Objective : To investigate the epidemiological characteristics of influenza among the elderly in Heilongjiang Province from 2017 to 2021 (April 2017 to March 2022), so as to provide insights into influenza control among the elderly. Methods : The data pertaining to surveillance of patients with influenza-like illness (ILI) at ages of 60 years and older in Heilongjiang Province from 2017 to 2021 were retrieved from Chinese Influenza Surveillance Information Management, and the temporal distribution of ILI cases and the results of influenza virus tests were descriptively analyzed. Results : Totally 26 908 ILI cases at ages of 60 years and older were reported in Heilongjiang Province from 2017 to 2021, with an ILI prevalence rate of 0.17%. The prevalence of ILI appeared a tendency towards a rise in Heilongjiang Province from 2017 to 2021 (χ2trend=268.554, P<0.001), and the epidemic peaked in the 3rd to 7th weeks of 2019 and 2020. The overall positive rate of influenza virus was 6.80%, and the positive rate of influenza virus showed a tendency towards a decline from 2017 to 2021 (χ2trend=425.268, P<0.001). Influenza A (H1N1) pdm09 (46.82%) and A (H3N2) (22.79%), as well as influenza B virus lineages B/Victoria (12.11%) and B/Yamagata (18.28%) were predominant types, which changes among the study period. The detection of influenza virus-positive samples peaked from December to March of the next year, and a high positive rate of influenza virus was detected in Hegang (12.35%), Heihe (11.47%) and Daqing cities (11.07%). There was no significant correlation between the prevalence of ILI and the positive rate of influenza virus in Heilongjiang Province from 2017 to 2021 (rs=-0.800, P=0.104). Conclusions The prevalence of ILI appeared a tendency towards a rise among the elderly at ages of 60 years and older in Heilongjiang Province from 2017 to 2021, and the epidemic peaked in winter and spring. Influenza A (H1N1) pdm09, A (H3N2), B/Victoria, B/Yamagata were alternately prevalent and there was no obvious correlation between ILI prevalence and the positive rate of influenza virus.

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
China ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Prescriptions ; Public Health

Pediatric medication in China is characterized by a lack of child-specific drugs and insufficient types, specifications, dosage forms, and delivery devices. In recent years, new dosage forms with good compliance, such as inhalation preparation, rectal delivery system, and transdermal delivery system, have attracted more attention in pediatric medication. Because of the physiological characteristics of delicate viscera, difference in swallowing ability and psychological characteristics of fear of pain and aversion to bitter taste, it is particularly important to select suitable drug delivery route and drug delivery device according to children's physiological characteristics. With the help of the special drug delivery devices, traditional Chinese medicine and innovative Chinese medicine can be administered according to the expected design path, and drug delivery devices can ensure the accurate dose and improve the complia-nce to achieve the purpose of effective and safe drug delivery. It is also a way to realize the re-innovation of traditional Chinese medicine. The present study summarized the research progress in drug delivery devices for common drug delivery routes and new drug deli-very routes, put forward the innovative design idea of children's drug delivery devices according to the special needs of children, poin-ted out the compatibility of drug delivery devices and other problems in the current development, and prospected the application of intelligent information technology and additive manufacturing technology in drug delivery device innovation. This is expected to provide references for the development of innovative drugs and drug delivery devices suitable for children's multidimensional demand for medication.
Child ; Humans ; Pharmaceutical Preparations ; Medicine, Chinese Traditional ; Drug Delivery Systems ; China

OBJECTIVE: To establish the droplet digital PCR (ddPCR) assay for the detection of NPM1 type A mutation in patients with acute myeloid leukemia (AML), and to evaluate its specificity, sensitivity and its value in clinical application. METHODS: NPM1 mutant and wildtype plasmids were used to verify the performance of ddPCR. Both ddPCR and Sanger sequencing were used to detect the bone marrow samples of 87 AML patients, which were confirmed by next generation sequencing (NGS). Moreover, NPM1 mutation burden was dynamically monitored in five patients by ddPCR. RESULTS: The limit of blank (LOB) of ddPCR established for NPM1 mutation detection was 1.1 copies/μl, and the limit of detection (LOD) was 2.43 copies/μl, which had good linearity. Among the 87 newly diagnosed AML patients, ddPCR identified seventeen cases positive for NPM1 mutation (19.5%)， which was consistent with Sanger sequencing. NGS confirmed 12 positive cases, including 8 of type A mutations, 2 of type D mutations, and 2 of rare type mutations. The results of dynamic monitoring of NPM1 mutation burden in 5 patients showed that the NPM1 mutation burden decreased obviously even close to 0, when patients achieve complete remission after chemotherapy. However, the mutation burden was increased again at the time of relapse. CONCLUSION In this study, we established a ddPCR method for detection of NPM1 mutation with good sensitivity and repeatability, which can be used for screening NPM1 mutation in newly diagnosed AML patients and for minimal residual disease monitoring after remission in positive AML patients to guide treatment.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Mutation ; Nuclear Proteins/genetics* ; Nucleophosmin ; Polymerase Chain Reaction ; Prognosis

: AbstractObjective: To identify the expression and methylation patterns of lncRNA CASC15 in bone marrow (BM) samples of acute myeloid leukemia (AML) patients, and further explore its clinical significance. METHODS: Eighty-two de novo AML patients and 18 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the expression and methylation data of CASC15. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of CASC15 expression to identify AML. The patients were divided into CASC15high group and CASC15low group by X-tile method, and the prognostic value of CASC15 was identified by Kaplan-Meier method and univariate and multivariate Cox regression analysis. RESULTS: The expression level of CASC15 was significantly decreased in BM cells of AML patients compared with healthy donors (P<0.001). ROC curve analysis suggested that CASC15 expression might be a potential biomarker to discriminate AML from controls. The expression of CASC15 was high at the early stage of hematopoiesis, and reached a peak at the stage of multipotent progenitors differentiation, then decreased rapidly, and was at a range of low level fluctuations in the subsequent process. Among FAB subtypes, CASC15 expression in M0 was significantly higher than that in M1-M7. Clinically, CASC15low patients were more likely to have NPM1 mutations than CASC15high patients (P=0.048), while CASC15high patients had a significantly higher frequency of IDH1 and RUNX1 mutations (P=0.021 and 0.014, respectively). Moreover, CASC15low group had a shorter overall survival (OS) in patients with NPM1 mutations. Furthermore, multivariate analysis confirmed that CASC15 expression was a significant independent risk factor for OS in NPM1 mutated AML patients. In addition, CASC15 methylation level in BM samples of AML patients was significantly decreased compared with healthy donors. Patients with CASC15 high methylation had poor OS and disease-free survival. CONCLUSION The expression of CASC15 is decreased in AML, and low CASC15 expression may predict adverse prognosis in AML patients with NPM1 mutations. Moreover, CASC15 methylation level in AML is significantly decreased, and high CASC15 methylation may predict poor prognosis in AML.
Humans ; Leukemia, Myeloid, Acute/metabolism* ; Mutation ; Nuclear Proteins/genetics* ; Nucleophosmin/genetics* ; Prognosis ; RNA, Long Noncoding/genetics*

OBJECTIVE: To assess the clinical effectiveness of acupoint application (AP) of Guan Xin Su He Pill (, GXSHP) for patients with chronic stable angina pectoris (CSAP). METHODS: This study was carried out in 3 local hospitals in Chengdu, China. After baseline evaluation, eligible patients were randomly assigned to the placebo application for acupoints (PAA) group or the herbal application for acupoints (HAA) group. Patients in the HAA group underwent AP with herbal powder, which was mainly GXSHP, and patients in the PAA group underwent AP with sham drugs. For each treatment session, unilateral acupoints including Neiguan (PC 6), Danzhong (RN 17), Xinshu (BL 15) and Jueyinshu (BL 14), were stimulated for both groups. AP was performed 3 times a week with a 2-day interval for 4 weeks. The primary outcome was the frequency of angina pectoris attacks per week, while the secondary outcomes included angina pain intensity measured by the Visual Analogue Scale (VAS), dose of rescue oral drugs (nitroglycerin), scores on the Seattle Angina Questionnaire (SAQ), Self-Rating Anxiety Scale scores (SAS) and Self-Rating Depression Scale scores (SDS). Clinical outcomes were measured at week 0, 4 and 8. The safety of AP of GXSHP treatment for CSAP were assessed. RESULTS: A total of 121 patients were enrolled. Baseline characteristics were comparable across the 2 groups. After treatment, the angina attack numbers in the HAA group were significantly reduced from 11.00 to 4.81 (P<0.05). While, for PAA group, the angina frequency was not significantly improved (baseline 10.55; post-treatment 11.05). The HAA group had significantly fewer angina attacks than the PAA group (P<0.05). Pain intensity measured by VAS in HAA group was significantly reduced from 4.06 to 3.02 (P<0.05). While, for PAA group, the VAS was significantly increased (baseline 3.62; post-treatment 3.96; P<0.05). Clinical outcomes showed better improvement after treatment in the HAA group than in the PAA group in terms of oral administration of rescue drugs, SAS, SDS and SAQ scores (P<0.05). The adverse events were also reported. CONCLUSION AP of GXSHP is a safe and effective treatment for CSAP patients (Registration No. NCT02029118).
Acupuncture Points ; Angina, Stable/drug therapy* ; China ; Drugs, Chinese Herbal/adverse effects* ; Female ; Humans ; Male ; Treatment Outcome

Background:Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD).The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:This is an 8-week,double-blind,randomized,placebo-controlled study.Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min,77.5-Hz,15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4),following a 4-week observation period (week 8).The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8.Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17,the proportion of participants having improvement in the clinical global impression-improvement,the change in HDRS-17 score (range,0-52,with higher scores indicating more depression) over the study,and variations of brain imaging and neurocognition from baseline to week 4.Safety will be assessed by vital signs at weeks 4 and 8,and adverse events will be collected during the entire study.Discussion:The tACS applied in this trial may have treatment effects on MDD with minimal side effects.

BackgroundEndometriosis is a challenging disease with symptoms such as dysmenorrhea and infertility. However, its etiology is still vague and there is still no effective markers or treatment. This study aimed to profile the circular RNAs (circRNAs) expressed in eutopic endometrium from patients with ovarian endometriosis and explore potential clues to the pathogenesis of endometriosis, providing an evidence for clinical diagnosis and treatment.

MethodsA total of 63 clinical samples, including control endometrium (n = 22) and eutopic endometrium (n = 41), were collected from Peking Union Medical College Hospital between May 1, 2016, and December 31, 2016. Of them, four samples in each group were used for circRNA microarray. Then, four upregulated circRNAs were screened out for quantitative real-time polymerase chain reaction (qRT-PCR) validation. After that, bioinformatics analysis was performed to predict miRNAs targeted by validated circRNAs and investigate the circRNA-miRNA-mRNA interactions.

ResultsAmong 88 differentially expressed circRNAs, 11 were upregulated and 77 were downregulated in eutopic endometrium of patients with endometriosis. qRT-PCR validation results for two upregulated circRNAs (circ_0004712 and circ_0002198) matched the microarray results. The area under the receiver operating characteristic curve of circ_0002198 for distinguishing ovarian endometriosis was 0.846 (95% confidence interval [CI]: 0.752-0.939; P < 0.001) while that of circ_0004712 was 0.704 (95% CI: 0.571-0.837; P = 0.008). On the basis of target prediction, we depicted the molecular interactions between the identified circRNAs and their dominant target miRNAs, as well as constructed a circRNA-miRNA-mRNA network.

ConclusionsThis study provides evidence that circRNAs are differentially expressed between eutopic and normal endometrium, which suggests that circRNAs are candidate factors in the activation of endometriosis. circ_0002198 and circ_0004712 may be potential novel biomarkers for the diagnosis of ovarian endometriosis.

Objective: To study the molecular characteristics of norovirus in 4 outbreaks of gastroenteritis in Heilongjiang province in 2016. Methods: Fecal specimens of patients were collected from 4 outbreaks of acute viral gastroenteritis. Real-time PCR was performed to identify the infection with Norovirus (NoV). The NoV genes were amplified and sequenced for the positive samples, followed by performing phylogenetic analysis. Results: There were total 4 outbreaks of viral gastroenteritis caused by NoV. A total of 102 stool specimens were obtained from cases with acute gastroenteritis. NoV was detected in 35 cases including 14 strains of genogroup I NoV and 21 strains of genogroup II NoV. Six genotypes including GII.2, GII.17, GII.Pe, GII.P12/GII.3, GI.6, GI.Pd/GI.3 were detected. Conclusions NoV was the pathogen causing the gastroenteritis outbreaks in Heilongjiang province, and multigenotype NoV co-circulated in Heilongjiang province.

OBJECTIVETo compare the prognostic value of different models in patients with early-stage diffuse large B-cell lymphoma (DLBCL).

METHODSEarly-stage DLBCL patients diagnosed from January 2000 to December 2012 were analyzed retrospectively. All patients received with at least 2 cycles of immunochemotherapy R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with or without radiotherapy. The prognostic value of international prognostic index (IPI) , revised IPI (R-IPI) and enhanced IPI (NCCN-IPI) was compared.

RESULTSNinety-seven cases of early-stage DLBCL were included in the study. The median age was 58 years (15-88 years) with a median follow-up of 34.7 months (range 7.3-77.4 months). The expected 5-year overall survival (OS) for entire group was 82%. There was no patient in the high risk group according to IPI or NCCN-IPI. According to IPI, the 5-year OS in the low, low intermediate, high intermediate risk groups were 95%, 38% and 60%, respectively. According to R-IPI, the 5-year OS in the very good, good, and poor risk groups were 93%, 75% and 60%, respectively. According to NCCN-IPI, the 5-year OS in the low, low intermediate, high intermediate risk groups were 92%, 85% and 29%, respectively.

CONCLUSIONNCCN-IPI would be of an ideal prognostic model for early-stage DLBCL patients.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Combined Chemotherapy Protocols ; Cyclophosphamide ; Doxorubicin ; Humans ; Immunotherapy ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; Middle Aged ; Prednisone ; Prognosis ; Retrospective Studies ; Rituximab ; Vincristine ; Young Adult