Central nervous system diseases (CNSDs) refer to a range of disorders resulting from structural or functional impairments of the brain and spinal cord, including stroke, Alzheimer’s disease (AD), Parkinson’s disease, spinal cord injury (SCI), and brain tumors. As a leading cause of disability and the second leading cause of death worldwide, CNSDs involve complex pathological mechanisms that profoundly affect patients’ physical and mental health as well as their quality of life. Therefore, identifying potential therapeutic targets and developing targeted intervention strategies for the prevention and treatment of CNSDs is of great significance. Recent studies have revealed that lactate can transmit energy between cells via the “lactate shuttle” mechanism and act as an endogenous signaling molecule, exerting diverse biological functions in CNSDs. Lactylation, a novel type of post-translational modification that uses lactate and lysine residues as substrates, plays a critical role in regulating gene transcription, immune responses, and cellular metabolism under both physiological and pathological conditions. Studies have confirmed that lactate participates in the onset and progression of CNSDs through both lactate metabolism and lactylation. In AD, lactate promotes Aβ plaque formation and impairs synaptic plasticity and cognitive function. Lactylation contributes to AD pathogenesis by regulating Aβ accumulation, Tau protein phosphorylation, neuroinflammation, pyroptosis, and ferroptosis. In ischemic stroke (IS), lactate suppresses neuroinflammation and alleviates ischemic injury. Lactylation is involved in the regulation of neuroinflammation, endothelial cell apoptosis, and neuronal ferroptosis, contributing to IS progression. In SCI, lactate promotes the phenotypic transition of astrocytes from the A1 to the A2 type, thereby mitigating neural injury. Lactylation alleviates neurological dysfunction by modulating neuroinflammation, axonal regeneration, mitochondrial function, and microglial proliferation. In glioblastoma (GBM), lactate promotes M2 polarization of microglia, facilitating tumor cell growth and dissemination. Lactylation further accelerates GBM progression by enhancing tumor cell migration, proliferation, immune evasion, and drug resistance. These findings suggest that lactate may serve as a potential therapeutic target for the prevention and treatment of CNSDs. However, its precise role in CNSDs remains unclear, and the specific mechanisms by which lactate metabolism and lactylation influence disease progression warrant further investigation. Moreover, studies have confirmed that exercise, as a key non-pharmacological intervention, holds great promise in the prevention, treatment, and rehabilitation of CNSDs. Specifically, exercise can regulate lactate metabolism and lactylation, which in turn suppresses neuroinflammation, enhances synaptic plasticity, promotes neurogenesis and angiogenesis, improves mitochondrial function in the hippocampus, and facilitates the release of neuroprotective factors, ultimately contributing to the improvement of CNSDs. This review summarizes the roles of lactate metabolism and lactylation in CNSDs, as well as the potential mechanisms by which exercise regulates lactate metabolism and lactylation to improve CNSDs, providing a theoretical basis for the benefits of exercise on brain health.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

OBJECTIVE: To assess the efficacy and safety of Bushen Huoxue Formula (BSHXF) for the treatment of discogenic low-back pain (DLBP). METHODS: This was a parallel, double-blind, randomized, clinical trial performed between May 2019 and June 2020. Seventy patients were assigned by computerized random number table to the treatment group (lumbar traction and BSHXF, 35 cases) or the control group (lumbar traction and placebo, 35 cases). The patients received intervention for 3 weeks. Assessment was conducted before treatment and at week 1, 2, 3 during treatment. Primary outcome was the self-reported score of Oswestry Disability Index (ODI). Secondary outcomes included Visual Analog Scale (VAS), clinical efficacy rate by minimal clinically important difference (MCID) as well as lumbar tenderness, muscle tone and lumbar spine mobility. Adverse reactions were recorded. Follow-up was performed at 1 and 3 months after the end of treatment. RESULTS: In the treatment group, ODI score was significantly decreased compared with baseline (P<0.05) and the control group at 2- and 3- week treatment. Similarly, VAS score decreased compared with the baseline (P<0.05) and was lower than that in the control group at 2- and 3- week treatment (P<0.05). The clinical efficacy rate of the treatment group was higher than that of the control group after treatment [32.35% (11/34) vs. 3.13% (1/32), P<0.05). Moreover, the tenderness, and muscle tone, as well as the back extension and left flexion in lumbar spine mobility in the treatment group at 3-week treatment were significantly improved compared with the control group (P<0.05). Follow-up showed that at 1-month after treatment, the treatment group had better outcomes than the control group with regard to a total score of ODI and VAS scores, as well as clinical efficacy rate (all P<0.05). Moreover, VAS score was still significantly lower than the control group at 3-month follow-up (P<0.05). No adverse reactions were reported during the study. CONCLUSION BSXHF combined with lumbar traction can significantly improve the clinical symptoms including pain intensity, functionality, muscle tone, and lumbar spine mobility in DLBP patients. (Registration No. ChiCTR1900027777).
Humans ; Intervertebral Disc Degeneration/therapy* ; Low Back Pain/drug therapy* ; Lumbar Vertebrae ; Pain Measurement ; Treatment Outcome

Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD. Methods: Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD. Results: From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74–9.09%) with an odds ratio of 1.88 (95% CI, 1.23–2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD. Conclusions This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Betacoronavirus ; Consensus ; Coronavirus Infections ; complications ; epidemiology ; prevention & control ; Epidemics ; Humans ; Minimally Invasive Surgical Procedures ; Musculoskeletal Diseases ; complications ; therapy ; Pandemics ; prevention & control ; Pneumonia, Viral ; complications ; epidemiology ; prevention & control

Objective To understand infection status of human immunodeficiency virus (HIV) and analyze the influencing factors among men who have sex with men (MSM) in Guangzhou. Methods Men who have sex with men (MSM) were recruited from 2014 to 2017. Face-to-face questionnaire survey was conducted to collect information of characterisitc and behaviors. Blood samples were used to detect HIV antibodie. Data were analyzed using SPSS 19.0. Results Among 2 419 MSM, 200(8.27%) participants were confirmed positive for HIV. Multivariate Logistic regression analysis showed that with Guangzhou and monthly economic income >0.5 million as reference, non-Guangzhou (OR=1.712, 95% CI: 1.176-2.492，P=0.005) and monthly economic income ≤0.5 million (OR=1.998, 95% CI: 1.409-2.833，P<0.001) were associated with HIV infection among MSM. Diagnosed syphilis (OR=2.461, 95% CI: 1.375-4.405,P=0.002) , undetected syphilis (OR=2.333, 95% CI: 1.635-3.331,P<0.001), anal sex role passive (OR=2.015, 95% CI: 1.244-3.267,P=0.004), both active and passive (OR=2.115, 95% CI: 1.374-3.251,P=0.001), non-using condoms every time during anal sex (OR=1.955, 95% CI: 1.374-2.781,P<0.001), non-fixed anal sex objects (OR=2.150, 95% CI: 1.463-3.160,P<0.001) were major risk factors for HIV infection among MSM. Conclusions The prevalance of HIV infection and high-risk sexual behavior were high among MSM in Guangzhou. It is urgent to expand the scope of HIV testing and advocate safe sexual behaviors among MSM.

Objective To compare the effectiveness of snail control between immersion of molluscicides through tide diversion and mollusciciding by spraying in marshland areas. Methods Immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion and spraying 26% suspension concentrate of metaldehyde and niclosamide alone were employed for snail control in two neighboring snail-breeding marshlands, and snails were surveyed before and after mollusciciding. The mortality of snails and the density of living snails were estimated. Results The density of living snails reduced by 72.19% and 100.00% 1 and 2 years after immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion, and 5.93% and 18.15% 1 and 2 years after spraying 26% suspension concentrate of metaldehyde and niclosamide alone. Conclusion Immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion is significantly superior to spraying 26% suspension concentrate of metaldehyde and niclosamide along for snail control, and implementation of immersion of 26% suspension concentrate of metaldehyde and niclosamide through tide diversion for more than 2 successive years may achieve a higher snail control efficiency.