[Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions].

The group standard Guidelines for construction of traditional Chinese medicine(TCM) pharmacovigilance system in medical institutions, managed by Chinese Association of Chinese Medicine and led by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences and Dongfang Hospital of Beijing University of Chinese Medicine, was announced on National Group Standard Information Platform on January 16, 2024, with the standard number T/CACM 1563. 2-2024. According to EU pharmacovigilance regulations and the second-level guidance principles of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), the unique characteristics of TCM were fully considered, and the relevant systems and procedures for constructing TCM pharmacovigilance systems in medical institutions were clearly defined. This included establishing TCM pharmacovigilance information platforms, arranging staff, formulating various regulations, and monitoring adverse reactions of TCM(including TCM decoction pieces, granules, Chinese patent medicines, in-hospital preparations, and pre-marketed Chinese patent medicines). It aimed to develop a TCM pharmacovigilance system in medical institutions that was tailored to the characteristics of TCM. The system could be appropriately adjusted according to the scope of practice and actual circumstances of medical institutions at different levels. This will enhance the implementation of TCM pharmacovigilance work and safeguard medication safety. The group standard underwent multiple rounds of consultations with internal and external experts and has ultimately evolved into a guiding document applicable to medical institutions and related entities engaged in pharmacovigilance activities.

[Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines].

Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

[Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections].

In 2019, the newly revised Drug Administration Law of the People's Republic of China was issued and implemented,clearly proposing that China should establish a pharmacovigilance system. As a new traditional Chinese medicine(TCM) dosage form created in China, TCM injections have been widely used in clinic, and its pharmacovigilance has attracted much attention. In response to this situation, the project team convened a group of clinical, pharmaceutical and evidence-based medicine experts from all over the country to form an expert group, which formulated the Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections in strict accordance with the requirements of the group standards of the Chinese Association of Chinese Medicine.From the perspective of clinical application and considering the key elements of pharmacovigilance for clinical application of TCM injections, the guidelines put forward suggestions on the decision making of pharmacovigilance for clinical application of TCM injections from four key links, namely the monitoring and reporting, signal recognition, risk assessment and risk control, according to China's pharmacovigilance regulations and learning from foreign pharmacovigilance guidelines.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use].

There are many kinds and dosage forms of Chinese patent medicines for external use on the market, which are widely used in clinical departments. The common adverse reactions of Chinese patent medicines for external use are skin reactions, and those for the rare severe diseases include palpitation, chest tightness, dyspnea, and anaphylactic shock. At present, World Health Organization(WHO), International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH),the United States, the European Union, and Asia-Pacific countries(such as Japan and South Korea) have not issued any pharmacovigilance guideline of Chinese patent medicines for external use. China has not issued any pharmacovigilance guideline for these medicines, only releasing the standard Evaluation of skin adverse reactions caused by Chinese patent medicines for external use(T/CACM 005-2017). To standardize the safe and reasonable use of Chinese patent medicines for external use, Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use was developed with the joint efforts of experts in diverse disciplines. The guideline provides guidance on the monitoring and reporting of adverse reactions/events, identification and assessment of risk signals, and risk control measures in the clinical application of Chinese patent medicines for external use to guide the rational use of these medicines in clinical practice. At the same time, the possible risks and risk control measures in clinical application of Chinese patent medicines for external use are listed for clinical reference. In addition, the guideline provides guidance for risk minimization plans and the standardization of activities related to pharmacovigilance of Chinese patent medicines for external use in China.

[Pharmacovigilance guidelines of Chinese patent medicines].

Drug administration law of the People's Republic of China(2019 revised edition), which came into effect on December 1, 2019, proposed that " the state shall establish a pharmacovigilance system". Pharmacovigilance work of Chinese patent medicines is more difficult, and it is necessary to carry out Pharmacovigilance activities that are in line with the characteristics of Chinese patent medicines. Pharmacovigilance guidelines of Chinese patent medicines(T/CACM 1563. 1-2024), based on the principles of Drug Administration Law of the People's Republic of China(2019 revised edition) and Pharmacovigilance quality management standards(No. 65 of 2021) of the National Medical Products Administration, draws on the EU Pharmacovigilance regulation and the secondary guidelines of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), and it is drafted in accordance with the provisions of Guidelines for standardization work part 1: structure and drafting rules of standardization documents(GB/T1. 1-2020) based on the characteristics of Chinese patent medicines. It serves as a general document for a series of pharmacovigilance guidelines of Chinese patent medicines, such as Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions(T/CACM 1563. 2-2024), Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines(T/CACM 1563. 3-2024), Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections(T/CACM 1563. 4-2024), Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use(T/CACM 1563. 5-2024), and Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration(T/CACM 1563. 6-2024), including four major elements of pharmacovigilance monitoring and reporting of Chinese patent medicines, signal identification, risk evaluation, and risk control, as well as pharmacovigilance activities for Chinese patent medicines, ensuring the safety of public drug use.

[Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration].

The group standard Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration was released on January 16, 2024, on the national group standards information platform by the Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences and School and Hospital of Stomatology of Peking University, under the centralized management by the China Association of Chinese Medicine. The standard number is T/CACM 1563.6-2024. It aims to propose key elements and specify technical methods for safety monitoring and reporting, signal identification, risk assessment, and risk control based on the Drug administration law of the People's Republic of China(revised in 2019), which establishes normative pharmacovigilance guideline of Chinese patent medicine for mucosal administration that is in line with the characteristics of traditional Chinese Medicine(TCM) based on the pharmacovigilance content for clinical application of Chinese patent medicine for mucosal administration. The group standard has been discussed by internal and external experts through multiple rounds of consultation. It serves as a guiding document for stakeholders involved in pharmacovigilance activities, including pharmaceutical license holders, drug manufacturers, medical institutions, research institutes, and pharmaceutical trading enterprises.

Chitosan-Based Composite Aerogel with a Rapid Tissue Hydration Layer-Triggered Response to Promote Hemostasis.

Aerogels exhibit poor adhesion to wet tissue surfaces, which is a significant factor that limits their hemostatic properties. In this work, we propose a new method for investigating aerogel hemostatic materials by introducing the concept of the 'rapid tissue hydration layer-triggered property' into the hemostatic material. A chitosan derivative (Csde) with a "swollen property" was prepared via an amide reaction, followed by the incorporation of the extracted bletilla striata complex (Bscai) into the chitosan derivative to fabricate the Bscai/Csde hemostatic material. The research results indicated that the Bscai/Csde hemostatic material exhibited a rapid tissue hydration layer-triggered response, outstanding hemostasis ability, as well as excellent hemocompatibility, antibacterial properties, and cytocompatibility. Additionally, the preparation method for the Bscai/Csde hemostatic material is straightforward, and the raw materials are readily available. Therefore, this study presents a novel method for developing a hemostatic material method, and the composite aerogel hemostatic material demonstrates considerable potential for future applications.

Effect of placental mesenchymal stem cells on promoting the healing of chronic burn wounds.

The treatment of chronic burn wounds is difficult in clinical practice. The ideal therapy is required to be continuously explored. Mesenchymal stem cells revolutionize the treatment of many diseases. The placental mesenchymal stem cells (PMSCs) have the characteristics of easy access, strong proliferation ability and multi-directional differentiation potential. The aim of this study was to investigate the potential of PMSCs in chronic burn wound healing. In this study, species of bacteria of 317 patients with chronic burn wounds have been analyzed. Samples of chronic burn wound fluid were collected from representative patients and then co-cultured with cells. In vitro studies showed that chronic burn wound fluid inhibited the proliferation of human keratinocytes and fibroblasts, while PMSCs can counteract the effects of burn wound fluid on inhibiting the proliferation and migration of human keratinocytes and fibroblasts. In addition, in vivo studies showed that a rat chronic burn wound model was successfully created. The expression of MMP-2, MMP-9, MDA, IL-6 and TNF-α in chronic burn wounds was significantly higher than that in acute burn wounds. Finally, the rat chronic burn wound model was used to verify that placental mesenchymal stem cell transplantation increased the wound healing rate, decreased the wound healing time, and promoted wound healing by increasing the thickness of epidermis and promoting the expression of P63 and CK10. The findings provide support for the hypothesis that PMSCs promote the repair of chronic burn wounds and key scientific data for the application of PMSCs as a new method for treating chronic burn wounds.

Exposure to greenspaces sourced soils improves mice gut microbiota.

Greenspaces are important components of our living environment and have been linked to various human health. However, the mechanisms underlying the linkages remain unclear. Enriching microbiota has emerged as a novel mechanism, but the corresponding evidence is still limited. We collected soil samples from forest land, grassland, and barren land in Zunyi City, southwestern China and prepared soil solutions. A total of 40 BALB/c mice were evenly divided into normal control group, model control group, forest soil group, grassland soil group, and barren land soil group. After establishing the pseudo germ-free mouse model, different soil solutions were administered through gavage, lasting for seven weeks. Fecal samples were collected and a 16S rRNA high-throughput sequencing analysis was performed. Then, alpha- and beta-diversity were calculated and employed to estimate the effects of soil exposures on mice gut microbial diversity and composition. Further, Linear Discriminant Analysis Effect Size (LEfSe) analysis was carried out to evaluate the effects of soil exposures on gut microbiota specific genera abundances and functional pathways. Compared to mice exposed to barren land soils, those exposed to soils sourced from forest land showed an increase of 0.43 and 70.63 units in the Shannon index and the Observed ASVs, respectively. In addition, exposure to soils sourced from forest land and grassland resulted in healthier changes (i.e., more short-chain fatty acids (SCFAs)-producing bacteria) in gut microbiota than those from barren land. Furthermore, mice exposed to forest soil and grassland soil showed enrichment in 5 and 3 pathways (e.g., butanoate metabolism) compared to those exposed to barren land soil, respectively. In conclusion, exposure to various greenspaces soils may modify the gut microbial communities of mice, potentially fostering a more beneficial microbiota profile. Further better-designed studies are needed to validate the current findings and to explore the effects of greenspace related gut microbiota on human health.

Adverse cardiovascular and kidney outcomes in people with SARS-CoV-2 treated with SGLT2 inhibitors.

BACKGROUND: Whether use of SGLT2 inhibitors reduces the risk of cardiovascular and kidney events in people who contracted SARS-CoV-2 infection is not clear. METHODS: We used the healthcare databases of the United States Department of Veterans Affairs to build a cohort of 107,776 participants on antihyperglycemic therapy and had SARS-CoV-2 infection between March 01, 2020 and June 10, 2023. Within them, 11,588 used SGLT2 inhibitors and 96,188 used other antihyperglycemics. We examined the risks of major adverse cardiovascular events (MACE)-a composite of death, myocardial infarction and stroke, and major adverse kidney events (MAKE)-a composite of death, eGFR decline > 50%, and end stage kidney disease after balancing baseline characteristics between groups through inverse probability weighting. Survival analyses were conducted to generate hazard ratio (HR) and absolute risk reduction per 100 person-years (ARR). RESULTS: Over a median follow up of 1.57 (IQR: 1.05-2.49) years, compared to the control group, SGLT2 inhibitors use is associated with reduced risk of MACE (HR 0.82 (0.77, 0.88), ARR 1.73 (1.21, 2.25)) and reduced risk of MAKE (HR 0.75 (0.71, 0.80), ARR 2.62 (2.13, 3.11)). Compared to the control group, SGLT2 inhibitors use is associated with reduced risk of the secondary outcomes of hospitalization (HR 0.94 (0.90, 0.98), ARR 1.06 (1.36, 1.76)), anemia (HR 0.71 (0.65, 0.76), ARR 2.43 (1.95, 2.90)), and acute kidney injury (HR 0.84 (0.79, 0.89), ARR 1.86 (1.29, 2.42)). CONCLUSIONS: Among people with SARS-CoV-2 infection on antihyperglycemic therapy, compared to those on other antihyperglycemics, those on SGLT2 inhibitors have less risk of adverse cardiovascular and kidney outcomes.

SARS-CoV-2 infection leads to significant increase in risk of heart and kidney problems both shortly after infection and in the long-term. In this study, we evaluated whether SGLT2 inhibitors could reduce the risk of major adverse heart and kidney events in people with SARS-CoV-2 infection. SGLT2 inhibitors are a type of medication used to treat diabetes by lowering the amount of sugar in the blood. We compared a large group of people during and after SARS-CoV-2 infection and found that those who were using SGLT2 inhibitors had less major adverse heart and kidney problems than those who were using other types of sugar-lowering medications. Our findings could be useful for optimizing approaches to reduce risk of heart and kidney problems among people with diabetes and SARS-CoV-2 infection.

Lanthanum hydroxide@cellulose membranes with tunable pore sizes for selective removal of dyes with the same charges.

Adsorptive membranes for the efficient separation of dyes with the same charges are quite desirable. Herein, a novel membrane of lanthanum hydroxide/cellulose hydrogel coated filter paper (LC) was prepared through a facile strategy of dip-coating followed by freeze-shaping. With the aid of cellulose gel, the generated La(OH)3 achieved fine dispersion. In addition, the pore size of LC membrane could be regulated by altering the cellulose concentration or the lanthanum chloride dosage, which was crucial for its water flux. In particular, the obtained membrane possessed a high water flux (128.4 L m-2 h-1) and a high dye rejection (97.2 %) for anionic Congo red (CR) only driven by the gravity, which outperformed many previously reported membranes. More intriguingly, its dye rejection for anionic methyl orange (MO) was only 0.9 %, exhibiting high selectivity for dyes with the same charges. Single-solute adsorption experiments indicated that the CR adsorption on the membrane was best fitted by the pseudo-first-order kinetic model, and it followed the Langmuir monolayer adsorption mechanism.

Effect of combined exposure to phthalates and polycyclic aromatic hydrocarbons during early pregnancy on gestational age and neonatal size: A prospective cohort study.

Many studies have indicated that individual exposure to phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affects pregnancy outcomes. However, combined exposure to PAEs and PAHs presents a more realistic situation, and research on the combined effects of PAEs and PAHs on gestational age and newborn size is still limited. This study aimed to assess the effects of combined exposure to PAEs and PAHs on neonatal gestational age and birth size. Levels of 9 PAE and 10 PAH metabolites were measured from the urine samples of 1030 women during early pregnancy from the Zunyi Birth Cohort in China. Various statistical models, including linear regression, restricted cubic spline, Bayesian kernel machine regression, and quantile g-computation, were used to study the individual effects, dose-response relationships, and combined effects, respectively. The results of this prospective study revealed that each ten-fold increase in the concentration of monoethyl phthalate (MEP), 2-hydroxynaphthalene (2-OHNap), 2-hydroxyphenanthrene (2-OHPhe), and 1-hydroxypyrene (1-OHPyr) decreased gestational age by 1.033 days (95 % CI: -1.748, -0.319), 0.647 days (95 % CI: -1.076, -0.219), 0.845 days (95 % CI: -1.430, -0.260), and 0.888 days (95 % CI: -1.398, -0.378), respectively. Moreover, when the concentrations of MEP, 2-OHNap, 2-OHPhe, and 1-OHPyr exceeded 0.528, 0.039, 0.012, and 0.002 µg/g Cr, respectively, gestational age decreased in a dose-response manner. Upon analyzing the selected PAE and PAH metabolites as a mixture, we found that they were significantly negatively associated with gestational age, birth weight, and the ponderal index, with 1-OHPyr being the most important contributor. These findings highlight the adverse effects of single and combined exposure to PAEs and PAHs on gestational age. Therefore, future longitudinal cohort studies with larger sample sizes should be conducted across different geographic regions and ethnic groups to confirm the impact of combined exposure to PAEs and PAHs on birth outcomes.

Clinical and genetic characteristics of Chinese patients with congenital fibrosis of the extraocular muscles.

OBJECTIVE: This study aimed to describe the clinical and genetic characteristics of Chinese patients with congenital fibrosis of the extraocular muscles (CFEOM), and to evaluate the phenotype-genotype correlations in these patients. METHODS: This was a retrospective study. Patients with CFEOM underwent detailed ophthalmic examinations and magnetic resonance imaging (MRI). Panel-based next-generation sequencing was performed to identify pathogenic variants of disease-causing genes. RESULTS: Sixty-two patients with CFEOM were recruited into this study. Thirty-nine patients were diagnosed with CFEOM1 and 23 with CFEOM3. Forty-nine of the 62 patients with CFEOM carried either KIF21A (41/49) or TUBB3 variants (8/49). Six known missense variants in the KIF21A and TUBB3 genes, and a novel variant (c.3906T > A, p.D1302E) in the KIF21A gene were detected. Most patients with CFEOM1 carrying the KIF21A mutation displayed isolated CFEOM, whereas patients with CFEOM3 carrying the TUBB3 mutation had a wide range of clinical manifestations, either CFEOM alone or syndromes. Nystagmus was also present in 12 patients with CFEOM. Furthermore, the MRI findings varied, ranging from attenuation of the extraocular muscles to dysgenesis of the cranial nerves and brain structure. CONCLUSIONS: The novel variants identified in this study will further expand the spectrum of pathogenic variants in CFEOM-related genes. However, no phenotype-genotype correlations were established because of the diversity of the clinical characteristics of these patients.

Prevalence of infection and reinfection among health care workers in a hospital of Northern China between BA.5/BF.7 and XBB.1.5 wave.

BACKGROUND: To analyze the epidemiological characteristics of the SARS-CoV-2 infection and reinfection associated with the emergence of Omicron variant in Healthcare workers (HCWs). METHODS: We enrolled 760 HCWs who received 2-4 vaccination doses of COVID-19 and followed by BA.5/BF.7 and/or XBB.1.5 breakthrough infections between December 2022 and July 2023. Serum sample from each individual were collected approximately 1,3 and 6 months after last exposure. IgM, IgG and Total antibodies against SARS-CoV-2 were measured by chemiluminescent immunoassay. Meanwhile, we created an Enterprise WeChat link for HCWs to self-report SARS-CoV-2 infections, symptoms and post COVID-19 conditions. RESULTS: Our study revealed that the reinfection rate among HCWs reached 26.1%. The main symptoms were fever (91.2% vs 60.1%), cough (78.8% vs 58.0%), and sore throat (75.4% vs 59.6%) during infection and reinfection in Omicron BA.5/BF.7 and XBB.1.5 wave, and the interval for reinfection ranged from 91 to 210 days (median 152). Fatigue (23.6%), memory loss (18.8%) and coughing (18.6%) were the most prevalent long COVID symptoms, with a higher prevalence among female HCWs. CONCLUSIONS: HCWs reinfection with SARS-CoV-2 causes milder symptoms, but high reinfection rate and short intervals. Strengthen infection prevention and control is crucial to mitigating infection risk and improving health services.

Whole-Exome Sequencing and Experimental Validation Unveil the Roles of TMEM229A Q200del Mutation in Lung Adenocarcinoma.

INTRODUCTION: Lung adenocarcinoma (LUAD) is one of the major histopathological types of non-small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined. METHODS: A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole-exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the TMEM229A Q200del mutation was verified using our cohort and TCGA-LUAD datasets. The correlations between the TMEM229A Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of TMEM229A Q200del on NSCLC cell proliferation and migration were also determined. RESULTS: The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in EGFR, ATXN2, C14orf180, MUC12, NOTCH1, and PKD1L2 were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The TMEM229A Q200del mutation was only mutated in lepidic LUAD. Additionally, the TMEM229A Q200del mutation had occurred in 16 (8.8%) patients, and not found TMEM229A R76H and M346T mutations in our cohort, while TMEM229A mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA-LUAD cohort. Further correlation analysis between the TMEM229A Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of TMEM229A Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)-ERK and p-AKT (Ser473), and the reduced protein level of p-ERK in the TMEM229A Q200del group was more pronounced compared to the TMEM229A group. CONCLUSION: Our results demonstrated that the TMEM229A Q200del mutant may play a protective role in the progression of LUAD via inactivating ERK pathway, providing a potential therapeutic target in LUAD.

Immunogenicity and Safety of an Inactivated Quadrivalent Influenza Vaccine Administered Concomitantly with a 23-Valent Pneumococcal Polysaccharide Vaccine in Adults Aged 60 Years and Older.

The inactivated quadrivalent influenza vaccine (IIV4) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) have been administered for years and could be administered concomitantly if necessary. However, the immunogenicity and safety of the concomitant administration of these two vaccines have not been well documented, especially in the Chinese population. In this study, 480 participants aged 60 years and older were randomly assigned to the concomitant administration group (C group) or the separate administration group (S group) to receive IIV4 and PPSV23 either concomitantly or separately. Blood samples were collected before and 28 days after each vaccination. The antibodies against four influenza virus strains and twenty-three pneumococcus serotypes were tested. The results showed that the geometric mean titer (GMT) ratios (C group to S group) for the four influenza strains ranged from 0.72 to 0.95, with the lower limits of the 95% confidence intervals (CIs) ranging from 0.51 to 0.75, and the geometric mean concentration (GMC) ratios for the 23 pneumococcal serotypes ranged from 0.80 to 1.00, with the lower limits of 95% CIs ranging from 0.67 to 0.86. All values met the predefined criteria for non-inferiority. The incidence of adverse events was 0.63% in the C group and 1.56% in the S group. No serious adverse events were observed. In conclusion, the immunogenicity of the concomitant administration of IIV4 and PPSV23 was non-inferior to that of the separate administration, and the safety profile was favorable in adults aged 60 years and older in China.

Saikosaponin D potentiates the antineoplastic effects of doxorubicin in drug-resistant breast cancer through perturbing NQO1-mediated intracellular redox balance.

BACKGROUND: Drug resistance to doxorubicin (DOX) significantly limits its therapeutic efficacy in breast cancer (BC) patients. Saikosaponin D (SSD), a triterpene saponin derived from the traditional herb Radix Bupleuri, has shown promise as a chemotherapeutic sensitizer in preclinical studies due to its notable antitumor activity. However, the role and mechanism of SSD in DOX-resistant BC cells remain largely unexplored. PURPOSE: This study aimed to investigate the chemosensitizing effect of SSD on DOX-resistant BC and the underlying molecular mechanisms both in vitro and in vivo. METHODS: In vitro assays, including cell viability, clone formation, three-dimensional tumor spheroid growth, and apoptosis analysis, were conducted to evaluate the synergistic effect of SSD and DOX on resistant BC cells. Reactive oxygen species (ROS), GSH/GSSG, NADPH/NADP+, and NADH/NAD+ detections were employed to assess the impact of SSD on cellular redox homeostasis. Western blotting, cell cycle distribution assay, and DOX uptake assay were performed to further elucidate the possible antineoplastic mechanism of SSD. Finally, a subcutaneous MCF7/DOX cell xenografted model in nude mice was established to identify the in vivo anticarcinogenic effect of SSD combined with DOX. RESULTS: SSD significantly inhibited cell viability, proliferation, and clone formation, enhancing DOX's anticancer efficacy in vitro and in vivo. Mechanistically, SSD reduced STAT1, NQO1, and PGC-1α protein levels, leading to cellular redox imbalance, excessive ROS generation, and depletion of GSH, NADPH, and NADH. SSD induced DNA damage by disrupting redox homeostasis, resulting in G0/G1 phase cell cycle arrest. Additionally, SSD increased DOX accumulation in BC cells via inhibiting P-gp protein expression and efflux activity. CONCLUSION: We demonstrated for the first time that SSD enhances the sensitivity of chemoresistant BC cells to DOX by disrupting cellular redox homeostasis through inactivation of the STAT1/NQO1/PGC-1α signaling pathway. This study provides evidence for SSD as an adjuvant agent in drug-resistant BC treatment.

[Clinical Characteristics and Prognostic Relevance of Co-Mutated Genes in Acute Myeloid Leukemia Patients with FLT3 Mutations].

OBJECTIVE: To investigate the clinical characteristics and influence of co-mutated gene on acute myeloid leukemia patients (AML) with FMS-like tyrosine kinase-3 (FLT3) mutations. METHODS: A total of 273 FLT3+ AML patients were enrolled, and the co-mutation gene data of the patients were collected to further analyze the prognosis of the patients. FLT3 and other common mutations were quantified by PCR amplification products direct sequencing and second-generation sequencing (NGS). RESULTS: When patients were divided into FLT3- ITD +, FLT3- TKD +, FLT3- ITD ++TKD + and FLT3- ITD -+TKD - group according to the type of FLT3 mutations, it was found that the frequencies of TET2, GATA2, NRAS and ASXL1 mutation were significantly different among the 4 groups (all P < 0.05). When patients were divided into allelic ratio (AR) ≥0.5 and <0.5 group, it was found that the frequencies of FLT3- ITD +, FLT3 -ITD - +TKD -, NPM1, NRAS and C-kit were significantly different between the two groups (all P < 0.05). When patients were divided into normal and abnormal karyotype group, it was found that the frequencies of FLT3- ITD +, FLT3- TKD +, NPM1, GATA2 and C-kit were significantly different between the two groups (all P < 0.05). The median overall survival (OS) of AML patients with FLT3 -TKD + (including FLT3- ITD ++TKD +) was longer than that of patients with FLT3- ITD + alone (P < 0.05). The OS and relapse-free survival (RFS) of AML patients with FLT3++TET2+ were both shorter than those of patients with FLT3++TET2- (both P < 0.05). CONCLUSION: The mutation frequencies of co-mutated genes are correlated with subtypes of FLT3, karyotype and AR. AML patients with FLT3 -TKD + have longer OS than patients with FLT3- ITD + alone, and patients with co-mutation of TET2 have shorter median OS and RFS.

[Clinical Significance of the Levels of Peripheral Blood Tregs and Cytokines IL-35, TGF-ß and IL-10 in Hemophilia A Patients with Fâ § Inhibitor].

OBJECTIVE: To explore the levels of regulatory T cells (Tregs) and cytokines IL-35, TGF-ß and IL-10 in peripheral blood of hemophilia A(HA) patients with FⅧ inhibitor and their clinical significance. METHODS: 43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected, including 6 cases with FⅧ inhibitor and 37 cases without FⅧ inhibitor. In addition, 20 healthy males who underwent physical examinations were selected as healthy controls. Flow cytometry was used to detect the levels of CD4 + CD25 + CD127 - Tregs in peripheral blood of the HA patients and healthy controls, and ELISA assay was used to detect the expression levels of IL-35, TGF-ß and IL-10 in serum, and their differences between different groups were compared. RESULTS: Compared with the healthy control group, the level of Tregs in HA patients was decreased, and the level of Tregs in the FⅧ inhibitor positive group was the lowest, the difference was statistically significant (P <0.05). There was no significant difference in the expression level of Tregs in HA patients of different severity levels. The serum IL-35, TGF-ß, and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group, and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group (all P <0.05). CONCLUSION: The decrease of Tregs, IL-35, TGF-ß, and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.