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.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Since the outbreak of COVID-19, several prevention and control measures have been successively promulgated in Wuhan. To name a few, setup of designated hospitals for severe COVID-19 patients is key to enforcing the policy of pooling patients, experts, resources and standardizing treatment. These efforts contribute decisively to improving the cure rate and reducing the mortality of COVID-19. As one of the designated hospitals composed of multiple medical teams, Wuhan Union Hospital put in place a joint working mode for treating severe COVID-19 patients, and found solutions to the main problems and difficulties in management. Its experiences provide references for the operation of joint medical institutions in emergency.

OBJECTIVETo study the relationship between daily temperature and non-accidental deaths in four districts of Jinan, and to investigate the impact of temperature on cause-specific mortality.

METHODSData on daily mortality of the four districts (Shizhong, Huaiyin, Tianqiao, Lixia) as well as data related to meteorology and air pollution index were collected from January 1, 2008 to December 31, 2012. Distributed lag non-linear model (DLNM) was then used to assess the effects of temperature on all non-accidental deaths and deaths caused by cardiovascular diseases (CVD), respiratory diseases (RD), digestive diseases, urinary diseases, and also subcategories to hypertension, ischemic heart diseases (IHD), acute myocardial infarction (AMI), cerebro-vascular diseases (CBD) and chronic lower respiratory diseases.

RESULTSA W-shaped relationship was noticed between daily average temperature and non-accidental deaths. The effect of low temperature last for more than 30 days, much longer than that of high temperature, in which presented a harvesting effect less than 5 days. As to the cause-specific mortality, short-term heat effects were seen in CVD and RD as well as related subgroups as IHD, CBD and AMI, with RRs at lag 0 as 1.12 (95%CI:1.07-1.17), 1.06 (95% CI:1.02-1.31), 1.08 (95% CI:1.003-1.16), 1.10 (95% CI:1.02-1.20) and 1.13 (95% CI: 1.003-1.26). Relatively higher RRs were seen in urinary diseases and hypertension under extremely high temperature, reaching as high as 2.30 (95%CI:1.18-4.51) and 1.65 (95%CI:1.02-2.69). Cold weather presented a delayed effect for 30 days, with cumulative RRs as 1.51 (95%CI:1.42-1.60), 1.90 (95%CI:1.64-2.20), 2.12 (95%CI:1.67-2.69), 1.48 (95%CI:1.08-2.03), 1.60 (95%CI:1.46-1.75), 1.40 (95%CI:1.26-1.55), 1.68 (95%CI:1.45-1.95) for CVD, RD, chronic lower respiratory diseases, hypertension,IHD, CBD and AMI, on sequence.

CONCLUSIONA relationship was seen between daily temperature and non-accidental deaths as well as cause-specific mortality. Either high or low temperature seemed to be detrimental. Related measures on disease prevention should be taken during the cold and hot seasons.

Cause of Death ; China ; epidemiology ; Humans ; Mortality ; Nonlinear Dynamics ; Temperature

OBJECTIVETo find out the differences in regional characteristics of heat vulnerability between people living in urban centers and urban-fringe areas of Jinan city so as to provide basis for the development of adaptation measures to heat.

METHODSA cross-sectional survey on heat vulnerability was conducted in urban center and urban-fringe areas of Jinan city, using a self-designed questionnaire among 801 residents at the age of 16 years or older in August 2013. Data of 23 indicators related to heat vulnerability were collected and aggregated to 7 dimensions:health and medical insurance, social networks, heat perception and adaptive behavior, economic status, resources, living environment and working environment. An index score was calculated using a balanced weighted average approach for each dimension, ranging from 0 to 1, with the closer to 1 as greater vulnerability.

RESULTSThe scores on heat perception and adaptive behavior, economic status, resources and working environment dimensions for urban-fringe areas were 0.42,0.63,0.55 and 0.62, statistically significantly higher than the urban center area of 0.41,0.51,0.26 and 0.41. Scores of living environment, social networks and health/medical insurance dimensions for urban center area were 0.57,0.49 and 0.31, which were all higher than the urban-fringe areas of 0.50,0.46 and 0.25, with differences statistically significant.

CONCLUSIONResidents living in the urban center might be more vulnerable to heat in terms of living environment, health/medical insurance and social networks while residents living in the urban-fringe areas might more be vulnerable in terms of heat perception and adaptive behavior, economic status, life resources and working environment. These facts indicated that heat vulnerability among residents could be quite different, even at a fine geographic sale. We would thus suggest that intervention strategies on protecting people from heat, should be more targeted.

Adolescent ; Adult ; Aged ; China ; Cross-Sectional Studies ; Female ; Health Status ; Hot Temperature ; Humans ; Male ; Middle Aged ; Surveys and Questionnaires ; Urban Population ; statistics & numerical data ; Young Adult

Objective To find out the differences in regional characteristics of heat vulnerability between people living in urban centers and urban-fringe areas of Jinan city so as to provide basis for the development of adaptation measures to heat. Methods A cross-sectional survey on heat vulnerability was conducted in urban center and urban-fringe areas of Jinan city,using a self-designed questionnaire among 801 residents at the age of 16 years or older in August 2013. Data of 23 indicators related to heat vulnerability were collected and aggregated to 7 dimensions:health and medical insurance,social networks,heat perception and adaptive behavior,economic status,resources, living environment and working environment. An index score was calculated using a balanced weighted average approach for each dimension,ranging from 0 to 1,with the closer to 1 as greater vulnerability. Results The scores on heat perception and adaptive behavior,economic status, resources and working environment dimensions for urban-fringe areas were 0.42,0.63,0.55 and 0.62, statistically significantly higher than the urban center area of 0.41,0.51,0.26 and 0.41. Scores of living environment,social networks and health/medical insurance dimensions for urban center area were 0.57,0.49 and 0.31,which were all higher than the urban-fringe areas of 0.50,0.46 and 0.25, with differences statistically significant. Conclusion Residents living in the urban center might be more vulnerable to heat in terms of living environment,health/medical insurance and social networks while residents living in the urban-fringe areas might more be vulnerable in terms of heat perception and adaptive behavior,economic status,life resources and working environment. These facts indicated that heat vulnerability among residents could be quite different,even at a fine geographic sale. We would thus suggest that intervention strategies on protecting people from heat,should be more targeted.

Objective To study the relationship between daily temperature and non-accidental deaths in four districts of Jinan,and to investigate the impact of temperature on cause-specific mortality. Methods Data on daily mortality of the four districts(Shizhong,Huaiyin,Tianqiao,Lixia) as well as data related to meteorology and air pollution index were collected from January 1,2008 to December 31,2012. Distributed lag non-linear model(DLNM)was then used to assess the effects of temperature on all non-accidental deaths and deaths caused by cardiovascular diseases (CVD), respiratory diseases(RD),digestive diseases,urinary diseases,and also subcategories to hypertension, ischemic heart diseases(IHD),acute myocardial infarction(AMI),cerebro-vascular diseases(CBD) and chronic lower respiratory diseases. Results A W-shaped relationship was noticed between daily average temperature and non-accidental deaths. The effect of low temperature last for more than 30 days,much longer than that of high temperature,in which presented a harvesting effect less than 5 days. As to the cause-specific mortality,short-term heat effects were seen in CVD and RD as well as related subgroups as IHD,CBD and AMI,with RRs at lag 0 as 1.12(95%CI:1.07-1.17),1.06 (95%CI:1.02-1.31),1.08(95%CI:1.003-1.16),1.10(95%CI:1.02-1.20) and 1.13 (95%CI:1.003-1.26). Relatively higher RRs were seen in urinary diseases and hypertension under extremely high temperature,reaching as high as 2.30(95%CI:1.18-4.51)and 1.65(95%CI:1.02-2.69). Cold weather presented a delayed effect for 30 days,with cumulative RRs as 1.51(95%CI:1.42-1.60),1.90 (95%CI:1.64-2.20),2.12(95%CI:1.67-2.69),1.48(95%CI:1.08-2.03),1.60(95%CI:1.46-1.75), 1.40(95%CI:1.26-1.55),1.68(95%CI:1.45-1.95)for CVD,RD,chronic lower respiratory diseases, hypertension,IHD,CBD and AMI,on sequence. Conclusion A relationship was seen between daily temperature and non-accidental deaths as well as cause-specific mortality. Either high or low temperature seemed to be detrimental. Related measures on disease prevention should be taken during the cold and hot seasons.

Objective To search for the neutralizing epitopos on hepatitis E virus (HEV) capsid besides the known neutralizing epitope (aa459-606). Methods By analysis of several strains of monoclonal antibodies against HEV capsid and their recognized epitopes, the neutralizing activity of epitope (aa394-458) at N-terminus was compared with that of an immunodominant neutralizing epitope (an459-606). Re-suits The research showed a novel potential neutralizing epitope in aa423-437 of HEV ORF2 though detec-ting and comparing the characteristics of several antibodies and corresponding determinations. The epitope is a linear non-immunodominant epitope which is different from the other neutralizing epitope in aa459-606.And the amino acids sequence of this novel epitope is conservative. Conclusion ORF2 aa423-437 is a no-vel potential neutralizing leaner epitope of HEV. It is believed that the present work adds fundamental knowl-edge to our understanding of HEV capsid domain and contributes to the prevention and control of this dis-ease.

Objective Cloning and expression of Par6A.Methods Par6A cDNA was amplified from rat L6 skeletal muscle cells by RT-PCR and the cloning and expression vectors of Par6A were constructed.The expression vector was transfected into 293 cells.Furthermore,the function of Par6A was confirmed by Co-immunoprecipitation.Results Par6A cDNA with approximately 1 kb in length was successfully amplified,and the expression vector of pDsRed-Express-N1-Par6A was constructed.The red fluorescene was seen under fluorescent microscope after 293ET cells were transfected for 24 h using the pDsRed-Express-N1-Par6A vector.The expressed Par6A protein can interacte with PKC?.Conclusion We successfully cloned the Par6A cDNA from rat L6 skeletal muscle cells,which provided a reliable method to study the function of Par6A.