Capns1 as a potential mediator of caveolin-1-induced apoptosis.

Caveolin-1 (Cav1) is a small scaffolding protein involved in a variety of cellular functions, including cell signaling, lipid transport and membrane traffic. The objective of this study was to use comparative proteomics to identify differentially expressed proteins in Cav1 knockout (KO) mouse embryonic fibroblasts. These deregulated proteins were then analyzed using systems biology tools to gain insight into the local network properties and to identify the interaction partners of Cav1. We identified five proteins that were up-regulated and ten proteins that were down-regulated in Cav1 KO cells, suggesting that the local network behaves as a complex system. Protein interaction network analysis revealed two proteins, Sh2b3 and Clec12b, as novel interaction partners of Cav1. Functional annotation showed apoptosis signaling as the most significant pathway. To validate this functional annotation, Cav1 KO cells showed more than 1.5-fold increase in caspase-3 activity over wild type cells upon apoptotic stimulation. We also found that calpain small subunit 1 is up-regulated in Cav1 KO cells and directly influences the cell response to apoptotic stimuli. Moreover, Capns1 was reduced in Cav1 KO cells following re-expression of Cav1, and suppression of Capns1 expression in Cav1 KO cells significantly inhibited the cells to apoptotic stimuli, as measured by caspase 3 activity. In conclusion, our results suggest that Sh2b3 and Clec12b functionally interact with Cav1 and that calpain small subunit 1 may mediate Cav1-induced apoptosis.

AMPK Signalling Pathway: A Potential Strategy for the Treatment of Heart Failure with Chinese Medicine.

Heart failure (HF) is a complex clinical syndrome that represents the advanced stage of cardiovascular disease, characterized by systolic and diastolic dysfunction of the heart. Despite continuous updates in HF treatment drugs, the morbidity and mortality rates remain high, necessitating ongoing exploration for new therapeutic targets. Adenosine monophosphate-activated protein kinase (AMPK) is the serine/threonine protein kinase which responds to adenosine monophosphate (AMP) levels.Activation of AMPK shifts cellular metabolic patterns from synthesis to catabolism, enhancing energy metabolism in pathological conditions such as inflammation, ischemia, obesity, and aging. Numerous studies have identified AMPK as a vital target for HF treatment, with herbal monomers/extracts and compounds affecting key signaling factors including rapamycin targeting protein (mTOR), silencing regulator protein 1 (SIRT1), nuclear transcription factor E2-related factor 2 (Nrf2), and nuclear transcription factor-κB (NF-κB) through regulation of the AMPK signaling pathway.This modulation can achieve the effects of improving metabolism, autophagy, reducing oxidative stress and inflammatory response in the treatment of heart failure, with the advantages of multi-targeting, comprehensive action and low toxicity.The modulation of the AMPK pathway by Traditional Chinese Medicine (TCM) has emerged as a crucial research direction for the prevention and treatment of HF, but a systematic summary and generalization in this field is lacking. This article provides an overview of the composition, regulation, and mechanism of the AMPK signaling pathway's influence on HF, as well as a summary of current research on the regulation of the AMPK pathway by TCM for HF prevention and treatment. The aim is to serve as a reference for the diagnosis and treatment of HF using TCM and the development of new drugs.

CT-based radiomics nomogram may predict who can benefit from adaptive radiotherapy in patients with local advanced-NSCLC patients.

BACKGROUND: Although adaptive radiotherapy (ART) has many advantages, ART is not universal in the clinical appliance due to the consumption of a lot of labor, and economic burden. It is necessary to explore a CT stimulation-based radiomics model for screening who can get more benefits from ART in locally advanced non-small cell lung cancer (NSCLC) patients. METHOD: 183 cases of NSCLC patients receiving concurrent chemoradiotherapy with an adaptive approach were enrolled as a primary cohort, while 28 cases from another hospital served as an independent external validation cohort. Tumor regression assessment was conducted based on GTV reduction (Criteria A) or according to RECIST Version 1.1(Criteria B). The radiomics features were extracted by the "PyRadiomics" package and further screened by the LASSO method. Then, logistic regression was used to establish the model. Bootstrap and external validation were applied to verify the stability of the model. The receiver operating characteristic (ROC) curve was delineated to assess the predictive efficacy of the radiomics model. Dose-volume histograms were quantitatively compared between the initial and composite ART plans. Clinical endpoints included overall survival (OS) and progression-free survival (PFS). RESULT: There were no significant differences in clinical features between tumor regression-resistant (RR) and tumor regression-sensitivity (RS) groups. The AUC values of the Criteria A model and Criteria B model were 0.767 and 0.771, respectively. Bootstrapping validation and external validation confirmed the stability of models. In all patients, there was a significant benefit of ART in the lung, heart, cord, and esophagus compared to non-ART, particularly in RS patients. Furthermore, PFS and OS from ART were significantly longer in RS as defined by Criterion B than in RR patients with the same ART application. CONCLUSION: CT-based radiomics can screen out the patients who can gain more benefits from ART, which contribute to guiding and popularizing the application of ART strategy in the clinic within economic benefits and feasibility.

Adjuvant Chinese Medicine for the Treatment of Type 2 Diabetes Mellitus Combined with Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of a Randomised Controlled Trial.

Mild cognitive impairment has a high prevalence in the type 2 diabetic population. Adjuvant therapy with Chinese herbal medicine can effectively improve the clinical symptoms of patients with T2DM combined with MCI. The aim of this study was to systematically evaluate the efficacy and safety of Chinese herbal adjunctive therapy in the treatment of diabetes mellitus combined with cognitive impairment. Information was analysed using the China Knowledge Network, Vip Database, Wanfang Database, China Biomedical Literature Database, PubMed, EMbase, Web of Science, and MedLine Database. The total clinical efficiency, blood glucose, blood lipids, Simple Mental-State Examination Scale (MMSE), Montreal Cognitive Assessment Scale (MoCA), Traditional Chinese Medicine Symptom Score (TCMSS), and incidence of adverse reactions were recorded. The methodological quality of the included studies was evaluated using the application of the Cochrane Collaboration Network Risk Bias Assessment Tool, and meta-analysis was performed using RevMan 5.4 software. Adjuvant treatment with Chinese herbal medicine was effective in improving the clinical outcomes (OR = 5.33, 95% CI (3.62, 7.84), p < 0.00001) and cognitive function by comparing with the control group: MMSE (MD = 1.56, 95% CI (1.29, 1.84), p < 0.00001) and MoCA (MD = 2.77, 95% CI (1.81, 3.73), p < 0.0001); lowered blood glucose: fasting blood glucose (FBG) (MD = −0.27, 95% CI (−0.42, −0.12), p = 0.0006), 2 hPG (MD = −0.28, 95% CI (−0.45, −0.10), p = 0.002), and glycated haemoglobin (HbA1c) (MD = −0.26, 95% CI (−0.39, −0.14), p < 0.001); and improved lipids: total cholesterol (TC) (MD = −0.51, 95% CI (−0.82, −0.21), p = 0.001), triglycerides (TGs) (MD = −0.46, 95% CI −0.46, 95% CI (−0.80, −0.11), p = 0.009), low-density lipoprotein (LDL-C) (MD = −0.28, 95% CI (−0.55, −0.02), p = 0.04), high-density lipoprotein (HDL-C) (MD = 0.17, 95% CI (0.07, 0.28), p = 0.001), reduced TCMSS (MD = −1.84, 95% CI (−2.58, −1.10), p < 0.0001), and incidence of adverse events (OR = 0.46, 95% CI (0.24, 0.88), p = 0.02). In conclusion, through the available evidence, herbal adjuvant therapy for T2DM combined with MCI was observed to be effective and did not significantly increase the adverse effects. Due to the limitation of the number and quality of the included studies, the abovementioned results need to be validated by further high-quality studies.

Efficacy and Safety of Vitamin D Adjuvant Therapy for Ulcerative Colitis: A Meta-Analysis.

Objective: To examine the clinical efficacy and safety of Vitamin D in the treatment of ulcerative colitis in a systematic manner. Methods: RCT studies on Vitamin D in the treatment of ulcerative colitis were searched from CNKI, Wanfang Data, PubMed, Cochrane Library, and Web of Science databases. RevMan 5.4 software was used for analysis. Results: 10 articles were included, including 1077 patients. Meta-analysis results showed that when clinical efficacy was used as the outcome index, the clinical efficacy of the oral vitamin group was higher than that of the conventional treatment group (OR = 4.07, 95% CI 2.64-6.27), and the difference was statistically significant (Z = 6.38, P < 0.00001). When the Mayo risk score was used as the outcome index, the difference was statistically significant, indicating that oral Vitamin D significantly reduced the Mayo risk score (MD: -0.41, CI = (-0.47, -0.34), Z = 13.09, P < 0.00001). Using the intestinal mucosal barrier as the outcome index, the results showed that (1) the MDA group (MD = -0.75, 95% CI (-0.96~-0.53), P < 0.00001), (2) the DAO group (MD = -1.17, 95% CI (-1.39-0.95), P < 0.00001), and the Vitamin D group could effectively improve intestinal mucosal barrier function after sensitivity analysis (MD = -1.00, 95% CI (-1.08-0.92), P < 0.00001). When inflammatory factors were used as outcome indicators, IL-6, TNF-α, and CRP groups had statistical significance (MD = -4.50, 95% CI (-5.13-3.87), P < 0.00001); MD = -7.27, 95% CI (18.96-5.58), P < 0.00001; and MD = -1.49, 95% CI (-1.76~-1.23), P < 0.00001, respectively). When the incidence of adverse reactions was used as the outcome indicator (OR = 0.73, 95% CI (0.34-1.32), P = 0.23), there was no significant difference between the two groups. Conclusion: Vitamin D combined with mesalazine is effective in the treatment of ulcerative colitis, by improving the Mayo score and intestinal barrier function, and reducing inflammatory factors, with no significant safety difference. However, due to the quality of the included researches, more RCT researches needed to provide sufficient evidence to support clinical application. This study is registered with INPLASY 202250044.

Intestinal Flora Balance Therapy Based on Probiotic Support Improves Cognitive Function and Symptoms in Patients with Alzheimer's Disease: A Systematic Review and Meta-analysis.

Objective: The clinical value of intestinal flora balance therapy based on probiotic support in improving cognitive function and symptoms of patients with Alzheimer's disease was to systematically evaluate, so as to provide evidence-based medicine basis for the promotion and use of this therapy. Methods: The randomized controlled trials (RCTs) were searched for the improvement of cognitive function and symptoms of patients with Alzheimer's disease by intestinal flora balance therapy supported mainly by probiotics in PubMed, EMBASE, ScienceDirect, Cochrane Library, China Knowledge Network Database (CNKI), China VIP database, Wanfang database, and China Biomedical Literature Database (CBM) online database (RCT). Data were extracted independently by two researchers, and the literature was assessed for risk of bias according to the Cochrane Handbook 5.1.0 criteria. The data were meta-analyzed using RevMan 5.4 statistical software. Results: Finally, 5 randomized controlled trials were included, with a total sample size of 386 cases. The results of meta-analysis showed that Chi2 = 13.14, df = 2, P = 0.001, and I 2 = 85% showed significant heterogeneity in the inclusion of the study data. Probiotic-supported intestinal microflora balance therapy improves cognitive function in patients with Alzheimer's disease. Through meta-analysis of transient memory scores, it is concluded that intestinal flora balance therapy based on probiotic support can improve transient memory in patients with Alzheimer's disease. Meta-analysis of ADAS-COG score showed that intestinal flora balance therapy supported by probiotics could improve the cognitive function of patients with Alzheimer's disease. The ADL score was analyzed by meta, and the heterogeneity test result was Chi2 = 0.79, df = 1, P = 0.37 > 0.05, and I 2 = 0%, indicating that the intestinal flora balance therapy supported by probiotics can improve the ability of daily living of patients with Alzheimer's disease. Conclusion: Intestinal flora balance therapy based on probiotic support can effectively improve cognitive function, instantaneous memory, and ability of daily life in patients with Alzheimer's disease. However, more studies and long-term follow-up studies with higher methodological quality are needed to further verify.

A Practical Mathematic Method to Predict and Manage Hypocalcemia After Parathyroidectomy and Thyroidectomy.

OBJECTIVE: Prediction and early intervention for hypocalcemia following parathyroidectomy and total thyroidectomy can decrease hospital cost and prevent severe hypocalcemia-related complications. This study aims to predict the severity of hypocalcemia after parathyroidectomy or thyroidectomy and to stratify patients into groups with different levels of risk for developing severe hypocalcemia, so that higher risk patients may be monitored more closely and receive earlier interventions. METHODS: This was a retrospective cohort study of 100 patients with primary hyperparathyroidism who underwent parathyroidectomy as the primary treatment modality at a tertiary care hospital. Clinical information, including demographic information, perioperative PTH and calcium levels, vitamin D levels, weight of the pathologic glands removed, gland pathology, and re-admission rates, were retrieved. Statistical analysis was performed to analyze the association between collected variables and percentage of calcium drop following parathyroidectomy with statistical significant set at P-values <0.05. RESULTS: Age, sex, and vitamin D level provided very minimal information to quantify risks of postoperative hypocalcemia. The percentage of decrease from preoperative PTH level to the lowest PTH level after the removal of the abnormal gland(s) is the most significant predicting factor for the severity of postoperative hypocalcemia. There is a mathematic regressional correlation between them. A formula was generated to quantify this linear relationship between them, and the nadir calcium can be calculated as Canadir=Capreop*[1-0.35*(PTHpreop-PTHintraop)2PTHpreop2], where Canadir = the lowest postoperative calcium level, and PTHintraop = PTH level 15 minutes after removal of the abnormal gland, with the value of R2 > 0.7. The formula has been tested primarily in our patient population with good reliability. CONCLUSIONS: The highest preoperative, lowest postoperative, and change in PTH level can help us reliably calculate the trend of postoperative calcium level. Decision to pursue early interventions can be made based on the calculated result from the formula we obtained.