ObjectiveTo systematically evaluate the efficacy and safety of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines in the treatment of coronary microvascular disease （CMD）. MethodsPubMed， Cochrane Library， CNKI， Wanfang Data， and VIP were searched for the randomized controlled trials （RCTs） on the treatment of CMD with Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis with the time interval from inception to December 31， 2023. The primary outcome indicators included the index of microcirculatory resistance （IMR）， coronary flow reserve （CFR）， and corrected TIMI flow frame count （cTFC）. The secondary outcome indicators included symptomatic efficacy， left ventricular ejection fraction （LVEF）， hypersensitive C-reactive protein （hs-CRP）， nitric oxide （NO）， and adverse events. Cochrane risk-of-bias assessment tool 2.0 （RoB 2.0） and Stata 17.0 were used for literature quality evaluation and meta-analysis of the included RCTs. The Grading of Recommendations， Assessment， Development and Evaluation （GRADE） was used to evaluate the quality of evidence. ResultsA total of 36 RCTs were included in this study， involving 3 029 patients. Compared with conventional Western medicine alone， the combined use of Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis and Western medicine reduced the IMR ［mean difference （MD）=-5.93， 95% confidence interval （95%CI） ［-8.73，-3.14］， n=382， P<0.01］， cTFC （MD=-9.35， 95%CI ［-13.94，-4.76］， n=618， P<0.01）， and hs-CRP ［standard mean difference （SMD）=-1.50， 95%CI ［-1.90，-1.11］， n=1 483， P<0.01］， improved the CFR （SMD=1.14， 95%CI ［0.08，2.19］， n=304， P=0.03）， symptomatic efficacy ［relative risk （RR）=1.36， 95%CI ［1.21，1.53］， n=756， P<0.01］， LVEF （MD=4.39， 95%CI ［2.31，6.47］， n=533， P<0.01）， and NO （SMD=3.16， 95%CI ［2.07，4.25］， n=946， P<0.01） of CMD patients. In terms of safety， the combined therapy reduced the occurrence of adverse events in CMD patients （RR=0.49， 95%CI ［0.29，0.82］， n=591， P=0.01）. GRADE showed moderate quality evidence for adverse events， low quality evidence for cTFC， symptomatic efficacy， LVEF， and NO， and very low quality evidence for IMR， CFR， and hs-CRP. ConclusionBased on microcirculatory function indicators， the combined use of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines and Western medicine may further improve the coronary microvascular function in CMD patients with good safety. The above conclusions remain to be verified with high-quality clinical trials.

Objective To establish the therapeutic effect prediction model of platelet transfusion in hematological patients,and receiver operating characteristic(ROC)curve and clinical cases are used to evaluate the clinical application value of the predic-tion model.Methods A total of 485 patients with hematological diseases who received platelet transfusion therapy in Kailuan General Hospital from January 2020 to December 2023 were selected,corrected count increment(CCI)was used to divide the patients into platelet transfusion effective group(n=340)and transfusion ineffective group(n=145).Multivariate Logistic regres-sion analysis was used to establish the prediction model of platelet infusion efficacy,and ROC curve was used to evaluate the application effect of the forcasting model.109 clinical cases were used to verify the practical application effect of the model,and the sensitivity,specificity and accuracy were calculated.Results Among 485 patients with hematological diseases,the incidence of ineffective platelet transfusion was 29.90%(145/485).Compated with the effective group,the ineffective group had more previous platelet transfusions was higher,and the difference was statistically significant(t=-4.435,P<0.05).In the ineffective group,there were more cases of hyperplenism,aplastic anemia and lymphoma,higher infection rate and higher positive rate of platelet antibody,and the differences were statistically significant(χ2=6.301～37.522,all P<0.05).Multivariate Logistic regres-sion analysis found that previous platelet infusion times,infection,leukemia,aplastic anemia and platelet antibodies were risk factors for ineffective platelet transfusion in patients with hematological diseases(Wald χ2=5.224～21.548,all P<0.05).Based on these risk factors,platelet infusion effect prediction models 1 and 2 were constructed.ROC curve was used to evaluate the application effect of the prediction model.The area under the curve(AUC),cut-offpoint,sensitivity and specificity of model 1 were 0.884,0.042,82.35%,88.89%.The AUC,cut-offpoint,corresponding sensitivity and specificity of prediction model 2 were 0.910,59.784,81.18%,94.44%,respectively.The Z values of model 1 and model 2 were 12.159 and 13.151,respectively.The prediction effect of model 2 was better than that of model 1.The actual application results showed that the sensitivity,specificity and accuracy of prediction model 1,2 were 85.71%,92.05%,90.89%and 90.48%,93.18%,92.66%,respectively.Conclusion The ineffective rate of platelet transfusion in hematological patients is relatively high.The prediction models 1 and 2 for platelet transfusion effectiveness have good results in predicting ineffective platelet transfusion,and prediction model 2 is better than pre-diction model 1,which can provide reliable basis for hematological patients on accurate platelet transfusion.

Objective:To explore the feasibility of joint screening of the two primary immunodeficiency diseases [severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia(XLA)] and spinal muscular atrophy(SMA) in newborns by multiplex real-time quantitative PCR technology, and to provide evidence for early screening, diagnosis and treatment of children.Methods:Cross-sectional study. From July 2021 to January 2023, a total of 103 240 dry blood spots samples of newborns were collected which were delivered to Neonatal Disease Screening Center of Zhejiang by cold chain transportation. The concentrations of the T cell receptor excision ring (TREC), Kappa deletion of the recombinant excision loop (KREC), and exon 7 deletion of Survival Motor Neuron 1 (SMN1) gene in dry blood spots were simultaneously detected by multiplex real-time fluorescence quantitative PCR, taken ribonuclease P/MRP 30 000 subunits (RPP30) as an internal reference gene. The positive newborns were further diagnosed by other laboratory tests and gene sequencing was taken as gold standard. Children samples from 1 case of SCID, 3 cases of XLA and 2 cases of SMA were used for positive verification. The correlation between detected concentration of TREC/KREC and basic information in newborns were analyzed. The differences among groups for each factor were analyzed.Results:One case of SCID, 2 cases of XLA, 9 cases of SMA and 7 cases of other genetic diseases (4 cases of DiGeorge syndrome, 1 case of trisomy 21 syndrome, 1 case of Noonan syndrome and 1 case of super male syndrome) were identified by multiplex real-time fluorescence quantitative PCR. The positive predictive values of screening neonatal SCID, XLA and SMA were 2.44% (1/41), 2.78% (2/72) and 9/9 respectively. Taking the samples from clinically diagnosed 1 case of SCID, 3 cases of XLA and 2 cases of SMA as positive validation samples, which were all identified. The detected results of TREC/KREC correlated with time of blood collection, sex, weight, gestational age and delivery mode of newborns, whose r values were 0.162/0.187, 0.066/0.032, 0.045/0.042, ?0.015/?0.088 and 0.014/0.068 respectively (all P<0.05). Conclusions:Relying on current neonatal screening platform in Zhejiang, it is feasible to screen jointly two kinds of primary immunodeficiency diseases and spinal muscular atrophy in newborns by multiple real-time fluorescence quantitative PCR technology.

The incidence of falls is high among the elderly population,particularly in patients with dementia.It was associated with their quality of life,accelerated disease progression,and reducing life expectancy.However,there is still a lack of relevant guidelines and recommendations for the occurrence,prediction,and intervention of falls in people with dementia.By reviewing the epidemiology,pathogenesis,risk factors,prediction models,and intervention measures related to falls in patients with dementia to provide a reference for clinicians to manage the whole process management of senile dementia patients.It was shown a higher risk of falling in elderly with dementia,which may be associated with visuospatial impairment,executive dysfunction,motor dysfunction,poor nutritional status,and a decline in daily living ability.Falling directly affects the prognosis of patients and increases the social and medical burden,which needs to be paid attention to.

Background and Aims:Valeric acid activates the nuclear factor E2-related factor 2(Nrf2)pathway.Recent studies have demonstrated its potent antitumor activity in breast and oral cancers.However,its role in gastric cancer treatment remains unclear.This study aimed to investigate the effects of valeric acid on inflammatory responses and survival in a gastric cancer xenograft model in nude mice and to explore the potential underlying mechanisms to provide new insights for gastric cancer therapy.Methods:A xenograft model was established by subcutaneous injection of human gastric cancer MKN-45 cells into 80 Balb/c nude mice,which were then equally randomized into four groups:control and low-,medium-,and high-dose valeric acid groups(10,20,and 40 mg/kg,respectively).The mice received daily intraperitoneal injections of either saline or valeric acid for 30 days.Tumor growth was monitored during the treatment period.Twelve hours after the final administration,five mice from each group were sacrificed by cervical dislocation;blood was collected via eyeball removal,and tumors were excised and weighed.Histopathological changes in the tumors were observed by HE staining.Serum levels of macrophage inflammatory protein-2(MIP-2),interleukin-10(IL-10),and tumor necrosis factor α(TNF-α)were measured by ELISA.mRNA and protein expression levels of Nrf2 and its downstream molecules,quinone oxidoreductase-1(NQO-1)and heme oxygenase-1(HO-1),were assessed in tumor tissues using qRT-PCR and Western blot.The remaining 15 mice per group were monitored for survival analysis.Results:Compared with the control group,all valeric acid-treated groups showed a significant reduction in tumor volumes at all observation time points and final tumor weight(all P＜0.05),with a dose-dependent trend.HE staining revealed densely arranged tumor cells with high cell density in the control group,while various degrees of tumor necrosis and reduced cell density were observed in valeric acid-treated groups,most pronounced in the high-dose group.ELISA results showed that serum levels of MIP-2 and TNF-α were significantly decreased,while IL-10 levels were significantly increased in valeric acid-treated groups compared to controls(all P＜0.05),exhibiting dose dependence.qRT-PCR and Western blot analyses demonstrated that the mRNA and protein expression levels of Nrf2,HO-1,and NQO-1 in tumors were significantly elevated in the valeric acid groups compared with the control group(all P＜0.05),also showing dose dependence.Survival analysis indicated that the median survival times were 47 d(control),68 d(low dose),81 d(medium dose),and 90 d(high dose),with all valeric acid groups having significantly prolonged survival compared to the control group(all P＜0.05).Conclusion:Valeric acid effectively inhibits the growth of gastric cancer xenografts,attenuates systemic inflammatory responses,and prolongs the survival of nude mice,possibly through activation of the Nrf2 pathway and modulation of the tumor microenvironment.

Background and Aims:Valeric acid activates the nuclear factor E2-related factor 2(Nrf2)pathway.Recent studies have demonstrated its potent antitumor activity in breast and oral cancers.However,its role in gastric cancer treatment remains unclear.This study aimed to investigate the effects of valeric acid on inflammatory responses and survival in a gastric cancer xenograft model in nude mice and to explore the potential underlying mechanisms to provide new insights for gastric cancer therapy.Methods:A xenograft model was established by subcutaneous injection of human gastric cancer MKN-45 cells into 80 Balb/c nude mice,which were then equally randomized into four groups:control and low-,medium-,and high-dose valeric acid groups(10,20,and 40 mg/kg,respectively).The mice received daily intraperitoneal injections of either saline or valeric acid for 30 days.Tumor growth was monitored during the treatment period.Twelve hours after the final administration,five mice from each group were sacrificed by cervical dislocation;blood was collected via eyeball removal,and tumors were excised and weighed.Histopathological changes in the tumors were observed by HE staining.Serum levels of macrophage inflammatory protein-2(MIP-2),interleukin-10(IL-10),and tumor necrosis factor α(TNF-α)were measured by ELISA.mRNA and protein expression levels of Nrf2 and its downstream molecules,quinone oxidoreductase-1(NQO-1)and heme oxygenase-1(HO-1),were assessed in tumor tissues using qRT-PCR and Western blot.The remaining 15 mice per group were monitored for survival analysis.Results:Compared with the control group,all valeric acid-treated groups showed a significant reduction in tumor volumes at all observation time points and final tumor weight(all P＜0.05),with a dose-dependent trend.HE staining revealed densely arranged tumor cells with high cell density in the control group,while various degrees of tumor necrosis and reduced cell density were observed in valeric acid-treated groups,most pronounced in the high-dose group.ELISA results showed that serum levels of MIP-2 and TNF-α were significantly decreased,while IL-10 levels were significantly increased in valeric acid-treated groups compared to controls(all P＜0.05),exhibiting dose dependence.qRT-PCR and Western blot analyses demonstrated that the mRNA and protein expression levels of Nrf2,HO-1,and NQO-1 in tumors were significantly elevated in the valeric acid groups compared with the control group(all P＜0.05),also showing dose dependence.Survival analysis indicated that the median survival times were 47 d(control),68 d(low dose),81 d(medium dose),and 90 d(high dose),with all valeric acid groups having significantly prolonged survival compared to the control group(all P＜0.05).Conclusion:Valeric acid effectively inhibits the growth of gastric cancer xenografts,attenuates systemic inflammatory responses,and prolongs the survival of nude mice,possibly through activation of the Nrf2 pathway and modulation of the tumor microenvironment.

The incidence of falls is high among the elderly population,particularly in patients with dementia.It was associated with their quality of life,accelerated disease progression,and reducing life expectancy.However,there is still a lack of relevant guidelines and recommendations for the occurrence,prediction,and intervention of falls in people with dementia.By reviewing the epidemiology,pathogenesis,risk factors,prediction models,and intervention measures related to falls in patients with dementia to provide a reference for clinicians to manage the whole process management of senile dementia patients.It was shown a higher risk of falling in elderly with dementia,which may be associated with visuospatial impairment,executive dysfunction,motor dysfunction,poor nutritional status,and a decline in daily living ability.Falling directly affects the prognosis of patients and increases the social and medical burden,which needs to be paid attention to.

Objective To establish the therapeutic effect prediction model of platelet transfusion in hematological patients,and receiver operating characteristic(ROC)curve and clinical cases are used to evaluate the clinical application value of the predic-tion model.Methods A total of 485 patients with hematological diseases who received platelet transfusion therapy in Kailuan General Hospital from January 2020 to December 2023 were selected,corrected count increment(CCI)was used to divide the patients into platelet transfusion effective group(n=340)and transfusion ineffective group(n=145).Multivariate Logistic regres-sion analysis was used to establish the prediction model of platelet infusion efficacy,and ROC curve was used to evaluate the application effect of the forcasting model.109 clinical cases were used to verify the practical application effect of the model,and the sensitivity,specificity and accuracy were calculated.Results Among 485 patients with hematological diseases,the incidence of ineffective platelet transfusion was 29.90%(145/485).Compated with the effective group,the ineffective group had more previous platelet transfusions was higher,and the difference was statistically significant(t=-4.435,P<0.05).In the ineffective group,there were more cases of hyperplenism,aplastic anemia and lymphoma,higher infection rate and higher positive rate of platelet antibody,and the differences were statistically significant(χ2=6.301～37.522,all P<0.05).Multivariate Logistic regres-sion analysis found that previous platelet infusion times,infection,leukemia,aplastic anemia and platelet antibodies were risk factors for ineffective platelet transfusion in patients with hematological diseases(Wald χ2=5.224～21.548,all P<0.05).Based on these risk factors,platelet infusion effect prediction models 1 and 2 were constructed.ROC curve was used to evaluate the application effect of the prediction model.The area under the curve(AUC),cut-offpoint,sensitivity and specificity of model 1 were 0.884,0.042,82.35%,88.89%.The AUC,cut-offpoint,corresponding sensitivity and specificity of prediction model 2 were 0.910,59.784,81.18%,94.44%,respectively.The Z values of model 1 and model 2 were 12.159 and 13.151,respectively.The prediction effect of model 2 was better than that of model 1.The actual application results showed that the sensitivity,specificity and accuracy of prediction model 1,2 were 85.71%,92.05%,90.89%and 90.48%,93.18%,92.66%,respectively.Conclusion The ineffective rate of platelet transfusion in hematological patients is relatively high.The prediction models 1 and 2 for platelet transfusion effectiveness have good results in predicting ineffective platelet transfusion,and prediction model 2 is better than pre-diction model 1,which can provide reliable basis for hematological patients on accurate platelet transfusion.

Objective:To explore the feasibility of joint screening of the two primary immunodeficiency diseases [severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia(XLA)] and spinal muscular atrophy(SMA) in newborns by multiplex real-time quantitative PCR technology, and to provide evidence for early screening, diagnosis and treatment of children.Methods:Cross-sectional study. From July 2021 to January 2023, a total of 103 240 dry blood spots samples of newborns were collected which were delivered to Neonatal Disease Screening Center of Zhejiang by cold chain transportation. The concentrations of the T cell receptor excision ring (TREC), Kappa deletion of the recombinant excision loop (KREC), and exon 7 deletion of Survival Motor Neuron 1 (SMN1) gene in dry blood spots were simultaneously detected by multiplex real-time fluorescence quantitative PCR, taken ribonuclease P/MRP 30 000 subunits (RPP30) as an internal reference gene. The positive newborns were further diagnosed by other laboratory tests and gene sequencing was taken as gold standard. Children samples from 1 case of SCID, 3 cases of XLA and 2 cases of SMA were used for positive verification. The correlation between detected concentration of TREC/KREC and basic information in newborns were analyzed. The differences among groups for each factor were analyzed.Results:One case of SCID, 2 cases of XLA, 9 cases of SMA and 7 cases of other genetic diseases (4 cases of DiGeorge syndrome, 1 case of trisomy 21 syndrome, 1 case of Noonan syndrome and 1 case of super male syndrome) were identified by multiplex real-time fluorescence quantitative PCR. The positive predictive values of screening neonatal SCID, XLA and SMA were 2.44% (1/41), 2.78% (2/72) and 9/9 respectively. Taking the samples from clinically diagnosed 1 case of SCID, 3 cases of XLA and 2 cases of SMA as positive validation samples, which were all identified. The detected results of TREC/KREC correlated with time of blood collection, sex, weight, gestational age and delivery mode of newborns, whose r values were 0.162/0.187, 0.066/0.032, 0.045/0.042, ?0.015/?0.088 and 0.014/0.068 respectively (all P<0.05). Conclusions:Relying on current neonatal screening platform in Zhejiang, it is feasible to screen jointly two kinds of primary immunodeficiency diseases and spinal muscular atrophy in newborns by multiple real-time fluorescence quantitative PCR technology.

Medium spiny neurons (MSNs) in the striatum, which can be divided into D1 and D2 MSNs, originate from the lateral ganglionic eminence (LGE). Previously, we reported that Six3 is a downstream target of Sp8/Sp9 in the transcriptional regulatory cascade of D2 MSN development and that conditionally knocking out Six3 leads to a severe loss of D2 MSNs. Here, we showed that Six3 mainly functions in D2 MSN precursor cells and gradually loses its function as D2 MSNs mature. Conditional deletion of Six3 had little effect on cell proliferation but blocked the differentiation of D2 MSN precursor cells. In addition, conditional overexpression of Six3 promoted the differentiation of precursor cells in the LGE. We measured an increase of apoptosis in the postnatal striatum of conditional Six3-knockout mice. This suggests that, in the absence of Six3, abnormally differentiated D2 MSNs are eliminated by programmed cell death. These results further identify Six3 as an important regulatory element during D2 MSN differentiation.