Research progress of natural product evodiamine-based antitumor drug design strategies / 药学学报

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

The molecular mechanism of spleen-strengthening and moisture-nourishing liver prescription in treatment of acute-on-chronic liver failure based on network pharmacology and experimental verification / 中国药理学通报

To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL

Kidney-tonifying and Blood-activating Prescription Regulates Wnt/β-catenin Signaling Pathway to Improve Uterine Spiral Artery Remodeling in Mouse Model of Recurrent Miscarriage / 中国实验方剂学杂志

ObjectiveTo observe the effects of the kidney-tonifying and blood-activating prescription on the Wnt/β-catenin signaling pathway and uterine spiral artery remodeling in a mouse model of recurrent miscarriage and to explore its underlying mechanism. MethodA mouse model of normal pregnancy was established by mating CBA/J mice with BALB/c mice. A mouse model of recurrent miscarriage was established by mating CBA/J mice with DBA/2 mice. The modeled mice of recurrent miscarriage were randomized into model， dydrogesterone， and low- and high-dose Chinese medicine groups. The mice in normal pregnancy were used as the control group. Each group consisted of 10 mice， and the drug administration lasted for 14 days. After the treatment， the embryo absorption rate of each group was recorded. Hematoxylin-eosin （HE） staining was employed to observe the pathological morphology of the uterine decidua， and the physiological transformation rate of spiral arteries （SPA） was evaluated. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to determine the mRNA and protein levels， respectively， of matrix metalloproteinases （MMP）-2， MMP-9， vascular endothelial growth factor （VEGF）， and Wnt/β-catenin signaling pathway. ResultCompared with the control group， the model group presented increased embryo absorption rate （P<0.05）， decreased physiological transformation rate of uterine SPA （P<0.05）， cellular swelling， degeneration， and disordered arrangement in the uterine decidua tissue， and down-regulated mRNA and protein levels of key factors involved in SPA remodeling （MMP-2， MMP-9， VEGF） and the Wnt/β-catenin signaling pathway （Wnt2， β-catenin， Cyclin D1， c-Myc） （P<0.05）. Compared with the model group， both the low- and high-dose Chinese medicine reduced embryo absorption rate （P<0.05）， increased SPA physiological transformation rate （P<0.05）， improved uterine decidua tissue morphology， and increased decidua vessel count. Furthermore， they up-regulated the mRNA and protein levels of MMP-2， MMP-9， VEGF， and proteins in the Wnt/β-catenin signaling pathway （P<0.05）. ConclusionRecurrent miscarriage is associated with impaired uterine spiral artery remodeling. The kidney-tonifying and blood-activating prescription can promote uterine spiral artery remodeling by activating the Wnt/β-catenin signaling pathway and promoting the expression of VEGF， MMP-2， and MMP-9， thus treating recurrent miscarriage.

Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images / 中国结合医学杂志

OBJECTIVE@#To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images.@*METHODS@#Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.@*RESULTS@#A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set.@*CONCLUSIONS@#The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.

Spatial and temporal expression patterns of Atoh1 during mice cerebellar development / 解剖学报

Objective To investigated the spatial and temporal expression of Atoh1 mRNA and protein level during the cerebellar development. Methods The frozen cerebellum sections of mice at different developmental stages were used to analyze the temporal and spatial expression patterns of Atoh1 mRNA by RNA scope technique, n= 3 for each group. Meanwhile, two reporter mice with different genetic modification method were utilized to analyze the spatial and temporal expression of Atoh1 at the protein level by immunofluorescence staining, n= 3 for each group. Results Atoh1 mRNA was highly expressed in the embryonic cerebellar rhombic lip (RL) and the external granule layer (EGL). At the protein level, staining result of Atoh1-3

Intervention of physcion-8-O-β-D-monoglucoside on acute liver injury induced by CCl 4 in mice by regulating PI3K/AKT/NF-κB / 中国药理学通报

Aim To investigate the effect of PI3K/AKT/NF-κB signaling pathway in the treatment of physicion-8-O-β-D-monoglu-coside(PMG) on acute liver injury induced by carbon tetracloride(CCl 4) in mice . Methods Mice were randomly assigned into control group, model group, PMG low-dose, medium-dose and high-dose groups and Bifendate groups. After the continuous intervention with PMG for three days, CCl 4oil solution was intraperitoneally injected to establish acute liver injury mouse models, and samples were collected sixteen hours later. HE staining was used to observe the pathological changes of liver tissue. Hoechst 33342 staining was used to detect the number of apoptotic hepatocytes. Western blot was employed to detect the expression levels of caspase-3, PI3K, p-PI3K, AKT, p-Akt, IκB, p-IκB total protein and the nuclear protein NF-κB p65 in mouse liver tissue. The proportion of Th17 cells in mouse liver tissue was detected by FACS. Results After three days of PMG treatment, the pathological injury of liver tissue was relieved, the apoptosis of liver cells and the protein levels of caspase-3(P<0.01) were induced compared with model group.PMG could significantly decrease the nuclear expression of NF-κB p65 in the liver of mice with acute liver injury(P<0.05 or P<0.01). The phosphorylation levels of PI3K, AKT and IκB significantly decreased by PMG(P<0.05 or P <0.01). Otherwise, the proportion of Th17 cells in liver tissue was significantly reduced after PMG treatment(P<0.01). Conclusion PMG can alleviate CCl4 - induced acute liver injury through PI3K/AKT/NF-κB signaling pathway.

The molecular mechanism of Qizhu anti-cancer prescription in treatment of primary liver cancer based on network pharmacology and experimental verification / 中国药理学通报

Aim To investigate the mechanism of Qizhu anti-cancer prescription ( QZACP) inthe treatment of primary liver cancer using network pharmacology and molecular docking. Methods Drugs and primary liver cancer ( PLC) -related targets were found according to TCMSP database and disease databases such as GeneCard, the key chemical components and core targets were screened by Cytoscape 3. 9. 1 and String platform respectively, and a network relationship diagram of traditional Chinese medicine-active component-target was constructed by using Cytoscape 3.9. 1. GO functional analysis and KEGG pathway analysis were performed using DAVID platform, visualized by R 4. 1. 1 software, and finally the core clustered proteins were analyzed by CytoNCA plug-in to obtain the core action targets, and the core components and key targets were verified by using molecular docking technology and the pharmacodynamic mechanism of QZACP was further verified by animal experiments. Results The active ingredients of QZACP in the treatment of primary liver cancer may be quercetin, glycyrrhizin, Denudatin B, isoflavanone, sanguinarol, etc. ; the potential targets were STAT3, EGFR, AKT1 etc. ; the related pathways were mainly PI3K-Akt signaling pathway,MAPK signaling pathway,etc. ; molecular docking showed that the core compounds had better integrating conformation with the key targets. In addition, QZACP could inhibit the growth of tumor in nude mice and decrease the expression of STAT3, EGFR and AKT1. Conclusions Qizhu anti-cancer prescription may have some positive significance in the treatment of primary liver cancer, which may be related to the regulation of PI3K/Akt signaling pathway.

Study of dental arch width in patients with idiopathic condylar resorption / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the relationship between idiopathic condylar resorption （ICR） and arch width disorder. Methods:Thirty-two patients with ICR and twenty patients without condylar resorption were enrolled according to the same inclusion criteria. They were divided into experimental group and control group. The experimental group was divided into unilateral ICR group and bilateral ICR group according to the affected side of condylar resorption, and then experimental group was divided into subgroups ICR Ⅰ, ICRⅡand ICR Ⅲ according to the degree of condylar resorption. Patients with no condylar resorption were used as a control group. The width of anterior, middle and posterior segments of dental arch on cone beam computed tomography（CBCT） was measured and the two groups of measured values were statistically analyzed. Results:Compared with the control group, the width of maxillary anterior, middle and posterior segments in ICR group was significantly reduced, and the difference was statistically significant（P<0.01）. But the width of mandibular segment was not significantly different from that in control group（P>0.05）. There was no significant difference in the width of anterior, middle and posterior dental arch between subgroups（P>0.05）. Conclusion:Almost all patients with ICR have malocclusion of maxillary and mandibular arch width, but there is no significant correlation between the malocclusion width and the severity of condylar resorption.

Analyzing the evolution of insect TMED gene and the expression pattern of silkworm TMED gene / 生物工程学报

Transmembrane emp24 domain (TMED) gene is closely related to immune response, signal transduction, growth and disease development in mammals. However, only the Drosophila TMED gene has been reported on insects. We identified the TMED family genes of silkworm, Tribolium castaneum, tobacco moth and Italian bee from their genomes, and found that the TMED family gene composition patterns of one α-class, one β-class, one δ-class and several γ-classes arose in the common ancestor of pre-divergent Hymenoptera insects, while the composition of Drosophila TMED family members has evolved in a unique pattern. Insect TMED family γ-class genes have evolved rapidly, diverging into three separate subclasses, TMED6-like, TMED5-like and TMED3-like. The TMED5-like gene was lost in Hymenoptera, duplicated in the ancestors of Lepidoptera and duplicated in Drosophila. Insect TMED protein not only has typical structural characteristics of TMED, but also has obvious signal peptide. There are seven TMED genes in silkworm, distributed in six chromosomes. One of seven is single exon and others are multi-exons. The complete open reading frame (ORF) sequences of seven TMED genes of silkworm were cloned from larval tissues and registered in GenBank database. BmTMED1, BmTMED2 and BmTMED6 were expressed in all stages and tissues of the silkworm, and all genes were expressed in the 4th and 5th instar and silk gland of the silkworm. The present study revealed the composition pattern of TMED family members, their γ class differentiation and their evolutionary history, providing a basis for further studies on TMED genes in silkworm and other insects.

Curative effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum β-EP level in puerpera / 中国针灸

OBJECTIVES@#To observe the clinical effect of wrist-ankle acupuncture on postpartum abdominal pain and its influence on serum beta-endorphin (β-EP) level in puerpera.@*METHODS@#Seventy patients with postpartum abdominal pain were randomly divided into an acupuncture + herbal medication group (35 cases, 1 case dropped out) and a herbal medication group (35 cases, 2 cases dropped out). In the herbal medication group, 1 day after delivery, modified shenghua decoction was taken orally, one dose a day. In the acupuncture + herbal medication group, on the basis of herbal medication, wrist-ankle acupuncture was given at the Lower 1 and Lower 2 of the ankles, once daily. The duration of treatment was 3 days in the two groups. Before and after treatment, the score of visual analogue scale (VAS) for pain, serum β-EP level, uterine fundus height, postpartum conditions of lochia and the uterine recovery at 42 days postpartum were compared in the patients of the two groups.@*RESULTS@#At each time point after treatment (24 h, 48 h and 72 h after delivery), VAS scores and the uterine fundus height were reduced as compared with those before treatment (2 h after delivery) in the two groups (P<0.05); these indexes in the acupuncture + herbal medication group were lower than those in the herbal medication group (P<0.05). After treatment (72 h after delivery), β-EP levels in the serum were increased when compared with those before treatment in the two groups (P<0.05), and the β-EP level in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05). The volume of postpartum lochia discharge in the acupuncture + herbal medication group was higher than that in the herbal medication group (P<0.05), while the duration of postpartum lochia discharge and the total time of lochia discharge were shorter (P<0.05). Regarding the recovery of the uterus at 42 days postpartum, there was no statistical significance between the two groups (P>0.05).@*CONCLUSIONS@#Wrist-ankle acupuncture obviously reduces the degree of postpartum abdominal pain and promotes the lochia discharge and the uterine recovery. The effect mechanism may be related to the up-regulation of serum β-EP level and the increase of pain threshold so that analgesia is obtained.

Effect of Human Bone Marrow Mesenchymal Stem Cells with Ectopic High OCT4 Expression on T Lymphocyte Function / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of human bone marrow mesenchymal stem cells (MSCs) with ectopic high OCT4 expression on T-cell proliferation, activation and secretion in vitro.@*METHODS@#Peripheral blood mononuclear cells were isolated from healthy children. Anti-CD3 and anti-CD28 monoclonal antibodies were used to activate T lymphocytes, which were stimulated by interleukin (IL)-2 for one week in vitro. Then MSCs with ectopic high OCT4 expression (MSC-OCT4) were co-cultured with activated T lymphocytes. After one week of co-culture, the supernatant was collected and the levels of Th1/Th2 cytokines [IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ] were determined by flow cytometry. The lymphocytes after one week of co-culture were collected and counted by Countstar software. After the proportions of activated/inactivated T cell subsets were determined by flow cytometry, the absolute lymphocyte counts were calculated and expressed as mean ± standard deviation.@*RESULTS@#Compared with control T cell alone culture group, the proliferation of CD3+ T cells, CD3+CD4+ T cells, and CD3+CD8+ T cells were significantly inhibited in MSC group and MSC-OCT4 group. Compared with MSC, MSC-OCT4 could inhibit CD3+CD8+ T cell proliferation better (P =0.049), and mainly inhibited early T cell activation. Compared with control T cell alone culture group, the levels of IL-2 and INF-γ were significantly down-regulated both in MSC group and MSC-OCT4 group.After co-culture with T cells for one week, the level of IL-6 significantly increased in MSC group and MSC-OCT4 group compared with that before co-culture. Compared with control MSC group, MSC-OCT4 group had higher viable cell numbers after 1 week of co-culture (P =0.019), and could resist the inhibition of proliferation by higher concentration of mitomycin C.@*CONCLUSION@#Both MSC and MSC-OCT4 can inhibit the proliferation and activation of IL-2-stimulated T cells in vitro. After overexpression of OCT4, MSC has better proliferation ability in vitro and can inhibit the proliferation of CD3+CD8+ T cells more effectively, which may have a better and more lasting immunosuppressive ability to regulate the balance of Th1/Th2.

Preliminary observation on the clinical application of rehabilitation support for lumbar disc herniation based on 3D printing technology / 中国骨伤

OBJECTIVE@#To analyze the important effect of 3D printing personalized lumbar support on lumbar pain and lumbar function in patients with lumbar disc herniation.@*METHODS@#From October 2018 to May 2021, 60 patients initially diagnosed with lumbar disc herniation were selected and divided into an observation group and a control group, with 30 patients in each group. Among them, there were 18 males and 12 females in the observation group;the age ranged from 24 to 56 years old, with an average of (45.23±6.07) years old. The course of disease ranged from 1 to 24 months, with an average of(6.25±0.82) months, and rehabilitation treatment was carried out by wearing 3D printed personalized lumbar support. There were 19 males and 11 females in the control group;the age ranged from 25 to 57 years old, with an average of (42.78±7.58) years old. The course of disease ranged from 1 to 24 months, with an average of (6.72±1.36) months, and rehabilitation treatment is carried out by wearing traditional lumbar protective equipment. The Japanese Orthopaedic Association (JOA) scores, lumbar Oswestry dysfunction index (ODI) and visual analogue scale (VAS) were evaluated and compared between the two groups before and 1 course after treatment (3 weeks).@*RESULTS@#There was no statistically significant difference in JOA, ODI, and VAS between two groups before treatment (P>0.05). After one course of treatment (3 weeks), JOA scores of both groups was increased compared to before treatment (P<0.05), while ODI and VAS decreased compared to before treatment (P<0.05). After treatment, JOA score of observation group was higher than that of control group (P<0.05), while ODI and VAS scores were lower than those of control group. No adverse events occurred in both groups.@*CONCLUSION@#The application of 3D printing personalized lumbar support can effectively alleviate the pain of patients with lumbar disc herniation and improve their lumbar function of patients.

An improved 4-vessel intermittent occlusion method for establishing rat models of global cerebral ischemia-reperfusion injury / 南方医科大学学报

OBJECTIVE@#To improve the classical 4-vessel occlusion (4VO) model established by Pulsinelli and Brierley.@*METHODS@#Thirty-two male SD rats were randomized into sham operation group, I4VO-Con10 group, I4VO-Int10 group and I4VO-Int15 group. The sham surgery group underwent exposure of the bilateral vertebral arteries and carotid arteries without occlusion to block blood flow. The I4VO-Con10 group experienced continuous ischemia by occluding the bilateral vertebral arteries and carotid arteries for 10 minutes followed by reperfusion for 24 hours. The I4VO-Int10 and I4VO-Int15 groups were subjected to intermittent ischemia. The I4VO- Int10 group underwent 5 minutes of ischemia, followed by 5 minutes of reperfusion and another 5 minutes of ischemia, and then reperfusion for 24 hours. The I4VO-Int15 group experienced 5 minutes of ischemia followed by two cycles of 5 minutes of reperfusion and 5 minutes of ischemia, and then reperfusion for 24 hours. The regional cerebral blood flow (rCBF) was monitored with laser Doppler scanning, and survival of the rats was observed. HE staining was used to observe hippocampal pathologies to determine the optimal method for modeling. Another 48 rats were randomized into 6 groups, including a sham operation group and 5 model groups established using the optimal method. The 5 I4VO model groups were further divided based on the reperfusion time points (1, 3, 7, 14, and 28 days) into I4VO-D1, I4VO-D3, I4VO-D7, I4VO- D14, and I4VO- D28 groups. Body weight changes and survival of the rats were recorded. HE staining was used to observe morphological changes in the hippocampal, retinal and optic tract tissues. The Y-maze test and light/dark box test were used to evaluate cognitive and visual functions of the rats in I4VO-D28 group.@*RESULTS@#Occlusion for 5 min for 3 times at the interval of 5 min was the optimal method for 4VO modeling. In the latter 48 rats, the body weight was significantly lower than that of the sham-operated rats at 1, 3, 7, 14 and 28 days after modeling without significant difference in survival rate among the groups. The rats with intermittent vessel occlusion exhibited progressive deterioration of hippocampal neuronal injury and neuronal loss. Cognitive impairment was observed in the rats in I4VO-D28 group, but no obvious ischemic injury of the retina or the optic tract was detected.@*CONCLUSION@#The improved 4VO model can successfully mimic the main pathological processes of global cerebral ischemia-reperfusion injury without causing visual impairment in rats.

Progress based on the clinical translation of the anxiolytic effects of oxytocin / 四川精神卫生

The etiology and pathogenesis of anxiety disorders were still unknown with limited progress in treatment， and had a low cure rate and a high relapse rate. Oxytocin has attracted attention in recent years due to its anxiolytic effect， especially validated in animal experiments， but there are few studies in humans. Therefore， the purpose of this paper is to illustrate the pathological mechanism of anxiety through review researches on oxytocin and anxiety in recent years. Anxiety disorder is one of the most common mental disorder， and the imbalance of neurotransmitters is one of the pathogenesis. As a common neurotransmitter in the brain， oxytocin participated in the process of anxiety regulation. The purpose of this article is to summarize the research related to oxytocin to explore its possible mechanism of regulating anxiety， and to provide new ideas for diagnosis and treatment of anxiety disorders in combination with the clinical findings. ［Funded by Zhejiang Health Science and Technology Plan （number， 2022KY367）］.

Summary of experience with patterning cropped and shaped mesh repair for perineal hernia after abdominoperineal excision in rectal cancer / 中华外科杂志

Objective: To examine the patterning cropped and shaped mesh repair for perineal hernia after abdominoperineal excision (APE) in rectal cancer. Methods: The clinical data of 8 patients with perineal hernia after APE who accepted surgical treatment in the Department of Hepatopancreatobiliary and Hernia Surgery, the First Affiliated Hospital of Fujian Medical University from March 2017 to December 2022 were retrospectively reviewed. There were 3 males and 5 females, aged (67.6±7.2) years (range: 56 to 76 years). Eight patients developed a perineal mass at (11.3±2.9) months (range: 5 to 13 months) after APE. After surgical separation of adhesion and exposing the pelvic floor defect, a 15 cm×20 cm anti-adhesion mesh was fashioned as a three-dimensional pocket shape to fit the pelvic defect, then fixed to the promontory or sacrum and sutured to the pelvic sidewalls and the anterior peritoneum, while two side slender slings were tailored in front of the mesh and fixed on the pectineal ligament. Results: The repair of their perineal hernias went well, with an operating time of (240.6±48.8) minutes (range: 155 to 300 minutes). Five patients underwent laparotomy, 3 patients tried laparoscopic surgery first and then transferred to laparotomy combined with the perineal approach. Intraoperative bowel injury was observed in 3 patients. All patients did not have an intestinal fistula, bleeding occurred. No reoperation was performed and their preoperative symptoms improved significantly. The postoperative hospital stay was (13.5±2.9) days (range: 7 to 17 days) and two patients had postoperative ileus, which improved after conservative treatment. Two patients had a postoperative perineal hernia sac effusion, one of them underwent placement of a tube to puncture the hernia sac effusion due to infection, and continued irrigation and drainage. The postoperative follow-up was (34.8±14.0) months (range: 13 to 48 months), and 1 patient developed recurrence in the seventh postoperative month, no further surgery was performed. Conclusions: Surgical repair of the perineal hernia after APE can be preferred transabdominal approach, routine application of laparoscopy is not recommended, combined abdominoperineal approach can be considered if necessary. The perineal hernia after APE can be repaired safely and effectively using the described technique of patterning cropped and shaped mesh repair.

Immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine in people aged 60 years and above / 中华流行病学杂志

Objective: To evaluate the immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine (PPV23) in elderly people aged ≥60 years. Methods: The elderly aged ≥60 years with 1 dose of PPV23 vaccination were selected as revaccination group and those without history of pneumococcal vaccine immunization were selected as the first vaccination group. One dose of PPV23 was administered to both groups, and the first blood samples were collected before vaccination while the second blood samples were collected on day 28-40 after vaccination. ELISA was used to detect the concentrations of anti-specific serotype Streptococcus pneumoniae podocyte polysaccharide immunoglobulin G, and the safety of the vaccination was evaluated after 30 days. Results: The geometric mean concentration (GMC) of antibody to 23 serotypes before the vaccination (0.73-13.73 μg/ml) was higher in revaccination group than in the first vaccination group (0.39-7.53 μg/ml), the GMC after the vaccination (1.42-31.65 μg/ml) was higher than that before the vaccination (0.73-13.73 μg/ml) in the revaccination group, and the GMC after the vaccination (1.62-43.76 μg/ml) was higher than that before the vaccination (0.39-7.53 μg/ml) in the first vaccination group; the geometric mean growth multiple in revaccination group (2.16-3.60) was lower than that in the first vaccination group (3.86-16.13); The mean 2-fold antibody growth rate was lower in revaccination group (53.68%, 95%CI: 52.30%-55.06%) than in the first vaccination group (93.16%, 95%CI: 92.18%- 94.15%), all differences were significant (P<0.001). After the vaccination, 13 serotypes of GMC were higher in the first vaccination group than in revaccination group (P<0.001), the differences were not significant for 10 serotypes of GMC (P>0.05). The incidence of local adverse reaction was 19.20% and 13.27% in revaccination group and the first vaccination group, respectively (P=0.174). Conclusions: The antibody level in ≥60 years people who received one dose of PPV23 after a 5-year interval was still higher than that in unvaccinated people. The antibody level decreased after 5 years of the first vaccination, and the antibody level could be rapidly increased by one more dose vaccination, but the overall immune response was lower than that of the first vaccination; revaccination with PPV23 has a good safety.

Establishment of a recombined mannose-binding lectin protein-magnetic beads-enriched binding recombinant enzyme-assisted polymerase chain reaction assay for Candida in blood samples / 中华流行病学杂志

Objective: To establish a nested recombinant enzyme-assisted polymerase chain reaction (RAP) technique combined with recombined mannose-binding lectin protein (M1 protein)-magnetic beads enrichment for the detection of Candida albicans (C. albicans) and Candida tropicalis (C. tropicalis) in blood samples for the early diagnosis of candidemia albicans and candidiemia tropicalis. Methods: The primer probes for highly conserved regions of the internal transcribed spacerregions of C. albicans and C. tropicalis were deigned to establish RAP assays for the detections of C. albicans and C. tropicalis; The sensitivity and reproducibility of nucleic acid tests with gradient dilutions of standard strains and specificity of nucleic acid tests with common clinical pathogens causing bloodstream infection were condcuted. M1 protein-magnetic bead enriched plasma C. albicans and C. tropicalis were used for RAP and PCR in with simulated samples and the results were compared. Results: The sensitivity of the established dual RAP assay was 2.4-2.8 copies/reaction, with higher reproducibility and specificity. M1 protein-magnetic bead enrichment of pathogen combined with the dual RAP assay could complete the detections of C. albicans and C. tropicalis in plasma within 4 hours. Fie the pathogen samples at concentration <10 CFU/ml, the number of the samples tested by RAP was higher than that tested by PCR after enrichment. Conclusion: In this study, a dual RAP assay for the detections of C. albicans and C. tropicalis in blood sample was developed, which has the advantages of accuracy, rapidity, and less contaminants and has great potential for rapid detection of Candidemia.

Effect of health management service for hypertension patients under framework of Basic Public Health Service Project: a regression discontinuity design / 中华流行病学杂志

Objective: To evaluate the effect of health management service on hypertension patients (HMSFHP) under the framework of the Basic Public Health Service Project by using regression discontinuity design. Methods: The participants were enrolled from an observational cohort survey in 2015 and followed up was conducted in 2019. The participants with SBP 130-150 mmHg and/or DBP 80-100 mmHg in the baseline survey of the cohort in 2015 were included in the present study. Additionally, we obtained the dates of participants receiving HMSFHP and their blood pressure data from follow-up records, physical examination records and telephone interview. The participants were divided into intervention group and control group based on the cutoff points, i.e. SBP ≥140 mmHg and/or DBP ≥90 mmHg. The local linear regression model were used to estimate the effect of HMSFHP on reducing blood pressure of the participants. Results: After adjusting for age, sex and time length of receiving HMSFHP, the results of the model including participants with 80-100 mmHg for DBP in 2015 indicated that, for the participants who received HMSFHP, the DBP decreased by 6.66 mmHg from 2015 to 2019. For the participants with SBP 130-150 mmHg in 2015, the reduction estimate of the model was -6.17 mmHg, the difference was not significant (P=0.178), suggesting that receiving HMSFHP did not cause change in SBP for the participants who received HMSFHP. Conclusion: Receiving HMSFHP had effect to reduce DBP, and HMSFHP had a positive effect on the control of blood pressure in patients with hypertension.

Enlightening from optimizing post-authorization safety monitoring system of SARS-CoV-2 vaccines in major economies worldwide / 中华预防医学杂志

Ongoing global pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has promoted the unprecedented rapid development and large-scale rolling out of different platform-based COVID-19 vaccines worldwide. How to effectively respond to the expected scale increasing adverse events after vaccination campaign of COVID-19 vaccines is a common problem faced by the world. A lot of countries and regions around the world have arranged in advance at different levels, optimizing the original vaccine safety monitoring system from the perspectives of strengthening the foundation and capabilities, promoting internal and external cooperation, upgrading methods, as well as improving transparency and public communication, which has ensured the good and efficient operation of the system and can provide reference for the construction of relevant fields in China.

Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge

Background@#Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. @*Methods@#We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. @*Results@#In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing.Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. @*Conclusion@#This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.