Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

AIM:To investigate the molecular mechanism of long noncoding RNA(lncRNA)SNHG1 in regu-lating ferroptosis to alleviate inflammation in CHME-5 human microglia induced by HIV-1 gp120 V3 loop.METHODS:CHME-5 human microglia were cultured in vitro,and were divided into 7 groups:blank group,random peptide group,gp120 V3 loop group(HIV-1 gp120 group),HIV-1 gp120+shCon group,HIV-1 gp120+SNHG1 sh2 group,HIV-1 gp120+SNHG1 sh2+ferrostatin-1(Fer-1;ferroptosis inhibitor)group,and HIV-1 gp120+SNHG1 sh2+EX527(Sirt1 in-hibitor)group.Normal CHME-5 cells were treated with random peptide or gp120 V3 loop for 24 h.After pretreatment of SNHG1 sh2 cells with inhibitors for 2 h,the cells were then treated with gp120 V3 loop for 24 h.The levels of inflammato-ry cytokines in the cell supernatants were detected by ELISA.Western blot was used to detect the protein expression levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),Sirt1 and p53.Microplate reader was used to detect the levels of intracellular ferrous ion(Fe2+)and malondialdehyde(MDA).RESULTS:(1)The results of ELISA showed that the expression levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1β in HIV-1 gp120 group were significantly higher than those in blank group(P<0.05).Compared with HIV-1 gp120 group,the ex-pression levels of inflammatory cytokines in HIV-1 gp120+SNHG1 sh2 group were significantly decreased(P<0.05).Compared with HIV-1 gp120+SNHG1 sh2 group,the expression levels of inflammatory factors in HIV-1 gp120+SNHG1 sh2+Fer-1 were significantly decreased(P<0.05),but those in HIV-1 gp120+SNHG1 sh2+EX527 group were significant-ly increased(P<0.01).(2)The results of Western blot showed that compared with blank group,the expression levels of ferroptosis-related proteins SLC7A11 and GPX4 in HIV-1 gp120 group were significantly down-regulated(P<0.01).Com-pared with HIV-1 gp120 group,the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2 group were sig-nificantly up-regulated(P<0.01).Compared with HIV-1 gp120+SNHG1 sh2 group,the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly up-regulated(P<0.05),but the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+EX527 group were significantly down-regulated(P<0.01),and the expression level of p53 was significantly up-regulated(P<0.05).(3)Compared with blank group,the levels of Fe2+and MDA in HIV-1 gp120 group were significantly increased(P<0.05).Compared with HIV-1 gp120 group,the levels of Fe2+and MDA in HIV-1 gp120+SNHG1 sh2 group were significantly decreased(P<0.01).Compared with HIV-1 gp120+SNHG1 sh2 group,Fe2+and MDA in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly decreased(P<0.05),but those in HIV-1 gp120+SNHG1 sh2+EX527 group was significantly increased(P<0.05).CONCLUSION:Knockdown of SNHG1 can attenuate the inflammation in microglia induced by HIV-1 gp120 V3 loop,which may be achieved by regulating ferrop-tosis-related signaling molecules through the Sirt1/p53 signaling pathway.

AIM:To explore the impact of histidine triad nucleotide-binding protein 2(HINT2)on atheroscle-rosis(AS),and to elucidate its underlying mechanisms.METHODS:Peripheral blood mononuclear cells(PBMCs)were isolated from patients with chest pain and induced to differentiate into macrophages for assessing HINT2 expression.In vitro,RAW264.7 mouse macrophages were cultured to evaluate inflammatory cytokine levels and cell death in superna-tants.An apolipoprotein E gene knockout(apoE-/-)mouse model of AS was developed to analyze plaque formation,lipid metabolism and macrophage foaminess in the aortic root.Pyroptosis-related protein expression in cultured RAW264.7 cells and the aorta of apoE-/-mice was determined by RT-qPCR and Western blot.RESULTS:Significantly reduced HINT2 expression was observed in PBMCs from patients with acute coronary syndrome,which was negatively correlated with pro-inflammatory and positively correlated with anti-inflammatory serum factors,suggesting HINT2's potential role in mitigating AS-related inflammation.In vitro experiments demonstrated that HINT2 overexpression inhibited lipid accumu-lation and foam cell formation in macrophages induced by oxidized low-density lipoprotein(ox-LDL).It also reduced se-cretion of inflammatory cytokines,including interleukin-6(IL-6),IL-1β,IL-18 and tumor necrosis factor-α,and de-creased cell death and pyroptosis-related protein expression.In vivo experiments in apoE-/-mice confirmed that HINT2 overexpression lessened plaque burden in the aortic root,reduced macrophage foaminess,and inhibited the expression of pyroptosis-related proteins such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,gasdermin D(GSDMD),IL-1β and IL-18.CONCLUSION:HINT2 potentially inhibits ox-LDL-induced macrophage pyroptosis,attenuates inflammatory responses in AS,and may slow the progression of this disease.

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10^-3 g·kg^-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg^-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β₁/drosophila mothers against decapentaplegic protein2/3（TGF-β₁/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β₁ proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.

Objective:To investigate the regional homogeneity (ReHo) among the major depressive disorder patients without mixed features (MDD noMF), major depressive disorder with mixed features (MMF), bipolar disorder with mixed features (BMF) and bipolar disorder patients without mixed features (BD noMF) patients, and to explore the brain activity and functional connectivity patterns of the MMF and BMF patients. Methods:This was a cross-sectional study. The MDD noMF patients (MDD noMF group), MMF patients (MMF group), BMF patients (BMF group), BD noMF patients (BD noMF group), and age-and gender-matched healthy controls (HC group) were recruited from Beijing Anding Hospital, Capital Medical University between April, 2021 and June, 2022. All the participants underwent resting-state functional MRI scanning. The ReHo values was computed with the DPABI software based on the MATLAB. Firstly, the difference in ReHo among the patients with MDD noMF, MMF, BMF, BD noMF and HC group were estimated by the analysis of covariance and the post-hoc method (LSD or Games-Howell). And then, the brain regions with significant different ReHo values were selected as the seeds to calculate the functional connectivity with the whole brain. Results:A total of 29 cases in the MDD noMF group, 24 cases in the MMF group, 26 cases in the BMF group, 29 cases in the BD noMF group, and 42 in the HC group were included. The differences in ReHo values in the left fusiform and the left precuneus of the 5 groups were statistically significant ( P<0.05). Among of them, the ReHo values of the left fusiform were lower in the MMF, BMF and BD noMF groups compared with the HC group ( P<0.05), while the ReHo values of the left precuneus in MDD noMF, MMF, BMF and BD noMF groups were higher than that in the HC group ( P<0.05). The ReHo value of the left fusiform was lower in the MMF group compared with the MDD noMF group ( P=0.001); the ReHo value of the left fusiform was lower in the BMF group compared with the MDD noMF and BD noMF groups ( P<0.05). The functional connectivity between the left fusiform and vermis, left insula, right putamen, and left medial superior frontal gyrus, and functional connectivity between the left precuneus and right superior frontal gyrus (dorsolateral) showed significant difference among the MDD noMF, MMF, BMF, BD noMF and HC groups ( P<0.05). Compared with HC group, MDD noMF, MMF, BD noMF groups showed higher functional connectivity between the left fusiform and the vermis, and MDD noMF, MMF, BMF, BD noMF group showed higher functional connectivityy between the the left fusiform and the left insula, left medial superior frontal gyrus and right putamen ( P<0.05). Compared with the MDD noMF group, the MMF, BMF and BD noMF groups showed higher functional connectivity between the left fusiform and the left insula ( P<0.05). Compared with the MDD noMF group, the BMF and BD noMF groups had higher functional connectivity between the left fusiform and the left medial superior frontal gyrus ( P<0.05). The BMF group showed higher functional connectivity of the left fusiform with the right putamen than the MDD noMF and BD noMF groups. Additonally, the BMF and BD noMF groups showed higher functional connectivity between the left precuneus and the right superior frontal gyrus (dorsolateral) than HC, MDD noMF and MMF groups ( P<0.05). Conclusions:MMF and BMF patients have local abnormalities of functional activity synchronization in the left fusiform and precuneus and abnormal functional connectivity patterns with multiple brain regions. MMF and BMF patients have specific neuroimaging features compared to MDD noMF or BD noMF patients and also share similar neuroimaging pathogenesis.

Background:There is no comparison of the current status of Helicobacter pylori(Hp)infection in different ethnic groups in terms of families and their individuals.Aims:To investigated for the first time the status of Hp infection in Tibetan and Han Chinese families at the household level.Methods:A questionnaire was used to investigate factors associated with Hp in 50 Tibetan families in Ya'an,Sichuan Province,and 50 Han Chinese families in Chongqing Municipality.13C-urea breath test was used to detect Hp infection.Results:The individual and household Hp positivity rates of the Tibetan population in southwest China were 47.10%and 80%,which were significantly higher than those of the Han Chinese,which were 27.81%and 58%(P<0.05).However,the difference between Han and Tibetan in individual and household infection rates was not statistically significant.There are differences between Han Chinese and Tibetans in terms of infection status,geography,economic conditions,living habits and levels of hygiene.Infection was concentrated in certain family groups rather than being evenly distributed in the population.Conclusions:The current detection rate of Hp infection in individuals and families of Tibetan residents is significantly higher than that of Han Chinese,while the proportion of infected individuals is not statistically different.Transmission of Hp is characterized by family aggregation.There are differences in infection status,geographical environment,economic conditions,living habits and hygiene levels between Chinese and Tibetan families.

Transcranial direct current stimulation (tDCS) is a well-tolerated, safe and noninvasive physical brain stimulation method, which has been widely used in the treatment of some common mental disorders and neurological diseases and has achieved certain clinical effects. It is necessary to develop expert consensus on clinical treatment to improve the use norms in related fields. According to the clinical research published before August 2021 and the method of evidence-based medicine, we published an expert consensus on tDCS in the treatment of depressive disorders, schizophrenia, substance use-related disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism, anxiety disorders, post-traumatic stress disorder, sleep disorders, pain, Parkinson′s disease, stroke, and epilepsy. The consensus also introduced the safety and efficacy of the clinical use of tDCS, and standardized the treatment process and operation technology, aiming to provide guidance for the clinical application of tDCS and promote the standardized development of this treatment technology in the future.