Integrated untargeted and targeted testicular metabolomics to reveal the regulated mechanism of Gushudan on the hypothalamic-pituitary-gonadal axis of kidney-yang-deficiency-syndrome rats.

Modern studies have shown that neuroendocrine disorders caused by the dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis are one of the important pathogenetic mechanisms of kidney-yang-deficiency-syndrome (KYDS). The preventive effect of Gushudan on KYDS has been reported, but its regulatory mechanisms on the HPG axis have not been elucidated. In this study, we developed an integrated untargeted and targeted metabolomics analysis strategy to investigate the regulatory mechanism of Gushudan on the HPG axis in rats with KYDS. In untargeted metabolomics, we screened 14 potential biomarkers such as glycine, lysine, and glycerol that were significantly associated with the HPG axis. To explore the effect of changes in the levels of potential biomarkers on KYDS, all of them were quantified in targeted metabolomics. With the quantitative results, correlations between potential biomarkers and testosterone, a functional indicator of the HPG axis, were explored. The results showed that oxidative stress, inflammatory response, and energy depletion, induced by metabolic disorders in rats, were responsible for the decrease in testosterone levels. Gushudan improves metabolic disorders and restores testosterone levels, thus restoring HPG axis dysfunction. This finding elucidates the special metabolic characteristics of KYDS and the therapeutic mechanism of Gushudan from a new perspective.

Brief discussion of the differences in the acupoint location between Meridians and Acupoints and Acupuncture and Moxibustion. / æµ è®®ã€Šç»ç»œè §ç©´å­¦ã€‹å’Œã€Šé’ˆç¸å­¦ã€‹"十四五"规划教材经穴定位差异.

There are the differences in the location of some acupoints between textbooks Meridians and Acupoints and Acupuncture and Moxibustion. Both of the textbooks are in the category of the "14th Five-Year Plan". The differences in acupoint location have brought some confusion for students, full-time teachers and researchers in the field of traditional Chinese medicine. In the paper, based on GB/T 12346-2021： Nomenclature and Location of Meridian Points, published in2021, and in reference with GB/T 12346-2006： Nomenclature and Location of Acupuncture Points, published in 2006, the discrepancy in the acupoint location was systematically collated in the aspects of the expression style and layout, text expression and potential difference of location between these two textbooks, published by China Press of Traditional Chinese Medicine, People's Medical Publishing House and China Science Publishing. Based on the historical evolution and the academic controversy of acupoint positioning, the reasons of the differences in acupoint location were analyzed, the potential influences on the teaching, examination, competition and research of Chinese medicine acupuncture were explored, and the suggestions for solution were proposed.

Acute ischemic stroke in tuberculous meningitis.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

[Effects of α1-antitrypsin on motor function in mice with immature brain white matter injury]. / α1-æŠ—èƒ°è›‹ç™½é ¶å¯¹æœªæˆç†Ÿè„‘ç™½è´¨æŸä¼¤å°é¼ è¿åŠ¨åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To investigate the effects of α1-antitrypsin (AAT) on motor function in adult mice with immature brain white matter injury. METHODS: Five-day-old C57BL/6J mice were randomly assigned to the sham surgery group (n=27), hypoxia-ischemia (HI) + saline group (n=27), and HI+AAT group (n=27). The HI white matter injury mouse model was established using HI methods. The HI+AAT group received intraperitoneal injections of AAT (50 mg/kg) 24 hours before HI, immediately after HI, and 72 hours after HI; the HI+saline group received intraperitoneal injections of the same volume of saline at the corresponding time points. Brain T2-weighted magnetic resonance imaging scans were performed at 7 and 55 days after modeling. At 2 months of age, adult mice were evaluated for static, dynamic, and coordination parameters using the Catwalk gait analysis system. RESULTS: Compared to the sham surgery group, mice with HI injury showed high signal intensity on brain T2-weighted magnetic resonance imaging at 7 days after modeling, indicating significant white matter injury. The white matter injury persisted at 55 days after modeling. In comparison to the sham surgery group, the HI+saline group exhibited decreased paw print area, maximum contact area, average pressure, maximum pressure, paw print width, average velocity, body velocity, stride length, swing speed, percentage of gait pattern AA, and percentage of inter-limb coordination (left hind paw → left front paw) (P<0.05). The HI+saline group showed increased inter-paw distance, percentage of gait pattern AB, and percentage of phase lag (left front paw → left hind paw) compared to the sham surgery group (P<0.05). In comparison to the HI+saline group, the HI+AAT group showed increased average velocity, body velocity, stride length, and swing speed (right front paw) (P<0.05). CONCLUSIONS: The mice with immature brain white matter injury may exhibit significant motor dysfunction in adulthood, while the use of AAT can improve some aspects of their motor function.

Integrative analysis identifies cancer cell-intrinsic RARRES1 as a predictor of prognosis and immune response in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and limited treatment options. Although immune checkpoint inhibitors (ICIs) have been proven to improve outcomes in TNBC patients, the potential mechanisms and markers that determine the therapeutic response to ICIs remains uncertain. Revealing the relationship and interaction between cancer cells and tumor microenvironment (TME) could be helpful in predicting treatment efficacy and developing novel therapeutic agents. By analyzing single-cell RNA sequencing dataset, we comprehensively profiled cell types and subpopulations as well as identified their signatures in the TME of TNBC. We also proposed a method for quantitatively assessment of the TME immune profile and provided a framework for identifying cancer cell-intrinsic features associated with TME through integrated analysis. Using integrative analyses, RARRES1 was identified as a TME-associated gene, whose expression was positively correlated with prognosis and response to ICIs in TNBC. In conclusion, this study characterized the heterogeneity of cellular components in TME of TNBC patients, and brought new insights into the relationship between cancer cells and TME. In addition, RARRES1 was identified as a potential predictor of prognosis and response to ICIs in TNBC.

Concurrent Ammonia Synthesis and Alcohol Oxidation Boosted by Glutathione-Capped Quantum Dots under Visible Light.

Mother nature accomplishes efficient ammonia synthesis via cascade N2 oxidation by lightning strikes followed with enzyme-catalyzed nitrogen oxyanion (NOx -, x = 2,3) reduction. The protein environment of enzymatic centers for NOx --to-NH4 + process greatly inspires the design of glutathione-capped (GSH) quantum dots (QDs) for ammonia synthesis under visible light (440 nm) in tandem with plasma-enabled N2 oxidation. Mechanistic studies reveal that GSH induces positive shift of surface charge to strengthen the interaction between NOx - and QDs. Upon visible light irradiation of QDs, the balanced and rapid hole and electron transfer furnish GS·radicals for 2e-/2H+ alcohol oxidation and H·for 8e-/10H+ NO3 --to-NH4 + reduction simultaneously. For the first time, mmol-scale ammonia synthesis is realized with apparent quantum yields of 5.45% ± 0.64%, and gram-scale synthesis of value-added acetophenone and NH4Cl proceeds with 1:4 stoichiometry and stability, demonstrating promising multielectron and multiproton ammonia synthesis efficiency and sustainability with nature-inspired artificial photocatalysts.

Physical exercise frequency and cognition: a multicenter cross-sectional cohort study.

Background and aims: Dementia imposes a heavy burden on society and families, therefore, effective drug treatments, exploring and preventing factors associated with dementia, are paramount. To provide reference points for the best frequency of physical exercise (physical exercise), we investigated the association between frequency of PE and cognition in Chinese old adults. Methods: 16,181 Chinese participants aged 65 years or older were included in this study. Associations between PE and cognition were estimated multivariate logistic and linear regression analyses. Associations were further investigated across dementia subtypes (Alzheimer dementia, vascular dementia, and other types of dementia). Subgroup analyses were performed in different age groups, in populations with and without stroke, and those with and without hypertension. Results: PE associated with dementia after adjusting for full covariates (OR: 0.5414, 95% CI: 0.4536-0.6491, p < 0.001). Exercise performed at ≥3 times/week associated with lower risk of dementia (OR: 0.4794-0.6619, all p value <0.001). PE was associated with improved cognition (ß: 12851, p < 0.001), and any PE frequency contributed to cognitive improvement (p values for exercise performed ≥1 time/week were <0.001). Similar conclusions were identified when we repeated analyses in different dementia subtypes and age groups. Subgroup analyses suggested that the cognition of individuals without hypertension also benefitted from exercising 1-2 times/week (OR: 0.6168, 95% CI: 0.4379-0.8668, p = 0.005). Conclusion: The best exercise frequency is exercising ≥3 times/week for individuals from different dementia subtypes and age groups. While for those without hypertension, PE at 1-2 times /week is also beneficial.

Association between traditional Chinese Medicine and osteoarthritis outcome: A 5-year matched cohort study.

Objective: The aim of this study was to investigate the relationship between Traditional Chinese medicine (TCM) and pain reduction, hospital readmission, and joint replacement in patients with osteoarthritis (OA). Chinese herbal medicine (CHM) prescription patterns were further analyzed to confirm the association with prognosis and quality of life in OA patients. Methods: We retrospectively followed 3,850 hospitalized patients with osteoarthritis between January 2018 and December 2022 using the hospital's HIS system. Propensity score matching (PSM) was used for data matching. Cox's proportional risk model was used to assess the impact of various factors on the outcomes of patients with OA, including pain worsening, readmission, and joint replacement. The Kaplan-Meier survival curve was applied to determine the impact of TCM intervention time on patient outcomes. Data mining methods including association rules, cluster analysis, and random walks have been used to assess the efficacy of TCM. Results: The utilization rate of TCM in OA patients was 67.01% (2,511/3,747). After PSM matching, 1,228 TCM non-user patients and 1,228 TCM user patients were eventually included. The outcomes of pain worsening, re-admission rate, and joint replacement rate of the TCM non-user group were observably higher than those of the TCM user group with OA (p < 0.05). Based on the Cox proportional risk model, TCM is an independent protective factor. Compared with non-TCM users, TCM users had 58.4% lower rates of pain, 51.1% lower rates of re-admission, and 42% lower rates of joint replacement. In addition, patients in the high-exposure subgroup (TCM＞24 months) had a markedly lower risk of outcome events than those in the low-exposure subgroup (TCM ≤24 months). Data mining methods have shown that TCM therapy can significantly improve immune-inflammatory indices, VAS scores, and SF-36 scale scores in OA patients. Conclusion: s TCM acts as a protective factor to improve the prognosis of patients with OA, and the benefits of long-term use of herbal medicines are even greater.

Integrated UHPLC-MS untargeted metabolomics and gut microbe metabolism pathway-targeted metabolomics to reveal the prevention mechanism of Gushudan on kidney-yang-deficiency-syndrome rats.

Gushudan (GSD) was a traditional Chinese prescription with the remarkable effect of kidney-tonifying and bone-strengthening. However, the potential prevention mechanisms of the GSD on kidney-yang-deficiency-syndrome (KYDS) and its regulation on gut microbe metabolism still need to be further systematically investigated. This study established untargeted urinary metabolomics based on RP/HILIC-UHPLC-Q-Orbitrap HRMS and combined with multivariate statistical analysis to discover differential metabolites and key metabolic pathways. And the gut microbe metabolism pathway-targeted metabolomic based on HILIC-UHPLC-MS/MS was developed and validated to simultaneously determine 15 gut microbe-mediated metabolites in urine samples from the control group (CON), KYDS model group (MOD), GSD-treatment group (GSD) and positive group (POS). The results showed that a total of 36 differential metabolites were discovered in untargeted metabolomics. These differential metabolites included proline, cytosine, butyric acid and nicotinic acid, which were primarily involved in the gut microbe metabolism, amino acid metabolism, energy metabolism and nucleotide metabolism. And GSD played a role in preventing KYDS by regulating these metabolic pathways. The targeted metabolomics found that the levels of 10 gut microbe-mediated metabolites had significant differences in different groups. Among them, compared with the CON group, the levels of lysine, tryptophan, phenylacetylglycine and hippuric acid were increased in the MOD group, while the levels of threonine, leucine, dimethylamine, trimethylamine, succinic acid and butyric acid were decreased, which verified the disorders of gut microbe metabolism in the KYDS rats and GSD had a significant regulatory effect on this disorder. As well as by comparing analysis, it was found that the experimental results were consistent with previous metabolomics and microbiomics of fecal samples. Therefore, this integrated strategy of untargeted and targeted metabolomics not only elucidated the potential prevention mechanism of GSD on KYDS, but also provided a scientific basis for GSD preventing KYDS via the "gut-kidney" axis.

Novel approach of ultrasound-guided lateral recess block for a patient with lateral recess stenosis: A case report.

BACKGROUND: Ultrasound guide technology, which can provide real-time visualization of the needle tip and tissues and avoid many adverse events, is widely used in minimally invasive therapy. However, the studies on ultrasound-guided Lateral recess block (LRB) are limited, this is probably because there is no recognized standard method for ultrasound scanning. This study aimed to evaluate the effect of ultrasound-guided LRB in patients with lateral recess stenosis (LRS). CASE SUMMARY: A 65-year-old patient complained of low back pain accompanied occasionally by pain and numbness in the left lower limb. Physical examination showed tenderness on the spinous process and paraspinal muscles from L1 to S1, extensor hallucis longus and tibialis anterior weakness (muscle strength: 4-), and a positive straight leg raising test in the left lower limb (60°). Magnetic resonance imaging showed L4-L5 disc degeneration with left LRS and nerve root entrapment. Subsequently, the patient was diagnosed with LRS. This patient was treated with a novel ultrasound-guided LRB approach. The patient's symptoms significantly improved without any complications at 1 wk postoperatively and at the 3-month follow-up. CONCLUSION: This is the first report on the LRS treatment with ultrasound-guided LRB from the contralateral spinous process along the inner side of the articular process by out-plane technique. Further studies are expected to investigate the efficacy and safety of ultrasound-guided LRB for patients with LRS.

Mechanical circulatory support for cardiogenic shock: a network meta-analysis of randomized controlled trials and propensity score-matched studies.

PURPOSE: Cardiogenic shock is associated with high mortality. In refractory shock, it is unclear if mechanical circulatory support (MCS) devices improve survival. We conducted a network meta-analysis to determine which MCS devices confers greatest benefit. METHODS: We searched MEDLINE, Embase, and Scopus databases through 27 August 2023 for relevant randomized controlled trials (RCTs) and propensity score-matched studies (PSMs). We conducted frequentist network meta-analysis, investigating mortality (either 30 days or in-hospital) as the primary outcome. We assessed risk of bias (Cochrane risk of bias 2.0 tool/Newcastle-Ottawa Scale) and as sensitivity analysis reconstructed survival data from published survival curves for a one-stage unadjusted individual patient data (IPD) meta-analysis using a stratified Cox model. RESULTS: We included 38 studies (48,749 patients), mostly reporting on patients with Society for Cardiovascular Angiography and Intervention shock stages C-E cardiogenic shock. Compared with no MCS, extracorporeal membrane oxygenation with intra-aortic balloon pump (ECMO-IABP; network odds ratio [OR]: 0.54, 95% confidence interval (CI): 0.33-0.86, moderate certainty) was associated with lower mortality. There were no differences in mortality between ECMO, IABP, microaxial ventricular assist device (mVAD), ECMO-mVAD, centrifugal VAD, or mVAD-IABP and no MCS (all very low certainty). Our one-stage IPD survival meta-analysis based on the stratified Cox model found only ECMO-IABP was associated with lower mortality (hazard ratio, HR, 0.55, 95% CI 0.46-0.66). CONCLUSION: In patients with cardiogenic shock, ECMO-IABP may reduce mortality, while other MCS devices did not reduce mortality. However, this must be interpreted within the context of inter-study heterogeneity and limited certainty of evidence.

Exome-Wide Sequencing Study Identified Genetic Variants Associated With Sarcopenic Obesity.

Sarcopenic obesity (SO) is an age-related disease characterized by the coexistence of excessive adiposity and low muscle mass or function. Although obesity and sarcopenia are heritable conditions, the genetic determinants of SO have not been fully understood. We conducted a large-scale exome-wide association analysis of SO in a sequenced sample of 2 887 cases and 113 284 controls and an imputed sample of 4 003 cases and 161 990 controls in the UK Biobank cohort. Single-variant association analysis identified one locus 1q41 (lead SNP rs1417066, LYPLAL1-AS1, odds ratio [OR] = 1.15, 95% confidence interval [CI] = [1.11-1.19], p = 1.75 × 10-14) that was significantly associated with SO at the exome-wide significance level (p < 1 × 10-8). Colocalization analysis in the Genotype-Tissue Expression expression quantitative trait locus database showed that LYPLAL1-AS1 was colocalized with SO in multiple musculoskeletal-related tissues. Gene-based burden test of rare loss-of-function variants identified 5 genes at the gene-wise significance level (p < 4.3 × 10-6): PDE3B (OR = 2.48, p = 1.10 × 10-6), MYOZ3 (OR = 25.49, p = 1.41 × 10-7), SLC15A3 (OR = 4.75, p = 6.82 × 10-7), RNF130 (OR = 25.83, p = 4.07 × 10-6), and TNK2 (OR = 4.25, p = 8.75 × 10-8). Overall, our study uncovered the genetic effects of both common and rare variants on SO susceptibility, expanded existing knowledge of the genetic architecture of SO, and improved understanding of the genetic mechanisms underlying SO.

The effect of long-term traditional Chinese medicine treatment on extra-articular lesions of rheumatoid arthritis patients based on propensity score matching: A retrospective cohort study.

Objective: To explore the efficacy of long-term traditional Chinese medicine (TCM) treatment on the occurrence of extra-articular lesions in rheumatoid arthritis (RA) patients. Methods: Our retrospective cohort study included patients diagnosed with RA between January 2018 to December 2019. Patients were divided into TCM treatment group and control group according to whether they received TCM treatment for more than three months. Propensity score matching (PSM) was used to balance covariates between groups. The occurrence time of extra-articular lesions, including interstitial lung disease, Sjögren's syndrome, and anemia, was calculated for both groups after PSM. Additionally, clinical indicators that may affect the occurrence of extra-articular lesions in RA were included in Cox multivariate regression analysis to explore prognostic factors related to RA. Results: A total of 883 RA patients were initially included in our study, with 481 in the TCM treatment group and 279 in the control group. TCM treatment improved all clinical indicators of RA patients, and there was a higher degree of support, confidence, and lift between TCM treatment and the improvement of clinical indicators. There was no significant difference in the rate of extra-articular lesions occurrence between the two groups. After PSM, the median occurrence time of interstitial lung disease, Sjögren's syndrome and anemia in the TCM treatment group were 30.767, 21.370 and 31.970 months, respectively. While in the control group, it was 15.911, 14.667 and 11.825 months, respectively. Cox multivariate regression analysis indicated that TCM treatment was a protective factor for the occurrence of extra-articular lesions in RA, while abnormally high level of IgG was an independent factor for interstitial lung disease and C4 was an independent factor for Sjögren's syndrome. Moreover, a longer duration of TCM usage was associated with a later occurrence of extra-articular lesions. Conclusion: Long-term TCM treatment not only positively affects the occurrence time of extra-articular lesions in RA patients, but also helps reduce the risk of extra-articular lesions occurrence. TCM can be applied flexibly throughout the treatment process for RA patients.

Common Markers of Muscle Damage are Associated with Divergent Gene Expression Patterns after Eccentric Contractions.

PURPOSE: Unaccustomed eccentric (ECC) exercise evokes exercise-induced muscle damage (EIMD). Soreness, strength loss and serum creatine kinase (CK) are often used to quantify EIMD severity. However, changes in these markers are not fully understood mechanistically. To test the hypothesis that muscle damage markers are associated with unique molecular processes, we correlated gene expression responses with variation in each marker post-ECC. METHODS: Vastus lateralis biopsies were collected from 35 young men 3-hr post-ECC (10 sets of 10 maximal eccentric contractions; contralateral leg (CON) as control). Maximal isometric strength, soreness, and serum creatine kinase activity were assessed 24 h pre-exercise and every 24 hours for 5 days post-ECC. Strength was also measured 10-minutes post-ECC. Over the five days following ECC, average peak strength loss was 51.5 ± 20%; average soreness increased from 0.9 ± 1.9 on a 100 mm visual analog scale to 39 ± 19; serum CK increased from 160 ± 130 to 1,168 ± 3,430 U/L. Muscle RNA was used to generate gene expression profiles. Partek Genomics Suite correlated peak values of soreness, strength loss and CK post-ECC with gene expression in ECC (relative to paired CON) using Pearson linear correlation (p < 0.05) and repeated measures analysis or variance used to detect influence of ECC. RESULTS: After ECC, 2677 genes correlated with peak soreness; 3333 genes with peak strength loss; and 3077 genes with peak CK. Less than 1% overlap existed across all markers (16/9087). Unique genes included 2346 genes for peak soreness, 3032 genes for peak strength loss, and 2937 genes for peak CK. CONCLUSIONS: The largely unique molecular pathways associated with common indirect markers of EIMD indicates that each marker of "damage" represents unique mechanistic processes.