ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

Lung transplantation is an important means to treat end-stage lung disease and improve the survival rate and quality of life of patients. However, many postoperative complications seriously affect the prognosis of recipients. Accurate identification of key prognostic factors and construction of individualized and accurate prediction models are of great significance for postoperative prognosis evaluation, treatment strategy formulation and clinical decision-making. In recent years, the clinical prediction model of lung transplantation has gradually changed from traditional statistical methods to machine learning-driven. Compared with traditional models such as Cox regression and Logistic regression, machine learning models such as random forest, support vector machine and artificial neural network have certain advantages in postoperative survival rate prediction, early warning of complications and pulmonary function evaluation. However, their application is also affected by insufficient sample size and poor interpretability of models. Under the condition of small samples, the traditional model still has important value in prediction accuracy. The appropriate prediction model should be selected according to the clinical status of lung transplantation in China, considering the factors such as sample size, variable complexity and model interpretability. In the future, a multi-center, large-sample lung transplantation database should be constructed to further optimize and tap the potential of machine learning algorithms to improve the robustness and clinical applicability of the model.

OBJECTIVE: Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19. This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio (NLPR) with the severity and prognosis of COVID-19, and the effect of XBJ on the prognosis of patients with COVID-19 in different inflammatory states. METHODS: This was a retrospective study conducted at Wuhan Union Hospital in China. COVID-19 patients admitted between November 1, 2022 and February 1, 2023 were included. In predicting prognosis for individuals with COVID-19, new inflammatory indicators were used, and their prognostic value was assessed by using Cox regression models and receiver operating characteristic curves. Furthermore, a calculation was made to determine the cutoff value for NLPR. Relative risk and Cox regression models were used to examine the effects of Xuebijing injection on prognosis in patient cohorts that had been stratified by the NLPR cutoff. RESULTS: This research included 455 participants with COVID-19, with a mean age of 72 years. Several inflammatory indicators were found to be strongly correlated with prognosis, and NLPR shows the greatest predictive power. Patients with NLPR > 3.29 exhibited a mortality rate of 17.3%, which was 6.2 times higher than in patients with NLPR ≤ 3.29. Importantly, providing Xuebijing injection to patients with NLPR > 3.29 was associated with a lower risk of 60-day all-cause mortality. However, there was no discernible improvement in survival among patients with NLPR ≤ 3.29 who received Xuebijing injection. CONCLUSION NLPR is the most reliable inflammatory marker for predicting prognosis among individuals with COVID-19, and can accurately identify individuals who may benefit from Xuebijing injection. Please cite this article as: Liao M, Zhang LT, Bai LJ, Wang RY, Liu Y, Han J, Liu LH, Qi BL. Xuebijing injection reduces COVID-19 patients mortality as influenced by the neutrophil to lymphocyte platelet ratio. J Integr Med. 2025; 23(3): 282-288.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Female ; Retrospective Studies ; Aged ; Neutrophils ; COVID-19 Drug Treatment ; COVID-19/blood* ; Middle Aged ; Prognosis ; Lymphocytes ; Blood Platelets ; Platelet Count ; SARS-CoV-2 ; Aged, 80 and over ; Adult

Objective Low-density lipoprotein cholesterol(LDL-C)is causally associated with atherosclerotic cardiovascular disease(ASCVD).Proprotein convertase subtilisin/kexin type 9(PCSK9)increases the degradation of low-density lipoprotein receptor(LDL-R),thereby promoting lipid accumulation.This study investigated the mechanism of microRNA(miRNA)-125a-5p in regulating PCSK9 transcriptional expression and lipid accumulation through histone deacetylase sirtuin 6(SIRT6)-mediated histone acetylation.Methods RAW264.7 macrophages exposed to oxidized low-density lipoprotein(ox-LDL)were used to establish a macrophage lipid accumulation model.The cells were divided into eight groups:control group(Group A),ox-LDL group(Group B),SIRT6 agonist group(Group C),si-SIRT6 group(Group D),miR-125a-5p mimic group(Group E),miR-125a-5p mimic negative control group(Group F),miR-125a-5p inhibitor group(Group G),and miR-125a-5p inhibitor negative control group(Group H).Oil red O staining was used to verify lipid ac-cumulation in macrophages.Real-time fluorescent quantitative polymerase chain reaction(PCR)was employed to detect the gene expression levels of miR-125a-5p,SIRT6 and PCSK9.Western blotting was used to detect the protein expression levels of SIRT6,histone 3 lysine 9 acetylation(H3K9ac),histone 3(H3),and PCSK9.An LDL-C kit was used to measure cellular LDL-C con-tent.Results Compared with Group A,Group B exhibited increased relative gene expression of miR-125a-5p,decreased relative SIRT6 gene and its protein expression,increased H3K9ac/H3 rati-o,increased relative gene and protein expression of PCSK9,and elevated LDL-C levels,with statis-tically significant differences(P＜0.01).In Group B,a positive correlation was observed between H3K9ac and PCSK9 protein expression(r=0.935 0,P＜0.01),as well as between PCSK9 and LDL-C(r=0.981 3,P＜0.01).Compared with Group B,Group C showed no significant change in miR-125a-5p expression(P＞0.05),but increased relative SIRT6 gene and its protein expres-sion,decreased H3K9ac/H3 ratio,decreased relative gene and protein expression of PCSK9,and reduced LDL-C levels(P＜0.01).In contrast,Group D,compared with Group B,had no signifi-cant change in miR-125a-5p gene expression(P＞0.05),but decreased relative gene and protein expression of SIRT6,increased H3K9ac/H3 ratio,increased relative PCSK9 gene and its protein expression,and elevated LDL-C levels(P＜0.05 or P＜0.01).Group E,compared with Group B,showed increased relative gene expression of miR-125a-5p,decreased relative SIRT6 gene and its protein expression,increased H3K9ac/H3,increased relative PCSK9 gene and its protein ex-pression,and elevated LDL-C levels(P＜0.01).Group G,compared with Group B,had de-creased relative gene expression of miR-125a-5p,increased relative gene and protein expression of SIRT6,decreased H3K9ac/H3 ratio,decreased relative PCSK9 gene and protein expression,and reduced LDL-C levels(P＜0.01).No significant changes were observed in miR-125a-5p,SIRT6,H3K9ac/H3 ratio,PCSK9,or LDL-C levels in Groups F and H compared with Group B(P＞0.05).Conclusion Epigenetics is an important regulatory mechanism in the development of ather-osclerosis(AS).Elevated LDL-C is a significant risk factor for AS,and increased PCSK9 expres-sion exacerbates lipid accumulation.Imbalance in histone acetylation is a novel mechanism involved in PCSK9-mediated lipid accumulation,potentially serving as an early detection marker for lipid me-tabolism disorders.SIRT6 acts as a protective factor by reversibly regulating PCSK9 transcriptional expression,reducing lipid accumulation,and delaying AS progression.MiR-125a-5p,as an up-stream regulatory gene of SIRT6,targets and inhibits SIRT6 transcription,thereby modulating his-tone acetylation,and may serve as a new target for early screening and prevention of dyslipidemia.

Objective:To explore the effects of 4C management mode on rehabilitation and quality of life in patients with acute heart failure(AHF)in cardiovascular intensive care unit(CCU).Methods:This randomized controlled study enrolled 110 patients with AHF admitted in CCU of Guangdong Provincial Hospital of Traditional Chinese Medicine between February 2021 and February 2023.Patients were randomly divided into intervention group(n=55)and control group(n=55).Patients in the control group received routine intervention,while those in the inter-vention group received additional 4C management mode,both groups were intervened for 3 months.The indexes of cardiac function,self-efficacy,exercise tolerance,blood oxygen saturation(SpO2),mental state and quality of life were compared between the two groups.Results:Compared to those in the control group after intervention,patients in the intervention group had significantly lower interventricular septal thickness(IVST)[(9.20±0.10)mm vs.(10.30±0.17)mm,P＜0.001],left ventricular end-systolic volume index(LVESVI)[(35.21±0.74)ml/m2 vs.(39.70±1.09)ml/m2,P＜0.001],left ventricular end-diastolic volume index(LVED VI)[(45.35±0.71)ml/m2 vs.(56.76±1.48)ml/m2,P＜0.001],scores of self-rating anxiety scale(SAS)[(32.10±1.57)points vs.(45.36±1.94)points,P＜0.001],self-rating depression scale(SDS)[(35.03±1.52)points vs.(47.70±2.12)points,P＜0.001]and Minnesota living with heart failure questionnaire(MLHFQ)[(51.27±2.85)points vs.(56.46±3.53)points,P＜0.001],and significantly higher score of general self-efficacy scale(GSES)[(28.71±3.84)points vs.(20.34±1.56)points,P＜0.001],6 min walking distance(6MWD)[(428.53±5.50)m vs.(362.14±6.18)m,P＜0.001]and SpO2[(99.11±0.87)％vs.(94.23±0.73)％,P＜0.001].Conclusion:4C management mode may improve the cardiac function,self-efficacy,mental state and quality of life in patients with acute heart failure in CCU.

Objective:To explore the effects of 4C management mode on rehabilitation and quality of life in patients with acute heart failure(AHF)in cardiovascular intensive care unit(CCU).Methods:This randomized controlled study enrolled 110 patients with AHF admitted in CCU of Guangdong Provincial Hospital of Traditional Chinese Medicine between February 2021 and February 2023.Patients were randomly divided into intervention group(n=55)and control group(n=55).Patients in the control group received routine intervention,while those in the inter-vention group received additional 4C management mode,both groups were intervened for 3 months.The indexes of cardiac function,self-efficacy,exercise tolerance,blood oxygen saturation(SpO2),mental state and quality of life were compared between the two groups.Results:Compared to those in the control group after intervention,patients in the intervention group had significantly lower interventricular septal thickness(IVST)[(9.20±0.10)mm vs.(10.30±0.17)mm,P＜0.001],left ventricular end-systolic volume index(LVESVI)[(35.21±0.74)ml/m2 vs.(39.70±1.09)ml/m2,P＜0.001],left ventricular end-diastolic volume index(LVED VI)[(45.35±0.71)ml/m2 vs.(56.76±1.48)ml/m2,P＜0.001],scores of self-rating anxiety scale(SAS)[(32.10±1.57)points vs.(45.36±1.94)points,P＜0.001],self-rating depression scale(SDS)[(35.03±1.52)points vs.(47.70±2.12)points,P＜0.001]and Minnesota living with heart failure questionnaire(MLHFQ)[(51.27±2.85)points vs.(56.46±3.53)points,P＜0.001],and significantly higher score of general self-efficacy scale(GSES)[(28.71±3.84)points vs.(20.34±1.56)points,P＜0.001],6 min walking distance(6MWD)[(428.53±5.50)m vs.(362.14±6.18)m,P＜0.001]and SpO2[(99.11±0.87)％vs.(94.23±0.73)％,P＜0.001].Conclusion:4C management mode may improve the cardiac function,self-efficacy,mental state and quality of life in patients with acute heart failure in CCU.

Lung transplantation is an important means to treat end-stage lung disease and improve the survival rate and quality of life of patients. However, many postoperative complications seriously affect the prognosis of recipients. Accurate identification of key prognostic factors and construction of individualized and accurate prediction models are of great significance for postoperative prognosis evaluation, treatment strategy formulation and clinical decision-making. In recent years, the clinical prediction model of lung transplantation has gradually changed from traditional statistical methods to machine learning-driven. Compared with traditional models such as Cox regression and Logistic regression, machine learning models such as random forest, support vector machine and artificial neural network have certain advantages in postoperative survival rate prediction, early warning of complications and pulmonary function evaluation. However, their application is also affected by insufficient sample size and poor interpretability of models. Under the condition of small samples, the traditional model still has important value in prediction accuracy. The appropriate prediction model should be selected according to the clinical status of lung transplantation in China, considering the factors such as sample size, variable complexity and model interpretability. In the future, a multi-center, large-sample lung transplantation database should be constructed to further optimize and tap the potential of machine learning algorithms to improve the robustness and clinical applicability of the model.

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Objective:To explore the association between serum 25-hydroxyvitamin D[25(OH)D]and handgrip strength in middle-aged and elderly people in 5 cities of Western China.Methods:Based on the data of a cross-sectional survey conducted in the 5 cities of Western China from February to July 2023,the relevant demographic characteristics of people were collected by questionnaire,handgrip strength was collected by physical examination,and serum 25(OH)D was detected by HPLC-MS/MS.The association between the serum 25(OH)D and handgrip strength was analyzed using Logistic regres-sion and Chi-square test for between-group comparisons models.Results:The prevalence of 25(OH)D deficiency and insufficiency among the middle-aged and elderly people in the 5 cities of Western China was 52.9％and 34.5％,respectively.The people who were older,female,and sampled in winter had lower serum 25(OH)D levels(P＜0.05).The prevalence of loss of handgrip strength among the mid-dle-aged and elderly people was 25.3％.The prevalence of handgrip strength loss was higher in the aged 65-80 participants with 25(OH)D deficiency(45.0％)than in those with 25(OH)D insufficiency(32.6％)and 25(OH)D sufficiency(20.6％).The highest prevalence of loss of handgrip strength was found in the aged 75-80 participants with 25(OH)D deficiency(62.1％),followed by the 25(OH)D insufficient group(11.1％,P＜0.05).The study found that middle-aged and elderly people with 25(OH)D deficiency had a 1.4-fold increased risk of handgrip strength loss compared with those with 25(OH)D sufficiency(OR=2.403,95％CI:1.202-4.804,P=0.013).No significant association was found between 25(OH)D insufficiency and handgrip strength status in the middle-aged and elderly people.For every 5 μg/L increase in total serum 25(OH)D,the risk of handgrip strength loss reduced by 13.1％(OR=0.869,95％CI:0.768-0.982,P=0.025).For every 5 μg/L increase in serum 25(OH)D2,the risk of handgrip strength loss reduced by 24.1％(OR=0.759,95％CI:0.582-0.990,P=0.042).No significant association was found between serum 25(OH)D3 levels and the risk of hand-grip strength loss.The risk of handgrip strength loss in middle-aged and elderly people was reduced by 25.2％for each incremental increase in the total serum 25(OH)D levels(deficient,insufficient and suf-ficient)(OR=0.748,95％CI:0.598-0.936,P=0.011).The risk of handgrip loss was reduced by 40.0％for each incremental increase in serum 25(OH)D levels in the aged 65-80 and aged 65-69 participants,and by 80.0％for each incremental increase in 25(OH)D levels in the aged 75-80 parti-cipants.Conclusion:Serum total 25(OH)D and 25(OH)D2 levels are associated with handgrip strength status in middle-aged and elderly people in the 5 cities of Western China.

Objective:To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests.Methods:Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope ? hybridization and electron microscopy. Results:All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri′s bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope ? hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions:The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.