Development of a Predictive Nomogram for Estimating Medication Nonadherence in Hemodialysis Patients.

BACKGROUND Medication compliance in hemodialysis patients affects the therapeutic effect of treatment and patient survival. Therefore, we aimed to explore the influencing factors of medication adherence in hemodialysis patients and develop a nomogram model to predict medication adherence. MATERIAL AND METHODS Data from questionnaires on medication adherence in hemodialysis patients were collected in Chengde from May 2020 to December 2020. The least absolute selection operator (LASSO) regression model and multivariable logistic regression analysis were used to analyze the risk factors for medication adherence in hemodialysis patients, and then a nomogram model was established. The bootstrap method was applied for internal validation. The concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), decision curve analysis (DCA), calibration curve, net reclassification improvement (NRI) index, and integrated discrimination improvement (IDI) index were used to evaluate the degree of differentiation and accuracy of the nomogram model, and clinical impact was used to investigate the potential clinical value of the nomogram model. RESULTS In total, 206 patients were included in this study, with a rate of medication nonadherence of 41.75%. Eight predictors were identified to build the nomogram model. The C-index, AUC, DCA, calibration curve, NRI, and IDI showed that the model had good discrimination and accuracy. The clinical impact plot showed that the nomogram of medication adherence in hemodialysis patients had clinical application value. CONCLUSIONS We developed and validated a nomogram model that is intuitive to apply for predicting medication adherence in hemodialysis patients.

A Novel CDK4/6 and PARP Dual Inhibitor ZC-22 Effectively Suppresses Tumor Growth and Improves the Response to Cisplatin Treatment in Breast and Ovarian Cancer.

In recent years, three PARP inhibitors and three CDK4/6 inhibitors have been approved by the FDA for the treatment of recurrent ovarian cancer and advanced ER-positive breast cancer, respectively. However, the clinical benefits of the PARPi or CDK4/6i monotherapy are not as satisfied as expected and benefit only a fraction of patients. Current studies have shown therapeutic synergy for combinations of PARPi and CDK4/6i in breast and ovarian cancers with homologous recombination (HR) proficiency, which represents a new synthetic lethal strategy for treatment of these cancers regardless HR status. Thus, any compounds or strategies that can combine PARP and CDK4/6 inhibition will likely have great potential in improving clinic outcomes and in benefiting more patients. In this study, we developed a novel compound, ZC-22, that effectively inhibited both PARP and CDK4/6. This dual-targeting compound significantly inhibited breast and ovarian cancer cells by inducing cell cycle arrest and severe DNA damage both in vitro and in vivo. Interestingly, the efficacy of ZC-22 is even higher than the combination of PARPi Olaparib and CDK4/6i Abemaciclib in most breast and ovarian cancer cells, suggesting that it may be an effective alternative for the PARPi and CDK4/6i combination therapy. Moreover, ZC-22 sensitized breast and ovarian cancer cells to cisplatin treatment, a widely used chemotherapeutic agent. Altogether, our study has demonstrated the potency of a novel CDK4/6 and PARP dual inhibitor, which can potentially be developed into a monotherapy or combinatorial therapy with cisplatin for breast and ovarian cancer patients with HR proficiency.

[Evaluation on Malaria Hotspots in Yingjiang County of the China-Myanmar Border Area in 2015].

Objective: To understand the control status of malaria at hotspots in Yingjiang County and provide measures for malaria elimination in the China-Myanmar border areas of Yunnan Province. Methods: A survey was made in 4 villages with indigenous malaria cases or imported cases in Nabang and Tongbiguan of Yingjiang County in Yunnan Province in June and July 2015. Peripheral blood samples were collected from the neighboring residents around patients and examined by malaria rapid diagnostic test （RDT）. The results were further verified by nested-PCR. Mosquitoes were collected by overnight trapping with light traps in Jingpo, Lilisu, Jiema, and Mengxiangyang villages or by human landing catches in Jingpo and Lisu villages. Nested-PCR was performed on part of the captured Anopheles minimus to detect the malaria parasites. Results: One hundred and ninety-four filter blood samples were collected from 11 malaria cases in two sites. All were detected to be negative for Plasmodium by RDT. In contrast, two samples originated from Jingpo and Lisu villages with indigenous cases were detected to be positive for Plasmodium vivax by nested-PCR. A total of 2 374 mosquitoes were captured, belonging to 22 species of 4 genera: Anopheles, Culex, Aedes and Armigeres. The mosquitoes were predominated by genus Culex, followed by genus Anopheles（11.33%, 269/2 374） which was dominated by A. minimus（49.07%, 132/269）, then was A. sinensis（4.09%, 11/269）, A. maculatus（2.23%, 6/269）, A. jeyporiensis（0.74%, 2/269）and so on. The mean indoor man-biting rate of mosquitoes was 5.78 and 3.20 per person per hour for Jingpo and Lisu villages, and the mean outdoor man-biting rate of mosquitoes was 2.30 per person per hour for Lisu Village. The 14 A. minimus were negative for sporozoite infection as detected by nested-PCR. Conclusion: Nested-PCR showed that there are asymptomatic Plasmodium carriers in Yingjiang's border area of Yunnan Province. Four major mosquito species as malaria vectors exist with A. minimus as the dominant one.

Amplification of pfmdr1, pfcrt, pvmdr1, and K13 propeller polymorphisms associated with Plasmodium falciparum and Plasmodium vivax isolates from the China-Myanmar border.

Malaria in the China-Myanmar border region is still severe; local transmission of both falciparum and vivax malaria persists, and there is a risk of geographically expanding antimalarial resistance. In this research, the pfmdr1, pfcrt, pvmdr1, and K13-propeller genotypes were determined in 26 Plasmodium falciparum and 64 Plasmodium vivax isolates from Yingjiang county of Yunnan province. The pfmdr1 (11.5%), pfcrt (34.6%), and pvmdr1 (3.1%) mutations were prevalent at the China-Myanmar border. The indigenous samples exhibited prevalences of 14.3%, 28.6%, and 14.3% for pfmdr1 N86Y, pfcrt K76T, and pfcrt M74I, respectively, whereas the samples from Myanmar showed prevalences of 10.5%, 21.1%, and 5.3%, respectively. The most prevalent genotypes of pfmdr1 and pfcrt were Y86Y184 and M74N75T76, respectively. No pvmdr1 mutation occurred in the indigenous samples but was observed in two cases coming from Myanmar. In addition, we are the first to report on 10 patients (38.5%) with five different K13 point mutations. The F446I allele is predominant (19.2%), and its prevalence was 28.6% in the indigenous samples of Yingjiang county and 15.8% in samples from Myanmar. The present data might be helpful for enrichment of the molecular surveillance of antimalarial resistance and useful for developing and updating guidance for the use of antimalarials in this region.

Coverage, use and maintenance of bed nets and related influence factors in Kachin Special Region II, northeastern Myanmar.

BACKGROUND: Myanmar is one of the 31 highest burden malaria countries worldwide. Scaling up the appropriate use of insecticide-treated nets (ITNs) is a national policy for malaria prevention and control. However, the data on use, influencing factors and maintenance of bed nets is still lack among the population in Kachin Special Region II (KR2), Northeastern Myanmar. METHODS: The study combined a quantitative household questionnaire survey and qualitative direct observation of households. A Chi-squared test was used to compare the percentages of ownership, coverage, and rates of use of bed nets. Additionally, multivariate logistic regression analysis (MVLRA) was used to analyse factors that influence the use of bed nets. Finally, covariance compared the mean calibrated hole indexes (MCHI) across potential influence variables. RESULTS: The bed net to person ratio was 1:1.96 (i.e., more than one net for every two people). The long-lasting insecticidal net (LLIN) to person ratio was 1: 2.52. Also, the percentage of households that owned at least one bed net was 99.7% (666/688). Some 3262 (97.3%) residents slept under bed nets the prior night, 2551 (76.1%) of which slept under ITNs/LLINs the prior night (SUITNPN). The poorest families, those with thatched roofing, those who use agriculture as their main source of family income, household heads who knew that mosquitoes transmit malaria and those who used bed nets to prevent malaria, were significantly more likely to be in the SUITNPN group. However, residents in lowlands, and foothills were significantly less likely to be SUITNPNs. Finally, head of household attitude towards fixing bed nets influenced MCHI (F=8.09, P=0.0046). CONCLUSIONS: The coverage and usage rates of bed nets were high, especially among children, and pregnant women. Family wealth index, geographical zones, household roofing, source of family income, household head's knowledge of malaria transmission and of using bed nets as tools for malaria prevention are all independent factors which influence use of ITNs/LLINs in KR2. Maintaining high coverage, and use rate of bed nets should be a priority for the war-torn population of KR2 to ensure equity and human rights.

In vivo monitoring of dihydroartemisinin-piperaquine sensitivity in Plasmodium falciparum along the China-Myanmar border of Yunnan Province, China from 2007 to 2013.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the recommended first-line treatment of falciparum malaria in all endemic countries. Artemisinin resistance in Plasmodium falciparum has been confirmed in the Greater Mekong subregion (GMS). Dihydroartemisinin-piperaquine (DAPQ) is the most commonly used ACT in China. To understand the DAPQ sensitivity of P. falciparum, DAPQ resistance was monitored in vivo along the China-Myanmar border from 2007 to 2013. METHODS: Eligible patients with mono-infections of P. falciparum were recruited to this study after obtaining full informed consent. DAPQ tablets for different categories of kg body weight ranges were given once a day for three days. Patients were followed up for 42 days. Polymerase chain reaction (PCR) was conducted to distinguish between re-infection and recrudescence, to confirm the Plasmodium species. The data were entered and analysed by the Kaplan-Meier method. Treatment outcome was assessed according to the WHO recommended standards. RESULTS: 243 patients were completed valid follow-up. The fever clearance time (FCT) and asexual parasite clearance times (APCT) were, respectively, 36.5 ± 10.9 and 43.5 ± 11.8 hours, and there was an increasing trend of both FCT (F = 268.41, P < 0.0001) and APCT (F = 88.6, P < 0.0001) from 2007 to 2013. Eight (3.3%, 95% confidence interval, 1.4-6.4%) patients present parasitaemia on day three after medication; however they were spontaneous cure on day four. 241 (99.2%; 95% CI, 97.1-99.9%) of the patients were adequate clinical and parasitological response (ACPR) and the proportions of ACPR had not changed significantly from 2007 to 2013 (X(2) = 2.81, P = 0.7288). CONCLUSION: In terms of efficacy, DAPQ is still an effective treatment for falciparum malaria. DAPQ sensitivity in P. falciparum had not significantly changed along the China-Myanmar border of Yunnan Province, China. However more attentions should be given to becoming slower fever and parasite clearance.

Monitoring Plasmodium vivax chloroquine sensitivity along China-Myanmar border of Yunnan Province, China during 2008-2013.

BACKGROUND: Plasmodium vivax is the most widespread of the malaria parasites infecting human hosts. In malaria-eliminating settings, both imported and local malaria predominantly occurs in border areas, and most of them are P. vivax. Chloroquine (CQ) is the first-line drug for P. vivax treatment in China. To understand CQ sensitivity in P. vivax, in vivo monitoring of CQ resistance was conducted along the China-Myanmar border from 2008 to 2013. METHODS: Eligible patients with mono-infections of P. vivax were recruited to this study after obtaining full informed consent. CQ tablets for different categories of kg body weight ranges were given once a day for three days. Patients were followed up for 28 days. PCR was conducted to distinguish between re-infection and recrudescence, to confirm the Plasmodium species. The data were entered and analysed by the Kaplan-Meier method. Treatment outcome and sensitivity were classified according to the WHO recommended standards. RESULTS: 603 patients were completed valid follow-up. The fever clearance time and asexual parasite clearance times were, respectively, 22.2 ± 10.2 and 38.1 ± 12.6 hours. 594 (98.5%) patients were adequate clinical and parasitological response (ACPR), and nine (1.5%) patients, who were late clinical failure (LCF) or resistant response level I (RI), were imported from the neighbouring districts of Myanmar. CONCLUSION: In terms of efficacy, CQ is still effective for vivax malaria treatment. Plasmodium vivax CQ sensitivity had not significantly changed along the China-Myanmar border of Yunnan Province, China.

The development of a clinical nomogram to predict medication nonadherence in patients with knee osteoarthritis.

Knee osteoarthritis (KOA) is a common bone disease in older patients. Medication adherence is of great significance in the prognosis of this disease. Therefore, this study analyzed the high-risk factors that lead to medication nonadherence in patients with KOA and constructed a nomogram risk prediction model. The basic information and clinical characteristics of inpatients diagnosed with KOA at the Department of Orthopedics, The Affiliated Hospital of Chengde Medical University, were collected from January 2020 to January 2022. The Chinese version of the eight-item Morisky scale was used to evaluate medication adherence. The Kellgren-Lawrence (KL) classification was performed in combination with the imaging data of patients. Least absolute shrinkage and selection operator regression analysis and logistic multivariate regression analysis were used to analyze high-risk factors leading to medication nonadherence, and a prediction model of the nomogram was constructed. The model was internally verified using bootstrap self-sampling. The index of concordance (C-index), area under the operating characteristic curve (AUC), decision curve, correction curve, and clinical impact curve were used to evaluate the model. A total of 236 patients with KOA were included in this study, and the non-adherence rate to medication was 55.08%. Seven influencing factors were included in the nomogram prediction: age, underlying diseases, diabetes, age-adjusted Charlson comorbidity index (aCCI), payment method, painkillers, and use of traditional Chinese medicine. The C-index and AUC was 0.935. The threshold probability of the decision curve analysis was 0.02-0.98. The nomogram model can be effectively applied to predict the risk of medication adherence in patients with KOA, which is helpful for medical workers to identify and predict the risk of individualized medication adherence in patients with KOA at an early stage of treatment, and then carry out early intervention.

Single-port robotic surgery for mediastinal tumors using the da vinci SP system: Initial experience.

Purpose: Studies of single-port robot-assisted thoracic surgery (RATS) using the da Vinci SP system, which uses a smaller surgical incision than the conventional multiport robot, have yet to be reported because of its smaller operating range. We report our initial experience using the da Vinci SP system in thoracic surgery for the resection of mediastinal tumors that requires a smaller workspace. Description: Two patients diagnosed with superior mediastinal tumors underwent RATS performed with the da Vinci SP surgical system in January 2022. We used three-dimensional reconstruction to preoperatively determine the surgical incision. This is the first report of single-port RATS using the SP system in China. Evaluation: R0 resection was achieved in both operations without complications. Operation times and bleeding volumes were similar to the use of multiport RATS. No perioperative complications occurred. Conclusions: The da Vinci SP system can be used for the resection of superior mediastinal tumors. Case selection and preoperative planning should be performed prior to these surgeries.

Nutritional Changes and Early Warning of Moldy Rice under Different Relative Humidity and Storage Temperature.

Processed unhusked rice is prone to mildew during storage. In this study, the storage conditions were simulated at temperatures of 20, 30, and 35 °C and a relative humidity of 40%, 60% and 80%, respectively. The water, fatty acid, and total starch content and the peak viscosity, mold colony number, protein secondary structure, and spatial structure of rice were monitored in order to propose the critical point of mildew during storage. In the process of rice from lively to moldy, the water content, fatty acid contents and the peak viscosity were increased. The total starch content decreased and then showed a slow increasing trend, while the microstructure of the powder particles changed from smooth and complete to loosen and hollow. With the increase in storage time, the vibration of the amide Ⅰ band of the rice samples decreased slightly, indicating that the total contents of ß-fold, ß-turn, α-helix, and random curl of the rice protein also changed. PCA (Principal Component Analysis) analysis showed that rice mildew index was closely related to temperature and humidity during storage. In our investigation, the best and most suitable temperature and relative humidity for rice storge is 20 °C and 40%, respectively. These results suggested that temperature and environmental humidity are vital factors affecting the physicochemical properties and nutrient changes, which provides a theoretical basis for the early warning of rice mildew during storage.

Initial experience with robotic-assisted thoracic surgery for superior mediastinal masses.

Objective: Minimally invasive surgery is challenging for masses located in the superior mediastinum, especially for those close to the chest outlet. This study aimed to evaluate the feasibility and safety of robotic-assisted thoracic surgery (RATS) for these masses. Methods: From June 2015 to January 2020, 35 patients (19 males, 16 females), with a mean age of 41.6 (range, 13-66) years, underwent RATS for the treatment of superior mediastinal masses. Data regarding the operation time, blood loss, pathology, conversion rate, morbidity, mortality, and cost were collected and analyzed. Results: The mean (±standard deviation) operation time, blood loss, chest tube use duration, and postoperative hospital day were 117 ± 45.2 (range, 60-270) min, 59.7 ± 94.4 (range, 10-500) ml, 4.1 ± 2.1 (range, 1-10) days, and 5.1 ± 2.1 (range, 2-11) days, respectively. The pathological diagnoses included schwannoma (26 cases), ganglioneuroma (4 cases), bronchogenic cysts (3 cases), ectopic nodular goiter (1 case), and cavernous hemangioma (1 case). The mean diameter of the resected tumor was 4.6 ± 2.0 (range, 2.5-10) cm. No conversion or mortality occurred. Postoperative complications included Horner's syndrome (18 cases: 6 patients with preoperative Horner's syndrome), weakened muscular power (2 cases), and chylothorax (2 cases). The mean cost was $ 8,868.7 (range, $ 4,951-15,883). Conclusions: Our experience demonstrated that RATS is safe and feasible for superior mediastinal mass resection. However, the high incidence of postoperative Horner's syndrome requires further research.

Urantide decreases hepatic steatosis in rats with experimental atherosclerosis via the MAPK/Erk/JNK pathway.

Hepatic steatosis, an indicator of atherosclerosis (AS), is always accompanied by inflammatory responses and disturbances in lipid metabolism. The present study investigated the protective effect of urantide, a urotensin II (UII) receptor antagonist, on the liver of rats with AS with hepatic steatosis by regulating the MAPK pathway. AS was induced in rats via an intraperitoneal injection of vitamin D3 and the administration of a high­fat diet. Urantide treatment was then administered to the rats. Pathology, liver index, lipid levels and liver function were measured to determine liver injury. The expression levels of UII and G protein­coupled receptor 14 (GPR14) were determined using immunohistochemistry, reverse transcription­quantitative PCR and western blotting. The expression levels of MAPK­related proteins in hepatocytes from each group were quantified using western blotting and immunofluorescence staining. Rats with AS had typical pathological changes associated with AS and hepatic steatosis, which were significantly improved by urantide treatment. Blood lipid levels, body weight, liver index and liver function were recovered in rats with AS after urantide treatment. Urantide downregulated the expression levels of UII and GPR14 in the livers of rats with AS; concurrently, the phosphorylation of Erk1/2 and JNK was significantly decreased. Moreover, no significant changes were observed in the phosphorylation of p38 MAPK in AS rat livers. In conclusion, urantide inhibits the activation of Erk1/2 and JNK by blocking the binding of UII and GPR14, thereby alleviating hepatic steatosis in rats with AS, ultimately restoring lipid metabolism in the liver and alleviating AS lesions.

PD-L1 and Immune Infiltration of m6A RNA Methylation Regulators and Its miRNA Regulators in Hepatocellular Carcinoma.

BACKGROUND: The aim of this study was to systematically evaluate the relationship between the expression of m6A RNA methylation regulators and prognosis in HCC. METHODS: We compared the expression of m6A methylation modulators and PD-L1 between HCC and normal in TCGA database. HCC samples were divided into two subtypes by consensus clustering of data from m6A RNA methylation regulators. The differences in PD-L1, immune infiltration, and prognosis between the two subtypes were further compared. The LASSO regression was used to build a risk score for m6A modulators. In addition, we identified miRNAs that regulate m6A regulators. RESULTS: We found that fourteen m6A regulatory genes were significantly differentially expressed between HCC and normal. HCC samples were divided into two clusters. Of these, there are higher PD-L1 expression and poorer overall survival (OS) in cluster 1. There was a significant difference in immune cell infiltration between cluster 1 and cluster 2. Through the LASSO model, we obtained 12 m6A methylation regulators to construct a prognostic risk score. Compared with patients with a high-risk score, patients with a low-risk score had upregulated PD-L1 expression and worse prognosis. There was a significant correlation between risk score and tumor-infiltrating immune cells. Finally, we found that miR-142 may be the important regulator for m6A RNA methylation in HCC. CONCLUSION: Our results suggest that m6A RNA methylation modulators may affect the prognosis through PD-L1 and immune cell infiltration in HCC patients. In addition, the two clusters may be beneficial for prognostic stratification and improving immunotherapeutic efficacy.

CD317 Promotes the survival of cancer cells through apoptosis-inducing factor.

BACKGROUND: Low nutrient environment is a major obstacle to solid tumor growth. However, many tumors have developed adaptive mechanisms to circumvent the requirement for exogenous growth factors. METHODS: Here we used siRNA interference or plasmid transfection techniques to knockdown or enhance CD317 expression respectively, in mammalian cancer cells, and subjected these CD317-manipulated cells to serum deprivation to study the role of CD317 on stress-induced apoptosis and the underlying mechanism. RESULTS: We report that CD317, an innate immune gene overexpressed in human cancers, protected cancer cells against serum deprivation-induced apoptosis. In tumor cells, loss of CD317 markedly enhanced their susceptibility to serum deprivation-induced apoptosis with no effect on autophagy or caspase activation, indicating an autophagy- and caspase-independent mechanism of CD317 function. Importantly, CD317 knockdown in serum-deprived tumor cells impaired mitochondria function and subsequently promoted apoptosis-inducing factor (AIF) release and nuclear translocation but had little effect on mitochondrial and cytoplasmic distributions of cytochrome C, a pro-apoptotic factor released from mitochondria that initiates caspase processing in response to death stimuli. Furthermore, overexpression of CD317 in HEK293T cells inhibits serum deprivation-induced apoptosis as well as the release and nuclear accumulation of AIF. CONCLUSION: Our data suggest that CD317 functions as an anti-apoptotic factor through the mitochondria-AIF axis in malnourished condition and may serve as a potential drug target for cancer therapy.

Competition between Plasmodium falciparum strains in clinical infections during in vitro culture adaptation.

We evaluated the dynamics of parasite populations during in vitro culture adaptation in 15 mixed Plasmodium falciparum infections, which were collected from a hypoendemic area near the China-Myanmar border. Allele types at the msp1 block 2 in the initial clinical samples and during subsequent culture were quantified weekly using a quantitative PCR method. All mixed infections carried two allele types based on the msp1 genotyping result. We also genotyped several polymorphic sites in the dhfr, dhps and mdr1 genes on day 0 and day 28, which showed that most of the common sites analyzed were monomorphic. Two of the three clinical samples mixed at dhps 581 remained stable while one changed to wild-type during the culture. During in vitro culture, we observed a gradual loss of parasite populations with 10 of the 15 mixed infections becoming monoclonal by day 28 based on the msp1 allele type. In most cases, the more abundant msp1 allele types in the clinical blood samples at the beginning of culture became the sole or predominant allele types on day 28. These results suggest that some parasites may have growth advantages and the loss of parasite populations during culture adaptation of mixed infections may lead to biased results when comparing the phenotypes such as drug sensitivity of the culture-adapted parasites.

Baicalin regulates neuronal fate decision in neural stem/progenitor cells and stimulates hippocampal neurogenesis in adult rats.

BACKGROUND: Recent studies revealed that baicalin, a flavonoid compound derived from the root of Scutellaria baicalensis Georgi, could promote neuron differentiation of NSPCs after commencing the differentiation process in vitro. However, this may not be the most efficacious strategy to determinate cell fate. Here, we have investigated whether baicalin can influence early events of neuron generation and stimulate adult neurogenesis. RESULTS: Transient exposure of NSPCs to baicalin during proliferation could activate Mash1 to alter the differential fate and increase the proportion of cells expressing neuronal markers. Seven days after, rats were exposed to transient cerebral ischemia, they were treated for 3 weeks with baicalin, BrdU labeling study showed that exposure to baicalin increased the number of newly generated cells in hippocampus, BrdU/NeuN double staining analysis indicated that baicalin could promote new neuron production after cerebral ischemia. Additionally, Morris water maze test showed that delayed postischemic treatment with baicalin improved cognitive impairment. CONCLUSIONS: These results identify the existence of a single molecule, baicalin, which can specify the neuronal fate of multipotent NSPCs and stimulate neurogenesis, making it a promising candidate for developing clinically relevant strategies to manipulate neuronal fate of NSPCs for brain repair.

Direct stimulation of adult neural stem/progenitor cells in vitro and neurogenesis in vivo by salvianolic acid B.

BACKGROUND: Small molecules have been shown to modulate the neurogenesis processes. In search for new therapeutic drugs, the herbs used in traditional medicines for neurogenesis are promising candidates. METHODOLOGY AND PRINCIPAL FINDINGS: We selected a total of 45 natural compounds from Traditional Chinese herbal medicines which are extensively used in China to treat stroke clinically, and tested their proliferation-inducing activities on neural stem/progenitor cells (NSPCs). The screening results showed that salvianolic acid B (Sal B) displayed marked effects on the induction of proliferation of NSPCs. We further demonstrated that Sal B promoted NSPCs proliferation in dose- and time-dependent manners. To explore the molecular mechanism, PI3K/Akt, MEK/ERK and Notch signaling pathways were investigated. Cell proliferation assay demonstrated that Ly294002 (PI3K/Akt inhibitor), but neither U0126 (ERK inhibitor) nor DAPT (Notch inhibitor) inhibited the Sal B-induced proliferation of cells. Western Blotting results showed that stimulation of NSPCs with Sal B enhanced the phosphorylation of Akt, and Ly294002 abolished this effect, confirming the role of Akt in Sal B mediated proliferation of NSPCs. Rats exposed to transient cerebral ischemia were treated for 4 weeks with Sal B from the 7th day after stroke. BrdU incorporation assay results showed that exposure Sal B could maintain the proliferation of NSPCs after cerebral ischemia. Morris water maze test showed that delayed post-ischemic treatment with Sal B improved cognitive impairment after stroke in rats. SIGNIFICANCE: Sal B could maintain the NSPCs self-renew and promote proliferation, which was mediated by PI3K/Akt signal pathway. And delayed post-ischemic treatment with Sal B improved cognitive impairment after stroke in rats. These findings suggested that Sal B may act as a potential drug in treatment of brain injury or neurodegenerative diseases.