Hepatocellular carcinoma （HCC） is a common malignant tumor with a high mortality rate， an insidious onset， and complex pathological mechanisms. In the tumor microenvironment， tumor-promoting immune cells protect tumor cells from immune attacks， while dysfunction of anti-tumor immune cells causes the inhibition of immune response， thereby leading to the continuous deterioration of cancer. In recent years， traditional Chinese medicine has shown good efficacy in the treatment of HCC， and it can inhibit the proliferation and metastasis of cancer cells by regulating immune cells. By analyzing related articles in China and globally， this article summarizes how immune cells affect the progression of HCC through the immunosuppressive pathway and how traditional Chinese medicine exerts an anti-HCC effect by regulating immune cells， in order to provide theoretical basis and reference for optimizing the treatment of HCC.

BACKGROUND:Ischemic stroke is a highly prevalent disease associated with apoptosis.Neuronal death occurs after cerebral ischemia,including necrosis and apoptosis.The ischemic core region is dominated by necrosis,while delayed neuronal death in the penumbra is dominated by apoptosis.The penumbra has become a target for the treatment of ischemic stroke.This bibliometric analysis was used to identify the characteristics,hotspots,and frontiers of global scientific output related to apoptosis in ischemic stroke over the past 5 years. OBJECTIVE:To analyze the role of apoptosis and its mechanisms in the pathological process of ischemic stroke through a bibliometric approach. METHODS:A total of 927 relevant literature records from 2018 to 2022 were retrieved from Science Citation Index Expanded(SCI-Expanded)and Social Science Citation Index Expanded(SSCI-Expanded)of the Web of Science Core Collection.Research trends and hotspots of apoptosis in ischemic stroke were visualized using Citespace,VOSviewer and Bibliometrix. RESULTS AND CONCLUSION:From 2018 to 2020,the number of papers on the role of apoptosis in ischemic stroke showed an upward trend,but in 2020,the number of papers began to reduce.China had the largest number of publications,and the United States ranked the second.Capital Medical University and BRAIN RESEARCH BULLETIN were the institutions and journals with the most articles,respectively.In recent years,the two keywords"expression"and"oxidative stress"have appeared more frequently.The bibliometric study showed that in the past 5 years,most of the studies focused on basic research,in which research on the role of apoptosis in ischemic stroke has gradually decreased in the last 3 years,showing a downward trend.On the contrary,nerve regeneration has gradually become a research hotspot,especially the regulation of neurotrophic factors under the influence of different mechanisms,and the research on angiogenesis and glial cell repair is on the rise.At the same time,apoptosis in nerve regeneration is a potential point of discovery.

BACKGROUND:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells.The Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway plays an important role in the development of the disease.Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE:To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models,which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS:The literature related to the topic from January 2002 to December 2022 was searched in CNKI,WanFang and PubMed databases.A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION:The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response.The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells,destroying the integrity of the blood-brain barrier,and promoting the activation of T cells,B cells and microglia.By targeting TLRs,MyD88 and NF-κB molecules,inhibiting the activation or signal transduction of TLRs,MyD88 and NF-κB,and reducing the secretion of pro-inflammatory factors,multiple sclerosis can be treated.Animal studies have shown that active ingredients of traditional Chinese medicines,such as flavonoids and glycosides,and traditional Chinese medicine compound formulas,such as Buyang Huanwu Tang,can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway,which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis.

Objective To explore the method of objective identification of color information in sublingual veins diagnosis of TCM.Methods Combined with computer vision,compact fully convolution networks(CFCNs)and 19 deep learning classification models were used for study,and a double pulse rectangle algorithm was designed as a means of segmentation and recognition of sublingual veins and color information extraction.Results The accuracy of segmentation of tongue bottom obtained by the method of removing reflection + data expanding + data post-processing was 0.955 9,F1 value was 0.947 3,and mIoU value was 0.900 0.The accuracy of segmentation of sublingual veins obtained by the method of removing reflection + tongue input + data expanding + corrosion expansion was 0.778 4,F1 value was 0.738 3 and mIoU value was 0.585 1,which were obviously superior to the current classic or improved U-net model.On the color classification of sublingual veins,the best classification model was DenseNet161-bc-early_stopping with an accuracy rate of 0.803 7.Conclusion The deep learning method has a certain effect on identifying the color information of sublingual veins in TCM,which provides a new method for the research of quantitative color detection technology of sublingual veins diagnosis in TCM.

ObjectiveTo investigate whether cytotoxic T lymphocyte （CTL）－derived exosomes can downregulate HBx expression and inhibit hepatic stellate cell （HSC） activation. MethodsThe supernatants of HepG2， HepGA14， and CTL cells were collected to extract exosomes， which were referred to as NC－exo， HBV－exo， and CTL－exo， respectively）. Transmission electron microscopy was used to observe their morphology， and Western Blot was used to measure the expression of the markers of exosomes CD63 and TSG101. NC－exo， HBV－exo， and CTL－exo labeled by BODIPY dye were mixed with HBV－exo at different ratios and were then co－cultured with HSC LX－2 （HSC－LX2）. A fluorescence microscope was used to observe whether exosomes could enter LX－2 cells， and an fluorescence microscope was used to observe cell morphological changes； quantitative real－time PCR （qPCR） was used to measure the expression of the activated biomarkers such as transforming growth factor－β1 （TGF－β1）， ɑ－smooth muscle actin （ɑ－SMA）， and collagen type I （Collagen I） in LX－2 cells. CTL－exo was added to the HepGA14 culture system； then qPCR was used to measure the mRNA expression level of HBV DNA， cccDNA， and HBx in exosomes in HepGA14 cells， and Western Blot was used to measure the protein expression level of HBx in exosomes. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe exosomes were all microcysts with a double－layer membrane structure and were circular or elliptical in shape， with the expression of the signature proteins CD63 and TSG101， and the vesicles had a diameter of 50－100 nm. The fluorescence microscope showed that exosomes could enter LX－2 cells， and HSC were enlarged with extended cell processes. The results of qPCR showed that there were significant differences in the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes between the NC－exo， HBV－exo， NC－exo+HBV－exo， and Con groups （F=444.678， 417.144， and 571.508， all P<0.05）. After the intervention of HepGA14 cells with CTL－exo， qPCR results showed that compared with the control group， there were significant reductions in the expression levels of HBV DNA and cccDNA in HepGA14 cells （all P<0.05）， the relative mRNA expression level of HBx in exosomes （P<0.05）， and the protein expression level of HBx （P<0.05）. CTL－exo and HBV－exo were mixed at different ratios （2∶1， 5∶1， 10∶1） and were then used for the intervention of LX－2 cells， and qPCR results showed that the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes in LX－2 cells gradually decreased with the increase in the ratio of CTL－exo between groups （P<0.05）. ConclusionCTL－exo can downregulate the protein expression of HBx in HBV－exo to inhibit HSC activation， suggesting that CTL－exo has an anti－hepatitis B liver fibrosis effect.

Sleep disorder is a common problem that damages the quality of life in the elderly.At the same time, it is also related to the occurrence and development of insulin resistance, metabolic syndrome, Alzheimer's disease and other diseases.With the progress of aging in China, the sleep problems of the elderly have attracted more and more attention.Based on the sleep characteristics of elderly and the clinical manifestations of sleep disorders, this paper expounds the current situation using sleep disorders assessment scale, and puts forward the urgent need for independent development of sleep disorder assessment scale suitable for the elderly in China.

Objective To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. Methods SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. Results Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1β [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1β: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1β: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). Conclusion High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.

Objective:To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD + acute myeloid leukemia (AML) with normal karyotype. Methods:The clinical data of FLT3-ITD + AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results:The study included 49 patients with FLT3-ITD +AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD + ( P>0.05) . There were 12 patients with high-frequency FLT3-ITD + in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion:Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD + patients, particularly those with FLT3-ITD high-frequency mutation.

Objective:To analyze the relationship between nutritional status and frailty among elderly inpatients from cardiology department.Methods:A cross-sectional study was conducted in a total of 519 patients aged 65-92 years old who were admitted to cardiology department between September 2018 and February 2019. Mini nutritional assessment short form (MNA-SF) was used to assess the nutritional status. Fried phenotype was used to assess frailty status. The nutritional status and frailty in patients with different diseases, age and body mass index were analyzed, as well as the nutritional status of patients in different frailty strata.Results:The mean age was 75.12 years (range: 65-92 years). The prevalence of malnutrition risk was 28.9% (150/519), malnutrition 3.3% (17/519) and frailty 23.5% (122/519). When stratified by disease, the subgroup with chronic heart failure showed the highest prevalence of malnutrition and frailty (63.6% and 50.0%, respectively). The prevalence of malnutrition risk (22.8%, 35.5%), malnutrition (3.0%, 3.6%) and frailty (15.3%, 32.3%) were higher in patients ≥ 75 years compared with those aged 65 years - 75 years. MNA-SF score was negatively correlated with age( r = -0.134, P = 0.002). Fried phenotype score was positively correlated with age ( r = 0.319, P < 0.01). As for stratification based on BMI, the majority (62.6%) patients were overweight or obese (BMI ≥ 24.0 kg/m 2) and the prevalence of malnutrition risk in this subgroup was 21.2% (69/325). The prevalence of malnutrition risk in patients with normal BMI was 38.7% (70/181). The subgroup with BMI<18.5 were either at malnutrition risk or with malnutrition. MNA-SF score was positively correlated with BMI ( r = 0.353, P < 0.01). There was no significant difference in the prevalence of pre-frailty and frailty among different BMI groups. The prevalence of malnutrition was the highest in the frailty group (8.2%), followed by the pre-frailty group (2.0%). Fried phenotype score was negatively correlated with MNA-SF score( r = -0.291, P < 0.01). Logistic regression analysis showed that frailty was an independent risk factor for malnutrition, and the risk of malnutrition in frailty patients was 4.818 (95% CI:1.701～13.644) times higher than that in non-frailty patients. Conclusions:The prevalence of malnutrition risk and frailty was high in the elderly inpatients from cardiology department. Frailty patients had a higher incidence of malnutrition and required more attention.

Objective:To analyze the correlation among nutritional status, sarcopenia and frailty in elderly inpatients with chronic cardiovascular disease.Methods:A cross-sectional study was conducted in a total of 147 patients aged 65-88 years old who were hospitalized for chronic cardiovascular disease between September 2018 and February 2019. Nutritional status was assessed by mini nutritional assessment short form (MNA-SF), frailty by FRAIL scale and sarcopenia by criteria from Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. The prevalence and overlapping prevalence of nutritional status, frailty and sarcopenia were analyzed, as well as the influence of nutritional status on frailty and sarcopenia.Results:The mean age was 74.45 (range: 65-88). The prevalence was 25.9% (38/147) for risk of malnutrition, 1.4% (2/147) for malnutrition, 37.4% (55/147) for risk of sarcopenia, 6.8% (10/147) for sarcopenia, 55.8% (82/147) for pre-frailty and 10.2% (15/147) for frailty. When stratified by disease, the subgroup with chronic heart failure showed the highest prevalence of malnutrition risk, sarcopenia risk, sarcopenia and frailty (66.7%, 50%, 16.7% and 50.0%, respectively). The prevalence of sarcopenia risk and sarcopenia increased with age. Age was negatively correlated with calf circumference ( r = -0.219, P = 0.008), grip strength ( r = -0.307, P < 0.01) and walking speed ( r = -0.390, P < 0.01) and was positively correlated with the five times sit-to-stand test time ( r = 0.406, P < 0.01). The prevalence of frailty also increased with age and age was positively correlated with the FRAIL score ( r = 0.232, P = 0.005). As for stratification based on BMI, the majority (63.9%) patients were overweight or obese (BMI ≥ 24.0) and the prevalence of malnutrition risk in this subgroup was 20.2% (19/94). The prevalence of malnutrition risk in patients with normal BMI was 32.0% (16/50). The subgroup with BMI < 18.5 were either at malnutrition risk or with malnutrition. MNA-SF score was positively correlated with BMI ( r = 0.334, P < 0.01). The prevalence of sarcopenia risk and sarcopenia in patients with BMI ≥ 24.0 kg/m 2 was 23.4% (22/94) and 2.1% (2/94), that in normal BMI subgroup was 62.0% (31/50) and 14.0% (7/50), and that in BMI < 18.5 subgroup was 66.7% (2/3) and 33.3% (1/3). BMI was positively correlated with calf circumference ( r = 0.659, P < 0.01) and ASMI ( r = 0.367, P < 0.01). The overlapping prevalence of sarcopenia risk/sarcopenia and malnutrition risk/malnutrition was 13.6% (20/147), that of pre-frailty/frailty and malnutrition risk/malnutrition was 21.8% (32/147), and that of sarcopenia risk/sarcopenia and pre-frailty/frailty was 26.5% (39/147). The overlapping prevalence of sarcopenia risk/sarcopenia, malnutrition risk/malnutrition and pre-frailty/frailty was 10.9% (16/147). MNA-SF score was negatively correlated with FRAIL score ( r = -0.316, P < 0.01). The prevalence of pre-frailty/frailty in the malnutrition risk/malnutrition group was higher than that in the subgroup with normal nutritional status (80.0% vs. 60.7%, χ 2 = 4.808, P = 0.028). The prevalence of sarcopenia risk/sarcopenia in the malnutrition risk/malnutrition group tended to be higher than that in the subgroup with normal nutritional status (50.0% vs. 33.6%, χ 2 = 3.302, P = 0.069). Logistic regression analysis showed that the risk of pre-frailty/frailty was 2.585 (95% CI: 1.087 to 6.147) times higher in the malnutrition risk/malnutrition group. Conclusions:The prevalence and overlapping prevalence of malnutrition risk, pre-frailty and sarcopenia risk was high in the elderly inpatients hospitalized for chronic cardiovascular disease. Patients with malnutrition risk/malnutrition had a higher incidence of pre-frailty/frailty and required close attention.