BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.

Objective To establish the characteristic atlas of Shexiang Jiegu Capsule and determine the contents of seven active components （hydroxysafflor Yellow A, paeoniflorin, ferulic acid, naringin, ligustilide, catechin, epicatechin）. Methods Octadecyl silane bonded silica gel was used as the filling agent, the mobile phase was composed of methanol-0.05% phosphoric acid by gradient elution, the detection wavelength was 245 nm, flow rate was 1.0 ml/min, column temperature was 30℃. The similarity of the fifteen batches of sample was evaluated in line with the TCM Chromatographic Fingerprint （2012 edition）, and the contents of seven active components were determined. Results The HPLC fingerprint of Shexiang Jiegu Capsules was established. The similarity of fingerprint between fifteen batches of samples and control fingerprint was between 0.893 and 0.992. The results of methodological investigation for the determination of seven active components in fifteen batches of samples all met the requirements. Conclusion The established characteristic atlas of Shexiang Jiegu Capsules had high specificity and good repeatability, which could provide scientific basis for quality control of Shexiang Jiegu Capsules.

Objective To explore the molecular mechanism of luteolin in the treatment of cervical cancer based on network pharmacology and molecular docking technology. Methods The drug-like properties of luteolin were analyzed by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The targets of luteolin were obtained from PharmMapper, Super-PRED, and Swiss Target Prediction databases. The targets related to cervical cancer were acquired from GeneCards, OMIM, and PharmGKB databases. The intersection targets of luteolin and cervical cancer were obtained through EVenn, and the "luteolin-intersection targets-cervical cancer" network diagram was constructed by Cytoscape 3.8.1. The STRING database was used to analyze the protein-protein interaction (PPI) network of intersection targets and screen the core targets. The Database for Annotation, Visualization and Integrated Discovery (David) was used to conduct Gene Ontology (GO) gene function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis of the targets. PyMoL 2.6.0, AutoDockTool 1.5.7 and OpenBabel 2.4.1 software were used to perform molecular docking between the core targets and luteolin. The survival analysis and pan-cancer analysis of the core targets were performed in the GEPIA database. Results A total of 449 targets of luteolin and 1 334 targets related to cervical cancer were obtained; there were 100 intersection targets between luteolin and cervical cancer, of which 24 were core targets, including MMP2, HRAS, MAPK1, AKT1, RHOA and PGR. GO and KEGG enrichment analyses revealed that the intersection targets participated in 455 biological processes, 70 cellular components, 119 molecular functions, and 143 KEGG signaling pathways. Molecular docking revealed a good binding of MMP2 with luteolin. The survival curves of cervical cancer patients showed that the risk ratios of RHOA, MAPK1, MMP2 and AKT1 genes were greater than 1, while those of HRAS and PGR were less than 1. Pan-cancer analysis showed that HRAS and MAPK1 were highly expressed in cervical cancer, and HRAS had significant expression differences. Conclusion Luteolin treats cervical cancer through a multi-target and multi-pathway mechanism.

Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Prospective Studies ; HIV Infections/drug therapy* ; Anti-HIV Agents/therapeutic use* ; Comorbidity

Objective: To systematically assess the effectiveness and safety of using acupuncture-moxibustion therapy alone to treat adult overactive bladder (OAB) by taking oral Western medication solely as the control, and to provide evidence-based reference for acupuncture-moxibustion treatment of OAB. Methods: A systemic search was conducted through China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), PubMed, Cochrane Library, and Excerpta Medica Database (EMBASE). RevMan 5.3 was used for meta-analysis. Statistical descriptions were made using standardized mean difference (SMD), confidence interval (CI), and risk ratio (RR). Results: Eight randomized controlled studies were finally recruited and were analyzed after being grouped according to intervention methods. Regarding urinary symptoms, compared with sole use of oral Western medication, acupuncture plus moxibustion can more effectively reduce 24 h urinary frequency [P=0.01, SMD=-0.57, 95％CI (-1.02, -0.12)], 24 h nocturia frequency [P=0.03, SMD=0.49, 95％CI (0.05, 0.94)], and OAB syndrome score (OABSS) [P<0.001, SMD=-3.67, 95％CI (-4.48, -2.86)]. Acupuncture combined with moxibustion and oral Western medication work equivalently in comparing 24 h urinary urgency frequency [P=0.38, SMD=-0.17, 95％CI (-0.57, 0.22)], 24 h urgent incontinence frequency [P=0.25, SMD=0.26, 95％CI (-0.18, 0.70)], and single voiding volume [P=0.22, SMD=1.15, 95％CI (-0.70, 3.00)]. There were no significant differences between acupuncture/electroacupuncture and oral medication in comparing 24 h urinary frequency [P=0.46, SMD=0.07, 95％CI (-0.12, 0.26)], 24 h urinary urgency frequency [P=0.18, SMD=0.70, 95％CI (-1.71, 0.32)], 24 h nocturia frequency [P=0.46, SMD=-0.71, 95％CI (-2.60, 1.17)], 24 h urgent incontinence frequency [P=0.08, SMD=-0.22, 95％CI (-0.48, 0.03)], single voiding volume [P=0.09, SMD=0.17, 95％CI (-0.02, 0.36)], or OABSS [P=0.96, SMD=-0.07, 95％CI (-2.65, 2.52)]. Compared with oral Western medication, moxibustion can more effectively reduce 24 h urinary frequency [P<0.001, SMD=-6.53, 95％CI (-7.65, -5.44)] and 24 h urinary urgency frequency [P<0.001, SMD=-1.6, 95％CI (-2.85, -0.36)]. In comparing the adverse reaction rate, acupuncture-moxibustion was associated with a lower rate compared with oral medication [P=0.002, RR=0.07, 95％CI (0.01, 0.37)], but the difference was statistically insignificant between acupuncture/electroacupuncture and oral medication [P=0.40, RR=0.57, 95％CI (0.16, 2.12)]. Conclusion: Acupuncture-moxibustion is equivalent to the sole use of oral Western medication in improving urinary symptoms in OAB patients and has a higher safety rating.

The proteolysis targeting chimeras (PROTACs) technology has been rapidly developed since its birth in 2001, attracting rapidly growing attention of scientific institutes and pharmaceutical companies. At present, a variety of small molecule PROTACs have entered the clinical trial. However, as small molecule PROTACs flourish, non-small molecule PROTACs (NSM-PROTACs) such as peptide PROTACs, nucleic acid PROTACs and antibody PROTACs have also advanced considerably over recent years, exhibiting the unique characters beyond the small molecule PROTACs. Here, we briefly introduce the types of NSM-PROTACs, describe the advantages of NSM-PROTACs, and summarize the development of NSM-PROTACs so far in detail. We hope this article could not only provide useful insights into NSM-PROTACs, but also expand the research interest of NSM-PROTACs.

Objective:To explore the correlation between socioeconomic status (SES) and diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D).Methods:A total of 276 T2D patients admitted to the Second Affiliated Hospital of Nanjing Medical University from January to June 2020 were enrolled in this cross-sectional study. The estimated glomerular filtration rate (eGFR) was calculated according to the urinary albumin/creatinine ratio (UACR) and the chronic kidney disease epidemiology collaboration equation(CKD-EPI formula) based on serum creatinine. The patients were divided into simple T2D group (184 cases) and DKD group (92 cases). Collect demographic and laboratory examination data, record education, income and occupation, and calculate standardized SES scores. According to SES scores, subjects were divided in three levels: SES≤9, SES≥10-≤12, and SES≥13. Student's t test was used for comparison of measurement data with normal distribution between two groups, and one-way ANOVA was used for comparison between multiple groups. Non-normal distribution was represented by M( Q1, Q3), and rank-sum test was used for comparison between groups. Counting data were expressed as frequency or percentage, and chi-square test was used for comparison between groups. Bofferoni test was further used for pairwise comparison of indicators with statistical significance among multiple groups. Spearman correlation analysis was used to analyze the correlation between variables. The risk factors were analyzed by binary Logistic regression. Results:The age of the subjects was (53.37±10.68) years, men accounted for 55.8% (154/276), the duration of diabetes was 60.00 (12.00, 134.00) months, and eGFR was (97.56±21.15) mL/(min·1.73 m 2). In simple T2D group and DKD group, prevalence of hypertension were 39.7% (73/184) and 57.6% (53/92), systolic blood pressure were (129.43±14.92) mmHg and (139.29±17.61) mmHg, diastolic blood pressure were (81.86±10.06) mmHg and (87.74±11.19) mmHg, serum albumin were (45.74±4.15) g/L and (43.99±5.05) g/L, triglycerides were (1.82±1.24) mmol/L and (2.64±2.92) mmol/L, high density lipoprotein cholesterol were (1.17±0.37) mmol/L and (1.07±0.26) mmol/L, serum uric acid were (298.44±90.73) μmol/L and (336.22±94.01) μmol/L, serum creatinine were (62.83±14.45) μmol/L and (87.75±57.37) μmol/L, eGFR were (102.6±14.28) mL/(min·1.73 m 2) and (87.47±28.04) mL/(min·1.73 m 2), UACR were (7.60 (4.63, 13.15)) mg/g and (93.95 (47.25, 310.25)) mg/g. Prevalence of hypertension, systolic blood pressure, diastolic blood pressure, triglycerides, serum uric acid, serum creatinine, UACR in DKD group were higher than those in simple T2D group. Serum albumin, high density lipoprotein cholesterol and eGFR in DKD group were lower than those in simple T2D group. There was significant difference between the two groups ( χ2=7.95, t values were 4.87, 4.40, 3.04, 3.26, 2.30, 3.22, 5.56, 5.95, Z=13.07, P values were 0.005, <0.001, <0.001, 0.003, 0.001, 0.022, 0.001, <0.001, <0.001, and <0.001, respectively). The number of males in the three groups with SES ≥13 group, SES≥10-≤12 group, SES ≤9 group were 61 (81.3%, 61/75), 55 (59.8%, 55/92), 38 (34.9%, 38/109), respectively. The number of cases with smoking history were 42 (56.0%, 42/75), 41 (44.6%, 41/92), 35 (32.1%, 35/109), respectively. The number of cases with drinking history were 38 (50.7%, 38/75), 32 (34.8%, 32/92), 26 (23.9%, 26/109), respectively. The ages were (47.77±10.76), (52.76±11.22), (57.74±7.96) years old, respectively. Body mass index (BMI) were (26.17±3.87), (24.96±3.93), (24.27±4.89) kg/m 2, respectively. High density lipoprotein cholesterol (HDL) were (1.03±1.03), (1.16±0.41), (1.21±0.32) mmol/L, respectively. Serum uric acid were (336.56±82.05), (293.78±94.78), (307.99±96.53) μmol/L, respectively. EGFR were (105.03±19.72), (99.77±19.44), (90.57±21.49) mL/(min·1.73 m 2),respectively.The difference between groups were statistically significant (χ 2=39.79, 10.55, 14.08, F=22.69, 4.03, 6.20, 4.53, 12.02, P values were <0.001, 0.005, 0.001, <0.001, 0.019, 0.002, 0.012, and <0.001, respectively). Pairwise comparison shows that male and eGFR in SES ≤9 group were lower than those in SES ≥13 group and SES≥10-≤12 group, age in SES ≤9 group was higher than that in SES ≥13 group and SES≥10-≤12 group. The difference was statistically significant (all P<0.05). Smoking history, alcohol history and BMI in SES ≤9 group were lower than those in SES ≥13 group, and the high density lipoprotein cholesterol in SES ≤9 were higher than that in SES ≥13 group. The difference was statistically significant (all P<0.05). Male, alcohol history and serum uric acid in SES≥10-≤12 group were lower than those in SES ≥13 group, and age and high density lipoprotein cholesterol in SES≥10-≤12 group were higher than those in SES ≥13 group. The difference was statistically significant (all P<0.05). Spearman correlation analysis showed that SES in T2D was positively correlated with male, smoking history, alcohol history, BMI, serum uric acid and eGFR ( r values were 0.38, 0.20, 0.24, 0.16, 0.13 and 0.31, P values were <0.001, 0.001, <0.001, 0.008, 0.028, and <0.001, respectively), and negatively correlated with age, high density lipoprotein cholesterol and UACR ( r values were -0.35, -0.24 and -0.14, P values were <0.001, <0.001, and 0.017, respectively). Logistic regression analysis showed that SES (OR=2.71,95% CI:1.10-6.68, P=0.031) was associated with T2DM combined with DKD. The risk of developing DKD increased when the SES was ≤9. Conclusion:The SES in patients with type 2 diabetes is closely related to DKD. Low SES may be a new risk factor for DKD in type 2 diabetic patients.

Objective: To evaluate the feasibility of autoregressive integrated moving average with explanatory variables ( ARIMAX ) model including meteorological factors on the prediction of influenza-like illness ( ILI ), so as to provide a basis for the monitoring and early warning of influenza. Methods: The ILI data reported by four sentinel hospitals in Yuhang District of Hangzhou from the 1st week of 2014 to the 26th week of 2018 was collected, as well as the meteorological data during the same period. The ARIMAX model was established using the percentage of ILI cases in total outpatients ( ILI% ) data from the 1st week of 2014 to the 52nd week of 2017 and the meteorological factors selected by Lasso regression model. The ILI% from the 1st to 26th week of 2018 was predicted and compared with the actual values to verify the ARIMAX model. Results: From the 1st week of 2014 to the 26th week of 2018, a total of 60 419 cases of ILI were reported by the four sentinel hospitals of Yuhang District, with ILI% of 1.29%. Lasso regression analysis showed that there was a positive correlation between weekly average absolute humidity and ILI% ( r=27.769 ), and a negative correlation between weekly average temperature and ILI% ( r=-0.117 ). The ARIMAX (1, 0, 0) ( 1, 0, 0 )12 with weekly average temperature and absolute humidity was selected as the optimal model, with the Bayesian information criterion (BIC) value of 81.30 and the mean absolute percentage error (MAPE) value of 15.77%. The MAPE value of the ARIMAX model predicting the ILI% from 1st to 26th week of 2018 were 43.75%. Conclusion The ARIMAX model including meteorological factors can be used to predict the prevalence of ILI, but the accuracy needs to be promoted.

There is an imbalance between the supply and demand of functional red blood cells (RBCs) in clinical appli-cations. This imbalance can be addressed by regenerating RBCs using several in vitro methods. Induced pluripotent stem cells (iPSCs) can handle the low supply of cord blood and the ethical issues in embryonic stem cell research, and provide a promising strategy to eliminate immune rejection. However, no complete single-cell level differentiation pathway exists for the iPSC-derived erythroid differentiation system. In this study, we used iPSC line BC1 to establish a RBC regeneration system. The 10X Genomics single-cell transcriptome platform was used to map the cell lineage and differentiation trajectory on day 14 of the regeneration system. We observed that iPSC differentiation was not synchronized during embryoid body (EB) culture. The cells (on day 14) mainly consisted of mesodermal and various blood cells, similar to the yolk sac hematopoiesis. We identified six cell classifications and characterized the regulatory transcription factor (TF) networks and cell–cell contacts underlying the system. iPSCs undergo two transformations during the differentiation trajectory, accompanied by the dynamic expression of cell adhesion molecules and estrogen-responsive genes. We iden-tified erythroid cells at different stages, such as burst-forming unit erythroid (BFU-E) and orthochromatic erythroblast (ortho-E) cells, and found that the regulation of TFs (e.g., TFDP1 and FOXO3) is erythroid-stage specific. Immune erythroid cells were identified in our system. This study provides systematic theoretical guidance for optimizing the iPSC-derived erythroid differentiation system, and this system is a useful model for simulating in vivo hematopoietic develo-pment and differentiation.

The Genome Sequence Archive (GSA) is a data repository for archiving raw sequence data, which provides data storage and sharing services for worldwide scientific communities. Considering explosive data growth with diverse data types, here we present the GSA family by expanding into a set of resources for raw data archive with different purposes, namely, GSA (https://ngdc.cncb.ac.cn/gsa/), GSA for Human (GSA-Human, https://ngdc.cncb.ac.cn/gsa-human/), and Open Archive for Miscellaneous Data (OMIX, https://ngdc.cncb.ac.cn/omix/). Compared with the 2017 version, GSA has been significantly updated in data model, online functionalities, and web interfaces. GSA-Human, as a new partner of GSA, is a data repository specialized in human genetics-related data with controlled access and security. OMIX, as a critical complement to the two resources mentioned above, is an open archive for miscellaneous data. Together, all these resources form a family of resources dedicated to archiving explosive data with diverse types, accepting data submissions from all over the world, and providing free open access to all publicly available data in support of worldwide research activities.