Clinical analysis of the efficacies of ganciclovir plus foscarnet and a single antiviral drug for the treatment of cytomegalovirus infection after haploidentical stem cell transplantation / 中华内科杂志

Objective:To evaluate and compare the efficacies of ganciclovir plus foscarnet and a single agent for the treatment of cytomegalovirus (CMV) infection after haploidentical hematopoietic stem cell transplantation.Methods:This study was a non-randomized clinical controlled trial. The data of patients who underwent haploidentical transplantation and developed CMV infection between January 1, 2021, and June 30, 2021, were retrospectively analyzed. Follow-up was conducted through telephone, inpatient consultations, and the review of outpatient medical records. The observed indicators included the incidence of CMV infection (including CMV disease), rate of recurrence of CMV infection, overall survival (OS), and disease-free survival (DFS).Results:A total of 242 patients were diagnosed with post-transplantation CMV infection; 116 patients tested positive for CMV DNA for more than 14 days ( P=0.011). Of the 242 patients with CMV infection, 65 were treated with ganciclovir plus foscarnet, and 156 patients were treated with a single antiviral drug; the median durations of CMV seroconversion were 21 (3-60) and 14 (3-32) days for the combination and single-drug groups, respectively. There were no significant differences between their incidence of CMV infections and 1-year OS and DFS. Of the patients with refractory CMV infections, 53 (45.7%) were treated with ganciclovir plus foscarnet, and 63 (54.3%) were treated with a single antiviral agent. The median durations of CMV seroconversion for the combination and single-drug groups were 21 (15-60) days and 20 (15-45) days, respectively ( P=0.472). Two patients in each group progressed to CMV disease ( P=0.860). During follow-up, 12 patients (22.6%) in the combination group and 8 patients (12.7%) in the single-drug group experienced recurrent episode(s) of CMV infection ( P=0.158). The 1-year OS of the combination and single-drug groups were 92.0% and 87.1%, respectively ( P=0.543); the 1-year DFS were 90.3% and 85.7%, respectively ( P=0.665). Univariate analysis revealed no associations between the antiviral agents used and OS and DFS (OS: HR=0.644, P=0.547; DFS: HR=0.757, P=0.666). Conclusions:There were no significant differences in the duration of CMV infection, incidence of CMV disease, rate of recurrence of CMV infection, and survival of the patients treated with the combination of antiviral drugs and a single antiviral drug.

Analysis of clinicopathological characteristics, therapeutic strategy and prognosis of 501 patients with gastric neuroendocrine neoplasms attending a single center / 中华胃肠外科杂志

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.

Advances in Phytochemistry and Modern Pharmacology of Saposhnikovia Divaricata (Turcz.) Schischk / 中国结合医学杂志

Saposhnikovia divaricata (Turcz.) Schischk (S. divaricata, Fangfeng) is a herb in the Apiaceae family, and its root has been used since the Western Han Dynasty (202 B.C.). Chromones and coumarins are the pharmacologically active substances in S. divaricata. Modern phytochemical and pharmacological studies have demonstrated their antipyretic, analgesic, anti-inflammatory, antioxidant, anti-tumor, and anticoagulant activities. Technological and analytical strategy theory advancements have yielded novel results; however, most investigations have been limited to the main active substances-chromones and coumarins. Hence, we reviewed studies related to the chemical composition and pharmacological activity of S. divaricata, analyzed the developing trends and challenges, and proposed that research should focus on components' synergistic effects. We also suggested that, the structure-effect relationship should be prioritized in advanced research.

Near-infrared targeted probe designed for intraoperative imaging of prostatic neurovascular bundles / 北京大学学报(医学版)

OBJECTIVE@#To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats.@*METHODS@#A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowⅡ(NIR-Ⅱ) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures.@*RESULTS@#Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-Ⅱ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) μm. HE staining of paraffin sections showed the right major pelvic ganglion.@*CONCLUSION@#The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.

Re-evaluation of systematic reviews of acupuncture and moxibustion for childhood autism / 中国针灸

OBJECTIVE@#To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment.@*METHODS@#The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence.@*RESULTS@#A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias.@*CONCLUSION@#Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.

Mechanism of Polygonum capitatum in treatment of Helicobacter Pylori associated gastritis by network pharmacology, microarray data analysis and molecular docking / 中国药理学通报

Aim To explore the mechanism of Polygonum capitatum(PC)in the treatment of Helicobacter Pylori associated gastritis(HAG). Methods The databases were used to identify the target of PC active compounds and HAG-related genes,and the intersection was taken to obtain the potential targets of PC treatment of HAG. The interaction network diagram of “drug-active compound-target-disease” and the protein-protein interaction(PPI)network of potential target protein interaction in HAG treated by PC were constructed by software Cytoscape 3.6.0. The important nodes in the network were screened by several topological indexes,and the GO and KEGG enrichment were analyzed by STRING database to obtain the potential signaling pathway of PC in the treatment of HAG. The binding ability of PC active components with key target proteins was observed by molecular docking method. On this basis,the related targets of PC in the treatment of HAG were verified in vivo and in vitro experiments. Results The PC active compounds and targets were identified through the database,and the “drug-active compound-target-disease” network diagram and the PPI network of potential target proteins were constructed. Combined with several topological indexes,the PPI network of potential target-protein interaction was analyzed,and 52 hub genes were screened. Further bioinformatics analysis and high-throughput sequencing revealed that PC exerted an effect on HAG through the Akt/NF-κB/NLRP3 pathway. Based on this,it was found that PC could reduce IL-18 and IL-1β in HAG GES-1 cells and HAG SD rats,up-regulate Akt and its phosphorylation level and reduce NF-κB expression,inhibit the activation of NLRP3 inflammatory body,so as to improve HAG inflammatory response. Conclusions PC could exert a therapeutic effect on HAG by activating Akt and its phosphorylation level,and inhibiting the expression of NF-κB and NLRP3 inflammasome related factors. This study provides a theoretical basis for explaining the mechanism of PC in the treatment of HAG.

Impact of SARS-CoV-2 infection on graft composition and early transplant outcomes following allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.

Clinical significance of Epstein-Barr Virus detection in the cerebrospinal fluid of patients who underwent hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the detection rate, clinical significance, and prognosis of Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of patients following allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis was performed on 1100 patients who underwent the CSF virus test after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital between January 2017 and June 2022. Among them, 19 patients were screened positive for EBV in their CSF, and their clinical characteristics, treatment, and prognosis were analyzed. Results: Among 19 patients with EBV-positive cerebrospinal fluid, 12 were male and 7 were female, with 5 patients aged <18 years and 12 aged ≥18 years, with a median age of 27 (5-58) years old. There were 7 cases of acute myeloid leukemia, 8 of acute lymphocytic leukemia, 2 of aplastic anemia, 1 of Hodgkin's lymphoma, and 1 of hemophagocytic syndrome. All 19 patients underwent haploid hematopoietic stem cell transplantation, including 1 secondary transplant. Nineteen patients had neurological symptoms (headache, dizziness, convulsions, or seizures), of which 13 had fever. Ten cases showed no abnormalities in cranial imaging examination. Among the 19 patients, 6 were diagnosed with EB virus-related central nervous system diseases, with a median diagnosis time of 50 (22-363) days after transplantation. In 9 (47.3%) patients, EBV was detected in their peripheral blood, and they were treated with intravenous infusion of rituximab (including two patients who underwent lumbar puncture and intrathecal injection of rituximab). After treatment, EBV was not detected in seven patients. Among the 19 patients, 2 died from EBV infection and 2 from other causes. Conclusion: In patients who exhibited central nervous system symptoms after allogeneic hematopoietic stem cell transplantation, EBV should be screened as a potential pathogen. EBV detected in the CSF may indicate an infection; however, it does not confirm the diagnosis.

Gene expression and immunolocalization of chitin deacetylase BmCDA2 in silkworm / 生物工程学报

Deacetylation of chitin is closely related to insect development and metamorphosis. Chitin deacetylase (CDA) is a key enzyme in the process. However, to date, the CDAs of Bombyx mori (BmCDAs), which is a model Lepidopteran insect, were not well studied. In order to better understand the role of BmCDAs in the metamorphosis and development of silkworm, the BmCDA2 which is highly expressed in epidermis was selected to study by bioinformatics methods, protein expression purification and immunofluorescence localization. The results showed that the two mRNA splicing forms of BmCDA2, namely BmCDA2a and BmCDA2b, were highly expressed in the larval and pupal epidermis, respectively. Both genes had chitin deacetylase catalytic domain, chitin binding domain and low density lipoprotein receptor domain. Western blot showed that the BmCDA2 protein was mainly expressed in the epidermis. Moreover, fluorescence immunolocalization showed that BmCDA2 protein gradually increased and accumulated with the formation of larval new epidermis, suggesting that BmCDA2 may be involved in the formation or assembly of larval new epidermis. The results increased our understandings to the biological functions of BmCDAs, and may facilitate the CDA study of other insects.

The use of melittin to enhance transgene expression mediated by recombinant adeno-associated virus serotype 2 vectors both in vitro and in vivo / 中西医结合学报

OBJECTIVE@#Melittin, a cell-penetrating peptide, improves the efficiency of many non-viral gene delivery vectors, yet its application in viral vectors has not been well studied. The non-pathogenic recombinant adeno-associated virus (rAAV) vector is an ideal in vivo gene delivery vector. However, its full potential will only be achieved after improvement of its transduction efficiency. To improve the transduction efficiency of rAAV2 vectors, we attempted to develop a melittin-based rAAV2 vector delivery strategy.@*METHODS@#The melittin peptide was inserted into the rAAV2 capsid either in the loop VIII of all viral proteins (VPs) or at the N terminus of VP2. Various rAAV2-gfp or -fluc vectors were subjected to quantitative real-time polymerase chain reaction and Western blot assays to determine their titers and integrity of capsid proteins, respectively. Alternatively, the vectors based on wild-type capsid were pre-incubated with melittin, followed by transduction of cultured cells or tail vein administration of the mixture to C57BL/6 and BALB/c nude mice. In vivo bioluminescence imaging was performed to evaluate the transgene expression.@*RESULTS@#rAAV2 vectors with melittin peptide inserted in the loop VIII of VPs had low transduction efficiency, probably due to dramatically reduced ability to bind to the target cells. Fusing the melittin peptide at the N-terminus of VP2 produced vectors without the VP2 subunit. Interestingly, among the commonly used rAAV vectors, pre-incubation of rAAV2 and rAAV6 vectors with melittin significantly enhanced their transduction efficiency in HEK293 and Huh7 cells in vitro. Melittin also had the ability to increase the rAAV2-mediated transgene expression in mouse liver in vivo. Mechanistically, melittin did not change the vector-receptor interaction. Moreover, cell counting kit-8 assays of cultured cells and serum transaminase levels indicated melittin had little cytotoxicity.@*CONCLUSION@#Pre-incubation with melittin, but not insertion of melittin into the rAAV2 capsid, significantly enhanced rAAV2-mediated transgene expression. Although further in vivo evaluations are required, this research not only expands the pharmacological potential of melittin, but also provides a new strategy to improve gene therapy mediated by rAAV vectors.

Establishment and validation of a nomogram for predicting prognosis of gastric neuroendocrine neoplasms based on data from 490 cases in a single center / 南方医科大学学报

OBJECTIVE@#To develop and validate a nomogram for predicting outcomes of patients with gastric neuroendocrine neoplasms (G-NENs).@*METHODS@#We retrospectively collected the clinical data from 490 patients with the diagnosis of G-NEN at our medical center from 2000 to 2021. Log-rank test was used to analyze the overall survival (OS) of the patients. The independent risk factors affecting the prognosis of G-NEN were identified by Cox regression analysis to construct the prognostic nomogram, whose performance was evaluated using the C-index, receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, DCA, and AUDC.@*RESULTS@#Among the 490 G-NEN patients (mean age of 58.6±10.92 years, including 346 male and 144 female patients), 130 (26.5%) had NET G1, 54 (11.0%) had NET G2, 206 (42.0%) had NEC, and 100 (20.5%) had MiNEN. None of the patients had NET G3. The numbers of patients in stage Ⅰ-Ⅳ were 222 (45.3%), 75 (15.3%), 130 (26.5%), and 63 (12.9%), respectively. Univariate and multivariate analyses identified age, pathological grade, tumor location, depth of invasion, lymph node metastasis, distant metastasis, and F-NLR as independent risk factors affecting the survival of the patients (P < 0.05). The C-index of the prognostic nomogram was 0.829 (95% CI: 0.800-0.858), and its AUC for predicting 1-, 3- and 5-year OS were 0.883, 0.895 and 0.944, respectively. The calibration curve confirmed a good consistency between the model prediction results and the actual observations. For predicting 1-year, 3-year and 5-year OS, the TNM staging system and the nomogram had AUC of 0.033 vs 0.0218, 0.191 vs 0.148, and 0.248 vs 0.197, respectively, suggesting higher net benefit and better clinical utility of the nomogram.@*CONCLUSION@#The prognostic nomogram established in this study has good predictive performance and clinical value to facilitate prognostic evaluation of individual patients with G-NEN.

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup / 中国结合医学杂志

OBJECTIVE@#To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients.@*METHODS@#By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup.@*RESULTS@#Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens.@*CONCLUSIONS@#There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

Nocturnal hypertension and riser pattern are associated with heart failure rehospitalization in patients with heart failure with preserved ejection fraction / 老年心脏病学杂志（英文版）

BACKGROUND@#Nocturnal hypertension is reported as a risk factor for cardiovascular disease. This study aimed to explore the potential association between nocturnal hypertension and heart failure (HF) rehospitalization in patients with HF with preserved ejection fraction (HFpEF).@*METHODS@#A total of 538 patients with HFpEF from May 2018 to December 2021 were consequently recruited in this study and followed up until they were readmitted for HF or the end of this study. Cox regression analysis was used to reveal the potential association between nighttime blood pressure (BP) levels, nocturnal hypertension and nocturnal BP patterns and HF rehospitalization. Kaplan-Meier curve was used to assess the cumulative event-free survival rate between groups.@*RESULTS@#There were 537 patients with HFpEF were included in the final analysis. The mean age of the study population was 77.14 ± 8.68 years, and 41.2% of patients were men. After a median follow-up duration of 10.93 (4.19-21.13) months, 176 patients (32.7%) with HFpEF were readmitted for HF. Cox regression analysis had revealed that nighttime systolic BP level [hazards ratio (HR) = 1.018, 95% CI: 1.008-1.028, P = 0.001], nighttime diastolic BP level (HR = 1.024, 95% CI: 1.007-1.042, P = 0.007), nocturnal hypertension (HR = 1.688, 95% CI: 1.229-2.317, P = 0.001) were associated with HF rehospitalization. Kaplan-Meier analysis had demonstrated that patients with nocturnal hypertension had significantly lower event-free survival rate (log-rank P < 0.001). Furthermore, patients with a riser pattern had a higher risk of HF rehospitalization (HR = 1.828, 95% CI: 1.055-3.166, P = 0.031) and lower event-free survival rate (log-rank P = 0.003) than those with a dipper pattern. These findings were also confirmed in patients with HFpEF and hyperuricemia.@*CONCLUSIONS@#Nighttime BP levels, nocturnal hypertension and a riser pattern are independently associated with HF rehospitalization in patients with HFpEF, and prominently in patients with HFpEF and hyperuricemia. Well controlled nighttime BP levels should be emphasized and considered in patients with HFpEF.

Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.

Effect of long-term combination anti-retroviral therapy on cardiovascular disease risks in human immunodeficiency virus/acquired immunodeficiency syndrome patients / 中华传染病杂志

Objective:To explore the risks of cardiovascular disease (CVD) and influencing factors in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients with long-term combination anti-retroviral therapy (cART).Methods:The baseline data from the multi-center prospective cohort of HIV/AIDS patients who received long-term cART from 2018 to 2020 were collected. cART-naive HIV/AIDS patients were matched by age and gender using the propensity score matching (PSM) as controls. Data collection adverse events of anti-human immunodeficiency virus drugs reduced model (D: A: D[R]) score, Framingham risk score (FRS) and atherosclerotic cardiovascular disease (ASCVD) risk score were used to assess the 10-year CVD risk in patients with long-term cART treatment and in cART-naive patients. Logistic regression analysis was used to assess the risk factors related to high 10-year CVD risk.Results:A total of 301 HIV/AIDS patients received long-term cART and 300 cART-naive HIV/AIDS patients were included, with an average age of 39.8 years old. There were 490 male accounting for 81.5%. Based on the D: A: D [R] score, 4.3%(13/301) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥10%, and 6.3%(19/300) of patients in the cART-naive group. Based on the FRS, 13.4%(36/269) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥10%, and 10.6%(28/264) in the cART-naive group. Based on the ASCVD risk score, 10.4%(14/135) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥7.5%, and 13.8%(17/123) in the cART-naive group. There was no significant difference in the prevalence of high 10-years CVD risk between the long-term cART group and the cART-naive group assessed by any of risk equations (all P>0.050). By multivariate logistic regression analysis, the risk factors associated with 10-year CVD risk ≥10% assessed by D: A: D[R] model were age≥50 years, smoking, hypertension, diabetes, dyslipidemia and CD4 + T lymphocyte count <200×10 6 cells/L (adjusted odds ratio ( AOR)=697.48, 4 622.28, 23.11, 25.95, 27.72 and 18.25, respectively, all P<0.010). The risk factors associated with 10-year CVD risk ≥10% assessed by FRS were age≥50 years, male, smoking, hypertension, diabetes and dyslipidemia ( AOR=53.51, 4.52, 36.93, 36.77, 6.15 and 3.84, respectively, all P<0.050). The risk factors associated with 10-year CVD risk ≥7.5% assessed by ASCVD risk score were age≥50 years, male, smoking, hypertension, diabetes ( AOR=18.48, 14.11, 14.81, 13.42 and 12.41, respectively, all P<0.050). Conclusions:Long-term cART has no significant effect on the 10-year CVD risk in HIV/AIDS patients. Higher CVD risk in HIV/AIDS patients are mainly associated with CD4 + T lymphocyte counts<200×10 6 cells/L and traditional CVD risk factors, including age≥50 years old, smoking, hypertension, diabetes and dyslipidemia.

Establishment of ultrasound-guided incomplete ablation model of ectopic implanted tumor of liver cancer in nude mice / 中华超声影像学杂志

Objective:To establish a good model of incomplete ablation of ectopic implanted tumor of liver, and explore the changes in the molecular landscape of residual cancer, cancer in nude mice.Methods:Eight immunodeficient BALB/c nude mice were used to establish an ectopic tumor model with the MHCC97-H hepatoma cell line, and they were randomly divided into experimental group and control group, with 4 mice in each group. The experimental group underwent simulated clinical incomplete ablation, and the control group only underwent false ablation. The differences between the models were evaluated by ultrasonic diagnostic equipment, thermal imaging cameras, HE staining and high-throughput whole transcriptome sequencing.Results:Liver cancer ectopic implantations in nude mices were all successful. The experimental group showed that the temperature of the tumor around the tip of the needle monitored by the thermal imaging camera was at 50-73.9 ℃. Compared with the control group, the HE staining of the experimental group mostly showed the coexistence of necrotic area-degeneration area-tumor cell area. The necrosis area was (23.75±13.77)%, and the degeneration area was 50%(30%). High-throughput whole transcriptome sequencing revealed that there were hundreds of overlapping stable molecular landscapes in the incomplete ablation simulation model both in vivo and in vitro.Conclusions:By establishing an ectopic implantion model of nude mice with incomplete ablation of residual liver cancer, it can provide a basis for studying the biological characteristics of incomplete ablation of residual cancer at the molecular level.

Effect of all-trans retinoic acid on maturation and differentiation of mouse hepatic progenitor cells induced by bone morphogenetic protein 9 and its mechanism / 解剖学报

Objective To investigate the effect of 1 μmol/L and 10 μmol/L all trans retinoic acid（ATRA） on bone morphogenetic protein 9（BMP9）-induced maturation and differentiation of hepatic progenitor cells. Methods BMP9, BMP9 + 1 μmol/L ATRA and BMP9 + 10 μmol/L ATRA acted on HP14-19, respectively. The expression of albumin-drive gussid（LAB-Glus） was detected by luciferase reporter gene. The mRNA levels of ALB, cytokeratin 18（CK18）, tyrosine aminotransferase（TAT）, apolipoprotein B（ApoB） were detected by Real-time PCR. The expressions of ALB and uridine diphosphate glucuronosyltransferase 1 A（UGT1 A） were detected by immunofluorescence. Periodic acid-schiff（PAS） staining and indocyanine green（ICG） uptake assay were used to detect the metabolism and glycogen synthesis of hepatocytes. Real-time PCR and Western blotting were used to detect the expression of retinoic acid receptor（RAR）α, RARβ、RARγ and BMP9 signal related molecules Samd1, Samd 5 and Samd 8. Ad-siRARα、Ad-siRARβ、Ad-siRARγ infected cells were treated with BMP9+10 μmol/L ATRA, the cell morphology and PAS staining result were observed, the mRNA levels of ALB, CK18, TAT and ApoB were detected by Real-time PCR. Results BMP9 could significantly induce the maturation and differentiation of HP14-19 cells. The morphology of HP14-19 cells looked like polygonal paving stone. The expressions of ALB, CK18, ApoB and UGT1 A were significantly up-regulated. Some cells had the function of metabolic detoxification and glycogen synthesis. Compared with the BMP9 group, BMP9+1 μmol/L ATRA group had more mature morphology and larger volume. The expressions of Alb, CK18, ApoB and UGT1 A were up-regulated significantly（P＜0.05）. The number of ICG and PAS positive cells increased. Compared with the BMP9+1 μmol/L ATRA group, BMP9 + 10 μmol/L ATRA group showed long spindle, spindle and polygonal shapes, and the expression of hepatocyte related markers decreased, and the number of ICG and PAS positive cells decreased. ATRA（1 μmol/L） significantly increased the expression of RARα, RARβ and RARγ. Compared with the 1 μmol/L ATRA group, 10 μmol/L ATRA group only increased the expression of RARα. BMP9 did not affect the expression levels of Samd1, Samd5 and Samd8, but up-regulated their phosphorylation. Ad-siRARα could improve cell morphology and PAS staining induced by 10 μmol/L ATRA, while increased the expression of Alb and CK18（P＜0.05）. Conclusion ATRA（1 μmol/L） can promote the maturation and differentiation of hepatic progenitor cells（HPCs） induced by BMP9, while 10 μmol/L ATRA can weaken the differentiation of hepatic progenitor cells. Excessive ATRA may over activate RARα signal to affect the differentiation of hepatic progenitor cells.

Recent progress of nanoparticle-enabled modulation of macrophages for cancer immunotherapy / 药学学报

Macrophages play an important role in maintaining homeostasis of the body, and they are also one of the most abundant immune cells in the tumor microenvironment (TME). These macrophages are often called tumor-associated macrophages (TAMs), which play an important role in the development of tumor and are an important target for tumor therapy. Studies have shown that tumor growth and metastasis can be inhibited by regulating the function of macrophages, but the therapeutic efficacy was often hampered by the poor performance of the drugs such as lack of targeting, poor solubility, low bioavailability, and severe side effects. After introduction of the background of macrophage and tumor therapy, this review focuses on the research progress of nano-drug delivery systems in the modulation of the function of macrophages to enhance tumor immunotherapy. Nano-drug delivery systems are diverse in structures and functions, and can regulate macrophage functions through a variety of mechanisms. Four important aspects of macrophage modulation, which included TAMs depletion, repolarization of TAMs, promoted phagocytosis of TAMs, and combinational modulation of TAMs were summarized. Each strategy together with typical examples was reviewed and future directions in this field were also prospected.

Effect of Qinggan Zishen Prescription on Metabolic Disorder in Obesity-related Hypertension and Its Mechanism Based on Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo explore the effect of Qinggan Zishen prescription on metabolic disorders in obesity-related hypertension （OBH） patients and analyze the potential pharmacological mechanism based on network pharmacology. MethodA total of 85 eligible OBH patients who were treated in the outpatient or wards of Jiangsu Province Hospital of Chinese medicine from September 2018 to January 2020 were selected and randomized into the observation group （45 cases） and control group （40 cases）. All patients were treated with western medicine during a four-week introduction period， and then the observation group was treated with Qinggan Zishen prescription on the basis of western medicine. The study lasted 6 months， and indicators， such as triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， glycosylated hemoglobin （HbA1c）， fasting blood glucose （FBG）， fasting insulin （FINS）， waist circumference （W）， hip circumference （H） were detected and homeostasis model assessment of insulin resistance （HOMA-IR），body mass index （BMI）， waist-hip ratio （WHR） were calculated before and after intervention. At the same time， the regulation network of the Qinggan Zishen prescription was visualized and the protein-protein interaction （PPI） network was constructed. The core targets of the network were obtained for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. ResultAfter intervention for 6 months， the levels of W， H， WHR， FINS， and HOMA-IR in the observation group were reduced as compared with those in the control group （P<0.05， P<0.01）. According to network pharmacology， the main components of Qinggan Zishen prescription in treating OBH were luteolin， quercetin， and berberine and the key targets were amyloid precursor protein （APP）， vascular endothelial growth factor A （VEGFA）， and estrogen receptor 1 （ESR1）. Moreover， the key biological pathway was advanced glycation end product （AGE）/advanced glycation end product receptor （RAGE） signaling pathway. ConclusionQinggan Zishen prescription can improve the metabolic disorder of OBH patients through multiple components， multiple targets， and multiple pathways， which provides new mindset for follow-up studies.

Review and updates on physical activity load assessment in preschool children / 中国学校卫生

Abstract@#With the increasing attention paid to preschool physical activity in recent years, physical activity load assessment of preschool children has evolved with the development of theory and the wide application of microelectronic technology. In this paper, relevant literature from PubMed, Web of Science, and CNKI database were collected and analyzed, aiming to provide review and updates on physical activity load assessment in preschoolers. Given the characteristics of children s physical activities, effective measurement methods should be chosen and integrated from these tools, to improve the accuracy and effectiveness of children s physical activity load assessment.