Hydroxysafflor Yellow A Promotes HaCaT Cell Proliferation and Migration by Regulating HBEGF/EGFR and PI3K/AKT Pathways and Circ_0084443 / 中国结合医学杂志

OBJECTIVE@#To investigate the effect and possible mechanism of hydroxysafflor yellow A (HSYA) on human immortalized keratinocyte cell proliferation and migration.@*METHODS@#HaCaT cells were treated with HSYA. Cell proliferation was detected by the cell counting kit-8 assay, and cell migration was measured using wound healing assay and Transwell migration assay. The mRNA and protein expression levels of heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF), EGF receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF-1α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Circ_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with HSYA. The expression of circ_0084443 was detected by qRT-PCR.@*RESULTS@#HSYA (800 µmol/L) significantly promoted HaCaT cell proliferation and migration (P<0.05 or P<0.01). It also increased the mRNA and protein expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and increased the phosphorylation levels of PI3K and AKT (P<0.05 or P<0.01). Furthermore, HSYA promoted HaCaT cell proliferation and migration via the HBEGF/EGFR and PI3K/AKT/mTOR signaling pathways (P<0.01). Circ_0084443 attenuated the mRNA expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α (P<0.05). HSYA inhibited the circ_0084443 expression, further antagonized the inhibition of circ_0084443 on HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and promoted the proliferation of circ_0084443-overexpressing HaCaT cells (P<0.05 or P<0.01). However, HSYA could not influence the inhibitory effect of circ_0084443 on HaCaT cell migration (P>0.05).@*CONCLUSION@#HSYA played an accelerative role in HaCaT cell proliferation and migration, which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways, and had a particular inhibitory effect on the keratinocyte negative regulator circ_0084443.

Study on fluvoxamine maleate sustained-release pellets and its compression technology / 药学学报

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (24) Taguchi experiment. Using Minitab software to design a DOE experiment with 24 partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

Effect of radix scutellariae microemulsion gel on chronic eczema in mice model / 中国临床药理学与治疗学

AIM: To prepare radix scutellariae microemulsion gel and investigate its therapeutic effect on chronic eczema based on the previous research of radix scutellariae self microemulsion. METHODS: The gel matrix and humectant were optimized by single factor method and response surface method to obtain the formula and preparation technique of the gel. The Franz diffusion cell method was used to evaluate the transdermal properties of microemulsion and microemulsion gel in vitro. By establishing a chronic eczema model in the mouse ear, the swelling degree, swelling inhibition rate, pathological changes and tumor necrosis factor α (TNF-α), Interleukin-1β (IL-1β) and interleukin - 6 (IL-6) of radix scutellariae microemulsion gel were measured, to investigate the therapeutic effect on chronic eczema in mice. RESULTS: The physical and chemical properties of radix scutellariae microemulsion gel were stable. Compared with microemulsion, the microemulsion gel had better transdermal performance. The cumulative transdermal amount of baicalein and wogonin, the main components of microemulsion gel, was 1.85 times and 2.77 times of that of microemulsion respectively. Moreover, the steady flow rate and permeability coefficient of microemulsion gel significantly increased, and the lag time significantly shortened. Pharmacodynamic study showed that compared with the model group, the radix scutellariae microemulsion gel could significantly reduce the ear swelling of mice (P<0.05), and the serum inflammatory factor TNF - α, IL-1β and IL-6 reduced content by over 37%. Compared with the radix scutellaria aqueous extract and aqueous extract gel, the treatment of chronic eczema was better. CONCLUSION: The preparation process of radix scutellaria microemulsion gel is feasible, with strong transdermal property, and a significant therapeutic effect on chronic eczema.

Surveillance of echinococcosis in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022 / 中国血吸虫病防治杂志

Objective To analyze the echinococcosis surveillance results in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022, so as to provide insights into formulation of echinococcosis control measures in the prefecture. Methods Villagers were randomly sampled using a multistage sampling method from class I and II echinococcosis endemic counties in Bayingolin Mongolian Autonomous Prefecture from 2017 to 2022 for detection of human echinococcosis, while all patients undergoing ultrasound examinations in medical institutions in class III endemic counties received active echinococcosis screening. In addition, livestock in centralized slaughterhouses or slaughtering sites were screened for echinococcosis using the palpation and necropsy method, and fresh domestic dog feces samples were collected from randomly selected dog owners in each administrative village for detection of Echinococcus copro-antigen in domestic dogs. The trends in detection of human and livestock echinococcosis, detection of newly diagnosed human echinococcosis cases and detection of Echinococcus coproantigen in domestic dogs were analyzed in Bayingolin Mongol Autonomous Prefecture from 2017 to 2022. Results The mean detection rate of human echinococcosis was 0.13% (540/407 803) in Bayingolin Mongol Autonomous Prefecture from 2017 to 2022, which appeared a tendency towards a decline over years (χ2trend = 1 217.21, P < 0.001), and the highest detection of newly diagnosed echinococcosis cases was seen in Hejing County (0.28%, 191/67 865). The detection of livestock echinococcosis appeared a tendency towards a decline over years from 2017 to 2022 (χ2trend = 147.02, P < 0.001), with the highest detection rate seen in Hejing County (3.44%, 86/2 500), and the detection of Echinococcus copro-antigen in domestic dogs appeared a tendency towards a decline over years from 2017 to 2022 (χ2trend = 302.46, P < 0.001), with the highest detection rate in Qiemo County (2.74%, 118/4 313). Conclusions The detection of human and livestock echinococcosis and dog feces antigens Echinococcus copro-antigen in domestic dogs all appeared a tendency towards a decline in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022; however, there is still a high echinococcosis transmission risk in local areas. Sustainable integrated echinococcosis control is required in Bayingolin Mongol Autonomous Prefecture.

Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumors: a report of 15 cases in a national medical center / 中华妇产科杂志

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.

Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Surveillance results of diarrhea in Minhang District of Shanghai City in 2018-2020 / 公共卫生与预防医学

Objective To investigate the epidemic features and pathogen spectrum distribution of diarrhea cases in Minhang District of Shanghai City so as to provide scientific evidence for developing prevention and control measures. Methods Surveillance on diarrhea was conducted in sentinel hospitals in Minghang District from 2018 to 2020. According to the quantity of outpatients in the monitoring hospital, the stool samples were collected by systematic sampling method according to the fixed interval proportion in the case queue which met the requirements of the monitored cases, and the pathogenic composition and epidemiological characteristics were analyzed. Results Among the 721 samples detected , 307(42.58%) were pathogen positive, The main positive bacteria was Vibrio parahaemolyticus, which accounted for 36.11%(39/108) among all positive bacteria.The main positive virus was norovirus GII, which accounted for 24.43%(75/307) among all positive virus. Positive cases were detected among all age groups. 81 positive cases (26.38%) were detected among 31-40 years old, with the highest detection rate. There was no difference in the positive detection rate between genders(χ2= 1.95, P = 0.16). The positive cases showed two peaks during the season of winter and spring. The positive rate of bacteria was highest in the third quarter and positive rate of viruses was highest in the first quarter. The mixed infection rate of bacteria and viruses was highest in the second quarter. Conclusions Diarrhea cases in Minhang District of Shanghai from 2018 to 2020 is caused by a variety of pathogens and related seasonality is obvious in Minghang District, Shanghai City in 2018-2020. It is necessary to take specific prevention based on various pathogens to reduce the incidence of diarrhea.

Mediating effect of self-efficacy on self-management ability and self-management behavior in patients with type 2 diabetes mellitus / 北京大学学报(医学版)

OBJECTIVE@#To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests.@*METHODS@#In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years.@*RESULTS@#In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect.@*CONCLUSION@#Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.

Research progress of FAPI PET/CT in the diagnosis of malignant liver tumors / 中华肝脏病杂志

Malignant liver tumors have a high incidence and mortality rate. Therefore, it is of great significance to promptly learn about tumor advancement status through relevant examinations for patients' follow-up, diagnosis, and therapy as well as the improvement of the five-year survival rate. The primary lesions and intrahepatic metastases of malignant liver tumors have been better demonstrated in the clinical study with the use of various isotope-labeled fibroblast activating protein inhibitors because of their low uptake in liver tissues and high tumor/background ratio, which provides a new method for early diagnosis, precise staging, and radionuclide therapy. In light of this context, a review of the research progress of fibroblast-activating protein inhibitors for the diagnosis of liver malignant tumors is presented.

Analysis of the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022 / 中华预防医学杂志

Objective: To explore the characteristics of viral infections in children with diarrhea in Beijing from 2018 to 2022. Methods: Real-time PCR and enzyme-linked immunosorbent assay were used to detect viral nucleic acid of Norovirus (NoV), Sappovirus (SaV), Astrovirus (AstV), Enteric Adenovirus (AdV) or antigen of Rotavirus (RV) in 748 stool samples collected from Beijing Capital Institute of Pediatrics from January 2018 to December 2021. Subsequently, the reverse transcription PCR or PCR method was used to amplify the target gene of the positive samples after the initial screening, followed by sequencing, genotyping and evolution analysis, so as to obtain the characteristics of these viruses. Phylogenetic analysis was performed using Mega 6.0. Results: From 2018 to 2021, the overall detection rate of the above five common viruses was 37.6%(281/748)in children under 5 years old in Beijing. NoV, Enteric AdV and RV were still the top three diarrhea-related viruses, followed by AstV and SaV, accounting for 41.6%, 29.2%, 27.8%, 8.9% and 7.5%, respectively. The detection rate of co-infections with two or three diarrhea-related viruses was 4.7% (35/748). From the perspective of annual distribution, the detection rate of Enteric AdV was the highest in 2021, while NoV was predominant in the other 4 years. From the perspective of genetic characteristics, NoV was predominant by GⅡ.4, and after the first detection of GⅡ.4[P16] in 2020, it occupied the first two gene groups together with GⅡ.4[P31]. Although the predominant RV was G9P[8], the rare epidemic strain G8P[8] was first detected in 2021. The predominant genotypes of Enteric AdV and AstV were Ad41 and HAstV-1. SaV was sporadic spread with a low detection rate. Conclusion: Among the diarrhea-related viruses infected children under 5 years of age in Beijing, the predominant strains of NoV and RV have changed and new sub-genotypes have been detected for the first time, while the predominant strains of AstV and Enteric AdV are relatively stable.

Association between coagulation function indicators and placental abruption among preeclampsia-eclampsia pregnant women / 中华预防医学杂志

Objective: To explore the association between coagulation function indicators and placental abruption (PA) in different trimesters of pregnancy among preeclampsia-eclampsia pregnant women. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study and were diagnosed with preeclampsia, eclampsia and chronic hypertension with superimposed preeclampsia in Beijing Obstetrics and Gynecology Hospital were enrolled in this study. The baseline and follow-up information were collected by questionnaire survey, and the coagulation function indicators in the first and third trimesters were obtained through medical records. The Cox proportional hazards model was used to analyze the association between the coagulation function indicators and PA. A restrictive cubic spline curve was used to draw the dose-response curve between the relevant coagulation function indicators and PA. Results: A total of 1 340 participants were included in this study. The age was (32.50±4.24) and the incidence of PA was 4.4% (59/1 340). After adjusting for relevant factors, Cox proportional hazards model showed that compared with the high-level classification of fibrinogen (FIB), participants within the middle-(HR=3.28, 95%CI: 1.27-8.48) and low-level (HR=3.84, 95%CI: 1.40-10.53) classification during the first trimester and within the low-level classification (HR=4.18, 95%CI: 1.68-10.39) during the third trimester were more likely to experience PA. Compared with the middle-level classification of pro-thrombin time (PT), the risk of PA in the participants within the low-level classification (HR=2.67, 95%CI: 1.48-4.82) was significantly higher in the third trimester. The restrictive cubic spline analysis showed a linear negative association between FIB and PA in the first and third trimesters, while PT and PA showed an approximately L-shaped association . Conclusion: Among pregnant women diagnosed with preeclampsia-eclampsia, the middle-and low-level classification of FIB in the first and third trimesters and the low-level classification of PT in the third trimester could increase the risk of PA.

Analysis of incidence and associated factors of preterm birth based on pre-pregnancy body mass index stratification / 中华预防医学杂志

Objective: To analyze the incidence of preterm birth based on pre-pregnancy body mass index (BMI) stratification and explore the associated factors of preterm birth among pregnant women at different BMI stratifications. Methods: From February 2018 to December 2020, pregnant women who participated in China Birth Cohort Study (CBCS) and gave birth at Beijing Obstetrics and Gynecology Hospital were enrolled as the study subjects. Electronic Data Capture System and standard structured questionnaires were used to collect data related to pre-pregnancy, pregnancy, and delivery for pregnant women. Pregnant women were divided into the low-weight group, normal-weight group and overweight group based on their pre-pregnancy BMI. A Cox proportional hazards model was used to analyze the associated factors of preterm birth among pregnant women with different BMI before pregnancy. Results: A total of 27 195 singleton pregnant women were included, with a preterm birth rate of 5.08% (1 381/27 195). The preterm birth rates in the low-weight group, normal-weight group and overweight group were 4.29% (138/3 219), 4.63% (852/18 390) and 7.00% (391/5 586) respectively (P<0.001). After adjusting for relevant factors, the Cox proportional hazards model showed that the risk of preterm birth in the overweight group was 1.457 times higher than that in the normal-weight group (95%CI: 1.292-1.643). Preeclampsia-eclampsia (HR=2.701, 95%CI: 1.318-5.537) was the associated factor for preterm birth in the low-weight group. Advanced maternal age (HR=1.232, 95%CI: 1.054-1.441), history of preterm birth (HR=4.647, 95%CI: 3.314-6.515), vaginal bleeding in early pregnancy (HR=1.613, 95%CI: 1.380-1.884), and preeclampsia-eclampsia (HR=3.553, 95%CI: 2.866-4.404) were associated factors for preterm birth in the normal-weight group. Advanced maternal age (HR=1.473, 95%CI: 1.193-1.818), history of preterm birth (HR=3.209, 95%CI: 1.960-5.253), vaginal bleeding in early pregnancy (HR=1.636, 95%CI: 1.301-2.058), preeclampsia-eclampsia (HR=2.873, 95%CI:2.265-3.643), and pre-gestational diabetes mellitus (HR=1.867, 95%CI: 1.283-2.717) were associated factors for preterm birth in the overweight group. Conclusion: Pre-pregnancy overweight is an associated factor for preterm birth, and there are significant differences in the associated factors of preterm birth among pregnant women with different BMI before pregnancy.

Relationship between home literacy environment and emotional regulation in children: the mediating effect of the parent-child relationship / 中国当代儿科杂志

OBJECTIVES@#To study the impact of the home literacy environment on children's emotional regulation skills and the mediating role of the parent-child relationship between them.@*METHODS@#A stratified cluster sampling approach was employed to select 1 626 preschool children from five kindergartens in Nanjing. Questionnaires were used to collect detailed information on the home literacy environment, children's emotional regulation skills, and the parent-child relationship. A mediation model was established using the Process program in SPSS macro, and the significance of the mediation effect was tested using the Bootstrap method.@*RESULTS@#The findings revealed a positive correlation between the home literacy environment and children's emotional regulation skills (r=0.217, P<0.001), as well as parent-child intimacy (r=0.065, P<0.01). Conversely, a negative correlation was found between the home literacy environment and parent-child conflict (r=-0.129, P<0.001). Additionally, parent-child conflict demonstrated a negative correlation with children's emotional regulation skills (r=-0.443, P<0.001), while parent-child intimacy exhibited a positive correlation (r=0.247, P<0.001). The home literacy environment exerted a significant direct effect on children's emotional regulation skills (β=0.162, P<0.001), and the mediating effect of the parent-child relationship accounted for 25.54% of the total effect.@*CONCLUSIONS@#The home literacy environment significantly influences children's emotional regulation skills, with the parent-child relationship partially mediating this relationship.

Clinical and genetic analysis of a very early-onset inflammatory bowel disease type 28 child with atypical clinical manifestation / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease (VEO-IBD) type 28 child with atypical clinical manifestations.@*METHODS@#A VEO-IBD type 28 child with atypical clinical manifestations admitted to the Department of Neonatology, Children's Hospital Affiliated to Shandong University on November 5, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 50-day-old male, had manifested bronchitis, ulcerative stomatitis, eczema and slightly loose stool. High-throughput sequencing revealed that he has harbored compound heterozygous variants of the IL-10RA gene, namely c.299T>G (p.V100G) and c.301C>T (p.R101W), which were inherited from his father and mother, respectively. Bioinformatic analysis showed that both variants have been recorded in the HGMD database, though the c.299T>G variant has not been included in the gnomAD, 1000 Genomes, ExAC and ESP6500 databases, while the c.301C>T variant has a low population frequency. Both variants were predicted to be deleterious by the online software including SIFT, PolyPhen-2 and Mutation Taster. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PS3+PM2_Supporting+PP3).@*CONCLUSION@#The c.299T>G and c.301C>T variants of the IL-10RA gene probably underlay the VEO-IBD type 28 in this child. Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.

Comprehensive identification of metabolites and metabolic characteristics of luteolin and kaempferol in Simiao Yong'an Decoction in rats by UHPLC-LTQ-Orbitrap MS/MS / 中国中药杂志

Simiao Yong'an Decoction is a classic prescription for treating gangrene. Modern medical evidence has proven that Si-miao Yong'an Decoction has therapeutic effects on atherosclerosis(AS), vascular occlusion angeitides, and hypertension, while its pharmacodynamic mechanism remains unclear. The evidence of network pharmacology, molecular docking, literature review, and our previous study suggests that luteolin and kaempferol are two major flavonoids in Simiao Yong'an Decoction and can inhibit macrophage inflammation and exert anti-AS effects. However, due to lack of the metabolism studies in vivo, little is known about the metabolic characteristics of luteolin and kaempferol. This study employed ultra-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS/MS) and relevant software to identify the metabolites and metabolic pathways of luteolin and kaempferol in rat plasma, urine, and feces, after oral administration of luteolin and kaempferol, respectively. After the administration of luteolin, 10, 11, and 3 metabolites of luteolin were detected in the plasma, urine, and feces, respectively. After the administration of kaempferol, 9, 3, and 1 metabolites of kaempferol were detected in the plasma, urine, and feces, respectively. The metabolic pathways mainly involved methylation, glucuronidation, and sulfation. This study enriches the knowledge about the pharmacological mechanism of luteolin and kaempferol and supplies a reference for revealing the metabolic process of other flavonoids in Simiao Yong'an Decoction, which is of great significance for elucidating the pharmacological effects and effective substances of this decoction in vivo.

Application and prospect of natural active ingredients of traditional Chinese medicine in immunological adjuvant for influenza vaccine / 中国中药杂志

Vaccination is an effective method for preventing influenza, and adjuvants can enhance the immune response intensity and persistence of influenza vaccines. However, there are currently shortcomings in clinical adjuvant approvals, ineffectiveness against weak antigens, and a tendency to cause headaches. Therefore, the development of safe and effective novel adjuvants for influenza vaccines is particularly important to enhance vaccine immunogenicity and safety. Given the wide range of sources, high safety, and biodegradability of traditional Chinese medicine(TCM), some studies have described it as a vaccine adjuvant. This article reviewed the current status and challenges of influenza vaccine adjuvants, summarized the types of TCM adjuvants, the safety and immunomodulatory effects of natural active ingredients from TCM combined with influenza vaccines, the role of TCM adjuvants in antigen storage, antigen presentation capability, immune cells and cytokines, and immune responses, and analyzed the advantages and disadvantages of TCM adjuvants compared with small molecule adjuvants, with the aim of promoting the clinical development and commercialization of TCM adjuvants for influenza vaccines.

Gender differences in antidepressant effect of raw Rehmanniae Radix / 中国中药杂志

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

Clinical symptoms and distribution characteristics traditional Chinese medicine syndromes of pulmonary nodules / 中国中药杂志

A cross-sectional study method combined with two types of traditional Chinese medicine(TCM) syndrome differentiation methods was adopted to investigate the clinical symptoms and distribution characteristics of TCM syndromes in patients with pulmonary nodules from the perspectives of number, size, nature, and stability of pulmonary nodules by using the χ~2 test, systematic clustering and Apriori algorithm correlation analysis. The common clinical symptoms of pulmonary nodules were fatigue(77.35%) and irritability(75.40%), and 40 symptoms were clustered into 3 groups(digestive system symptoms, respiratory system symptoms, and emotional and systemic symptoms) and 8 major symptom categories. The proportion of cold and heat in complexity syndrome(63.43%) was higher based on cold-heat syndrome differentiation. The top two syndromes were Qi deficiency syndrome(88.03%) and Qi depression syndrome(83.17%) based on disease syndrome differentiation. Yang deficiency syndrome(60.52%) was more than Yin deficiency syndrome(50.16%). There were higher proportions of phlegm syndrome(78.67%) and Yang deficiency syndrome(69.33%) of so-litary pulmonary nodules in terms of the number of pulmonary nodules. In terms of size, the proportion of phlegm syndrome decreased as the mean diameter of pulmonary nodules increased, while the proportions of Yang deficiency syndrome and blood stasis syndrome increased. The distribution of Qi depression syndrome was more in those with mean diameter<10 mm(85.02%, P=0.044) and cold syndrome was more in those with mean diameter ≥10 mm(16.67%, P=0.024). In terms of the nature of pulmonary nodules, the proportions of Qi depression syndrome and heat syndrome decreased with the increase in solid components of pulmonary nodules, while the proportions of Yin deficiency syndrome and cold and heat in complexity syndrome increased. The blood stasis syndrome accounted for a higher proportion of pulmonary nodules with solid components. In terms of the stability of pulmonary nodules, dampness syndrome(72.97%), blood stasis syndrome(37.84%), and cold and heat in complexity syndrome(70.27%) accounted for higher proportions. In addition, patients with new nodules presented higher proportions in Qi inversion syndrome(52.00%, P=0.007) and cold and heat in complexity syndrome(66.00%, P=0.008). Meanwhile, 11 syndromes were associated and 4 common compound syndromes were obtained(Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome). Qi deficiency syndrome and Qi depression syndrome could be associated with other syndromes. The results show that the main clinical symptoms of pulmonary nodules are fatigue and irritability. The main TCM syndromes of pulmonary nodules are Qi deficiency syndrome, Qi depression syndrome, Yang deficiency syndrome, and cold and heat in complexity syndrome. The distribution of TCM syndromes is significantly correlated with the size of pulmonary nodules and the presence or absence of new nodules. The common compound syndromes are Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome.

Mechanism of albiflorin in improvement of Alzheimer's disease based on network pharmacology and in vitro experiments / 中国中药杂志

This study aimed to explore the mechanism of albiflorin in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking, and in vitro experiments. Network pharmacology was used to predict the potential targets and pathways of albiflorin against AD, and molecular docking technology was used to verify the binding affinity of albiflorin to key target proteins. Finally, the AD cell model was induced by Aβ_(25-35) in rat pheochromocytoma(PC12) cells and intervened by albiflorin to validate core targets and pathways. The results of network pharmacological analysis showed that albiflorin acted on key targets such as mitogen-activated protein kinase-1(MAPK1 or ERK2), albumin(ALB), epidermal growth factor receptor(EGFR), caspase-3(CASP3), and sodium-dependent serotonin transporter(SLC6A4), and signaling pathways such as MAPK, cAMP, and cGMP-PKG. The results of molecular docking showed that albiflorin had strong binding affinity to MAPK1(ERK2). In vitro experiments showed that compared with the blank group, the model group showed decreased cell viability, decreased expression level of B-cell lymphoma 2(Bcl-2), increased Bcl-2-associated X protein(Bax), and reduced phosphorylation level of extracellular signal-regulated kinase 1/2(ERK1/2) and the relative expression ratio of p-ERK1/2 to ERK1/2. Compared with the model group, the albiflorin group showed potentiated cell viability, up-regulated expression of Bcl-2, down-regulated Bax, and increased phosphorylation level of ERK1/2 and the relative expression ratio of p-ERK1/2 to ERK1/2. These results suggest that the mechanism of albiflorin against AD may be related to its activation of the MAPK/ERK signaling pathway and its inhibition of neuronal apoptosis.

25G pars plana vitrectomy combined with Dexamethasone intravitreal implants for the treatment of vitreous hemorrhage and diabetic macular edema secondary to proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical effect of 25G pars plana vitrectomy(PPV)combined with dexamethasone intravitreal implant(DEX)on the treatment of vitreous hemorrhage and diabetic macular edema(DME)secondary to proliferative diabetic retinopathy(PDR).METHODS: Prospective clinical case study. A total of 40 patients(40 eyes)with vitreous hemorrhage and DME secondary to PDR who treated in Tianjin Eye Hospital from July 2020 to January 2022 were included in the study. All eyes underwent 25G PPV and cataract phacoemulsification. The patients were randomly divided into PPV group(20 eyes)and PPV+DEX group(20 eyes). Best corrected visual acuity(BCVA), intraocular pressure, and central macular thickness(CMT)of the patients before and 1, 3, 6mo after the operation were compared.RESULTS: All patients were followed up for 6mo. The BCVA of the patients in the PPV+DEX group improved better than that of the PPV group at 1, 3 and 6mo after surgery(P&#x003C;0.05). CMT of the PPV+DEX group was lower than that of the PPV group at 1mo after operation(P&#x003C;0.05). Retinal neovascularization or CMT regression with less than 5% was found in 8 eyes in the PPV group, who were supplemented with anti-vascular endothelial growth factor, while it was found in only 1 eye in the PPV+DEX group(P&#x003C;0.05).CONCLUSION: PPV combined with DEX could yield synergies, which provide better therapeutic effect for the patients with vitreous hemorrhage and DME secondary to PDR.