Knowledge Graph Enhanced Transformers for Diagnosis Generation of Chinese Medicine / 中国结合医学杂志

Chinese medicine (CM) diagnosis intellectualization is one of the hotspots in the research of CM modernization. The traditional CM intelligent diagnosis models transform the CM diagnosis issues into classification issues, however, it is difficult to solve the problems such as excessive or similar categories. With the development of natural language processing techniques, text generation technique has become increasingly mature. In this study, we aimed to establish the CM diagnosis generation model by transforming the CM diagnosis issues into text generation issues. The semantic context characteristic learning capacity was enhanced referring to Bidirectional Long Short-Term Memory (BILSTM) with Transformer as the backbone network. Meanwhile, the CM diagnosis generation model Knowledge Graph Enhanced Transformer (KGET) was established by introducing the knowledge in medical field to enhance the inferential capability. The KGET model was established based on 566 CM case texts, and was compared with the classic text generation models including Long Short-Term Memory sequence-to-sequence (LSTM-seq2seq), Bidirectional and Auto-Regression Transformer (BART), and Chinese Pre-trained Unbalanced Transformer (CPT), so as to analyze the model manifestations. Finally, the ablation experiments were performed to explore the influence of the optimized part on the KGET model. The results of Bilingual Evaluation Understudy (BLEU), Recall-Oriented Understudy for Gisting Evaluation 1 (ROUGE1), ROUGE2 and Edit distance of KGET model were 45.85, 73.93, 54.59 and 7.12, respectively in this study. Compared with LSTM-seq2seq, BART and CPT models, the KGET model was higher in BLEU, ROUGE1 and ROUGE2 by 6.00-17.09, 1.65-9.39 and 0.51-17.62, respectively, and lower in Edit distance by 0.47-3.21. The ablation experiment results revealed that introduction of BILSTM model and prior knowledge could significantly increase the model performance. Additionally, the manual assessment indicated that the CM diagnosis results of the KGET model used in this study were highly consistent with the practical diagnosis results. In conclusion, text generation technology can be effectively applied to CM diagnostic modeling. It can effectively avoid the problem of poor diagnostic performance caused by excessive and similar categories in traditional CM diagnostic classification models. CM diagnostic text generation technology has broad application prospects in the future.

Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities / 中国肺癌杂志

BACKGROUND@#In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.@*METHODS@#A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.@*RESULTS@#MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).@*CONCLUSIONS@#The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.

Identification and expression analysis of cellulose synthase family genes in Aquilaria sinensis / 药学学报

Cellulose synthase (CesA), one of the key enzymes in the biosynthesis of cellulose in plants, plays an important role in plant growth and plant resistance. In this study, a total of 21 AsCesA genes from Aquilaria sinensis were systematically identified and the physico-chemical characteristics were analyzed based on genome database and bioinformatical methods. The phylogenetic tree was constructed and the gene location on chromosome, cis-acting elements in the 2 000 basepairs upstream regulatory regions and conservative motifs were analyzed. The AsCesA proteins were mainly located on the plasma membrane. The number of amino acids of the proteins ranged from 390 to 1 261. The isoelectric point distributed from 5.67 to 8.86. All of the 21 AsCesA proteins possessed the transmembrane domains, the number of which was from 6 to 8. The genes were classified into 3 groups according to the phylogenetic relationship. Obvious differences were observed in motif composition in genes from different groups. However, motif2, motif6, motif7 and motif10 were observed in all of AsCesA proteins. Analysis of cis-acting elements indicated that AsCesA genes family has cis-acting elements related to plant hormones, abiotic stresses, and biological processes. Seven AsCesA genes with differential expression were selected according to the calli transcriptome data induced by NaCl at different times and their expression levels under different abiotic stresses were analyzed by quantitative real-time PCR. The results indicated that salt, low temperature, drought, and heavy metal stresses could affect the expression level of AsCesA genes, and the abundance of AsCesA1, AsCesA3 and AsCesA20 showed a significant change, implying their potential important roles to the abiotic stresses. The accumulation pattern of cellulose content under different abiotic stresses was similar to the expression trend of AsCesA genes. Our results provide valuable insights into the role of cellulose synthase in A.sinensis in plant defense.

Study on the antitussive and expectorant activities and mechanism of platycodin D based on metabolomics method / 药学学报

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.

Comparison of 17β-estradiol against retinal light damage in BALB/c or C57BL/6 mice / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the neuroprotective effect of 17β-estradiol(E2)on retina light damage in BALB/c and C57BL/6 mice and provide experimental data for the successful construction of a research model for E2 against retinal light damage.METHODS:Totally 40～45 adult female BALB/c or C57BL/6 mice were divided into six groups, 6 for each group: normal control, ovariectomized control, ovariectomized light(mice were stimulated with continuous white light at 10000 lx for 4, 8, 12, 16, and 24h after 14d of ovariectomy), intravitreal administration sham operation, saline and E2 pre-treatment groups(2μL saline or 10-5mol/L E2 were intravitreal injected respectively after 14d of ovariectomy operation and 24h of dark adaptation). The morphological and functional changes of the retina were detected by paraffin section HE staining, TUNEL staining and electroretinogram.RESULTS:In the ovariectomized light group, the thickness of the inner/outer nuclear layer decreased significantly from the 4h stimulation of 10000 lx white light group. Intravitreal administration of E2 significantly inhibited the apoptosis of retinal cells in the two strains of mice(P&#x003C;0.01)and the decrease of amplitudes of a- and b-waves in max-ERG of C57BL/6 mice(P&#x003C;0.05).CONCLUSION:The light loss sensitivity of two strains of mice was different under the same light stimulation. E2 had a protective effect on both morphology and function of the retina in BALB/c mice, and had a significant protective effect on retina function in C57BL/6 mice.

The status and trend of child growth failure (CGF) burden in children aged < 5 years in China / 公共卫生与预防医学

Objective To analyze the status and trend for the mortality and DALY rates of child growth failure (CGF) in children aged < 5 years in China from 1990 to 2019, so as to provide a scientific basis for CGF prevention and control. Methods The mortality and DALY rates of CGF in children aged < 5 years from 1990 to 2019 were obtained from GBD 2019. The changes of these indicators with the years in China , the United States, Japan, Russia, India and the global were compared and analyzed. Results In 2019, the mortality of child wasting, child stunting and child underweight in children aged < 5 years in China were 9.62/100 000, 1.23/100 000, and 1.29/100 000 respectively, the mortality rates were 867.50/100 000 , 129.23/100 000 , and 112.87/100 000 rescpectively, higher than those of the United States, Japan, and Russia, and far lower than those of India and the global. The disease burden of three types of CGF were all higher in males than females, and higher in children aged < 1 years than children aged 1-4 years. From 1990 to 2019, the mortality and DALY rates of CGF in children aged < 5 years in China decreased from 300.41/100 000 and 26 445.38/100 000 to 10.49/100 000 and 943.57/100 000, respectively. China had the largest drop rate compared with all analyzed countries. As for children aged < 5 years in China, the DALY rate of lower respiratory infection ranked first in all the diseases caused by CGF. Conclusion From 1990 to 2019, the disease burden of CGF in children aged < 5 years has shown a significant decrease in China , but it is still far behind the developed countries. In the future, more attention should be paid to the problems of child growth in hope of reducing the mortality and DALY rates of CGF.

Whole-course management strategies for gastroesophageal reflux disease: an evidence mapping study based on clinical practice guidelines / 中华胃肠外科杂志

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases with high incidence, complicated clinical symptoms, difficulties in standard treatment, and heavy medical burden. At present, some GERD-relevant clinical practice guidelines (CPGs) have been issued by different countries and academic organizations, but some recommendations were inconsistent, which has caused some problems for the current clinical whole-course management of GERD. To summarize the relevant evidence among the CPGs on GERD and formulate the whole- course management strategies, we included GERD-relevant CPGs published or updated after 2010 by searching websites of guidelines, relevant professional societies, and electronic databases. We extracted the recommendations and summarized the evidence from the aspects of symptoms, epidemiology, diagnosis and treatment, which was presented in the form of evidence mapping. We included 24 CPGs, including three in Chinese and 21 in English. The clinical practice management strategies of GERD were formulated based on the evidence from the aspects of clinical symptoms, diagnostic methods, medical treatment, anti-reflux surgery and endoscopic treatment, psychological treatment, and traditional Chinese medicine treatment.

Efficacy and safety of sacubitril/valsartan after six months in patients with heart failure with reduced ejection fraction and asymptomatic hypotension / 老年心脏病学杂志（英文版）

BACKGROUND@#It is not clear whether sacubitril/valsartan is beneficial for patients with heart failure (HF) with reduced ejection fraction (HFrEF) and low systolic blood pressure (SBP). This study aimed to investigate the efficacy and tolerability of sacubitril/valsartan in HFrEF patients with SBP < 100 mmHg.@*METHODS & RESULTS@#An observational study was conducted on 117 patients, 40.2% of whom had SBP < 100 mmHg without symptomatic hypotension, and 59.8% of whom had SBP ≥ 100 mmHg in an optimized HF follow-up management system. At the 6-month follow-up, 52.4% of patients with SBP < 100 mmHg and 70.0% of those with SBP ≥ 100 mmHg successfully reached the target dosages of sacubitril/valsartan. A reduction in the concentration of N-terminal pro-B-type natriuretic peptide was similar between patients with SBP < 100 mmHg and SBP ≥ 100 mmHg (1627.5 pg/mL and 1340.1 pg/mL, respectively; P = 0.75). The effect of sacubitril/valsartan on left ventricular ejection fraction was observed in both SBP categories, with a 10.8% increase in patients with SBP < 100 mmHg (P < 0.001) and a 14.0% increase in patients with SBP ≥ 100 mmHg (P < 0.001). The effects of sacubitril/valsartan on SBP were statistically significant and inverse across both SBP categories (P = 0.001), with an increase of 7.5 mmHg in patients with SBP < 100 mmHg and a decrease of 11.5 mmHg in patients with SBP ≥ 100 mmHg. No statistically significant differences were observed between the two groups in terms of the occurrence of symptomatic hypotension, deteriorating renal function, hyperkalemia, angioedema, or stroke.@*CONCLUSIONS@#Within an optimized HF follow-up management system, sacubitril/valsartan exhibited excellent tolerability and prompted left ventricular reverse remodeling in patients with HFrEF who presented asymptomatic hypotension.

Multiple portions enteral nutrition and chyme reinfusion of a blunt bowel injury patient with hyperbilirubinemia undergoing open abdomen: A case report / 中华创伤杂志(英文版)

Blunt bowel injury (BBI) is relatively rare but life-threatening when delayed in surgical repair or anastomosis. Providing enteral nutrition (EN) in BBI patients with open abdomen after damage control surgery is challenging, especially for those with discontinuity of the bowel. Here, we report a 47-year-old male driver who was involved in a motor vehicle collision and developed ascites on post-trauma day 3. Emergency exploratory laparotomy at a local hospital revealed a complete rupture of the jejunum and then primary anastomosis was performed. Postoperatively, the patient was transferred to our trauma center for septic shock and hyperbilirubinemia. Following salvage resuscitation, damage control laparotomy with open abdomen was performed for abdominal sepsis, and a temporary double enterostomy (TDE) was created where the anastomosis was ruptured. Given the TDE and high risk of malnutrition, multiple portions EN were performed, including a proximal portion EN support through a nasogastric tube and a distal portion EN via a jejunal feeding tube. Besides, chyme delivered from the proximal portion of TDE was injected into the distal portion of TDE via a jejunal feeding tube. Hyperbilirubinemia was alleviated with the increase in chyme reinfusion. After 6 months of home EN and chyme reinfusion, the patient finally underwent TDE reversal and abdominal wall reconstruction and was discharged with a regular diet. For BBI patients with postoperative hyperbilirubinemia who underwent open abdomen, the combination of multiple portions EN and chyme reinfusion may be a feasible and safe option.

PROSI Mutation With Clinical Heterogeneity in Protein S Deficiency:Report of One Case / 中国医学科学院学报

Reduced protein S activity is one of the high-risk factors for venous thromboembolism.Hereditary protein S deficiency is an autosomal dominant disorder caused by mutations in the PROS1 gene.We reported a female patient with a mutation of c.292 G>T in exon 3 of the PROS1 gene,which was identified by sequencing.The genealogical analysis revealed that the mutation probably originated from the patient's mother.After searching against the PROS1 gene mutation database and the relevant literature,we confirmed that this mutation was reported for the first time internationally.

The Psychosomatic Traits of "People with the Five Elements in Traditional Chinese Medicine": A Qualitative Study / 生物医学与环境科学（英文）

OBJECTIVE@#To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of "people with the five elements in traditional Chinese medicine (TCM)."@*METHODS@#Data collected from the literature review, two sessions of brainstorming of experts with related experience in "people with the five elements in TCM" from October 2020 to December 2020, and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed. Triangulation was used in this study, and theming and synthesizing were used to analyze the data.@*RESULTS@#A total of 31 experts and 30 interviewees participated in this study. The median age of the experts and interviewees were 48.0 and 38.5 years, respectively; 51.66% and 54.8% of experts and interviewees, respectively, were men. The descriptors of facial diagrams of "people with the five elements in TCM" were complexion, shape, distribution state of facial bones, convergence trend of facial muscles, and facial expression. A theoretical model of "people with the five elements in TCM" was shaped based on these findings.@*CONCLUSION@#The study suggests a possibility for bridging the gap between personality and bodily state, identifying an avenue for personality research from the perspective of TCM.

Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature / 生物医学与环境科学（英文）

OBJECTIVE@#Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery.@*METHODS@#We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated.@*RESULTS@#A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery.@*CONCLUSION@#These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.

Panax notoginseng saponins improve monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting ADAM10/Notch3 signaling pathway / 生理学报

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.

Research progress on the effect mechanism of acupuncture-moxibustion for pressure injuries / 中国针灸

Evidence shows that acupuncture-moxibustion could promote the healing of pressure injuries (PI), but its action mechanism is not fully understood. This review summarizes the basic research literature of acupuncture-moxibustion for PI and identifies that the mechanism of acupuncture-moxibustion for PI is related with regulation of related signaling pathway target proteins, improvement of inflammatory response, modulation of vascular microenvironment, attenuation of oxidative stress damage, and inhibition of cell apoptosis. The review also points out the current limitations and future research directions. It emphasizes the need for further exploration of the upstream regulatory mechanism, specific cellular molecules, and the interactions among these molecules. A multi-level, multi-target, and multi-dimensional approach is required to fully understand the mechanism underlying the promotion of PI healing by acupuncture-moxibustion.

Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis

Background/Aims@#Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. @*Methods@#We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. @*Results@#We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). @*Conclusions@#IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Histamine H / 中国药理学通报

Aim To determine the effect of histamine H

Poisonous substances and geographical distribution of poisoning in hospitalized children based on data from 25 hospitals in China from 2016 to 2020 / 中华儿科杂志

Objective: To investigate the poisonous substances and geographical distribution of poisoning in children in China. Methods: A cross-sectional study. The clinical data of 8 385 hospitalized children from January 2016 to December 2020 were extracted from the FUTang Updating Medical Records database. These children aged 0 to 18 years and were admitted due to poisoning. They were grouped according to age (newborns and infants, toddlers, preschoolers, school-age children, adolescents), place of residence (Northeast China, North China, Central China, East China, South China, Southwest China, Northwest China), and mode of discharge (discharge under medical advice, transfer to another hospital under medical advice, discharge without medical advice, death, other). The poisonous substance and causes of poisoning in different groups were analyzed. Results: Among these 8 385 children, 4 734 (56.5%) were male and 3 651 (43.5%) female, with a male-to-female ratio of 1.3∶1. The age was 3 (2, 7) years. The prevalence of poisoning was 51.8% (4 343/8 385) in toddlers, 16.5% (1 380/8 385) in adolescents, 14.8% (1 242/8 385) in preschoolers, 14.4% (1 206/8 385) in school-age children, and 2.5% (214/8 385) in newborns and infants. Drug poisoning accounted for 43.5% (3 649/8 385) and pesticide accounted for 26.8% (2 249/8 385). Drug poisoning was more common in adolescents (684/1 380, 49.6%) and toddlers (2 041/4 343, 47.0%); non-drug poisoning was more common in school-age children (891/1 206, 73.9%), of which carbon monoxide was mainly in newborns and infants (41/214, 19.2%) and food poisoning in children of school age (241/1 206, 20.0%). Regarding regional characteristics, drug poisoning was more frequent in South China (188/246, 64.2%) and non-drug poisoning was more frequent in Southwest China (815/1 123, 72.5%). For drugs, anti-epileptic drugs, sedative-hypnotic drugs and anti-Parkinson's disease drugs had a higher proportion of poisoning in North China (138/1 034, 13.0%) than that in other regions. For non-drug poisoning, pesticides (375/1 123, 33.3%), food poisoning (209/1 123, 18.6%) and contact with poisonous animals (86/1 123, 7.7%) were more common in Southwest China than in other regions; carbon monoxide poisoning was more common in North China (81/1 034, 7.6%) and Northwest China (65/1 064, 6.3%). In Central China, poisoning happened more in toddlers (792/1 295, 61.2%) and less in adolescents (115/1 295, 8.8%) than in other regions. Regarding different age groups, poisoning in adolescent happened more in Northeast China (121/457, 26.5%), North China (240/1 034, 23.2%), and Northwest China (245/1 064, 23.0%). The rate of discharge under medical advice, discharge without medical advice, and mortality rate within the 5 years were 77.0% (6 458/8 385), 20.8% (1 743/8 385), 0.5% (40/8 385), respectively. Conclusions: Poisoning is more common in male and toddlers. Poisonous substances show a regional characteristic and vary in different age groups, with drugs and insecticides as the most common substances.

Lipid peroxidation changes induced by dibutyl phthalate in allergic asthma mice / 环境与职业医学

Background Dibutyl phthalate (DBP) is a common plasticizer in daily life and has been proved to be related to the exacerbation of allergic asthma. Domestic and foreign studies have shown that lipid peroxidation is closely related to the severity of asthma, which can be used as a basis for the diagnosis and treatment of asthma. Whether DBP can induce lipid peroxidation in allergic asthma remains to be further studied. Objective To investigate whether DBP aggravates allergic asthma by inducing lipid peroxidation in allergic asthma mice. Methods Eighty male BALB/c mice were randomly divided into 4 groups, namely control group, DBP group (40 mg·kg−1), 50 μg ovalbumin (OVA) group (allergic asthma model group), and DBP+OVA group. The DBP group and the DBP+OVA group were given DBP by gavage from Day 1 to 28, and the OVA group and the DBP+OVA group were sensitized by intraperitoneal injection of OVA, once every 3 d, a total of 5 injections, from Day 9 to 21. From Day 29 to 35, the OVA group and the DBP+OVA group were challenged by OVA atomization. After the exposure, samples of blood and lung were collected. The airway hyperresponsiveness of mice was observed by lung function analysis. The serum contents of immunoglobulin E (IgE), OVA-specific immunoglobulin E (OVA-IgE), and lung homogenate levels of interleukin 4 (IL-4) were detected by enzyme-linked immunosorbent assay (ELISA) to evaluate airway allergic inflammation. The pathological changes of lung tissues were observed after hematoxylin-eosin (HE) staining and collagen fiber (Masson) staining. The contents of reactive oxygen species (ROS), lipid ROS, glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) in lung homogenates were detected by ELISA to evaluate lipid peroxidation. Results The results of lung function analysis showed that compared with the control group, the inspiratory resistance (Ri) and expiratory resistance (Re) of the OVA group and the DBP+OVA group were increased, and the lung compliance (Cldyn) was decreased. The DBP + OVA group was more severe, and the difference between the OVA group and the DBP + OVA group was statistically significant (P<0.05 or P<0.01). Compared with the control group, the contents of IgE, OVA-IgE, and IL-4 in the OVA group and the DBP+OVA group were increased (P<0.05 or P<0.01), which indicated more severe allergic airway inflammation. The HE sections of the OVA group and the DBP+OVA group showed inflammatory cell infiltration around the airway, airway wall hyperplasia and thickening, and severe airway deformation, and the presentation of the DBP+OVA group was the most serious. After Masson staining, the OVA group and the DBP+OVA group showed depositions of a large number of collagen fibers, and the blue collagen fibrosis in the DBP+OVA group was even more serious. ROS, lipid ROS, MDA, and 4-HNE levels increased and GSH and GPX4 levels decreased in the OVA and DBP+OVA groups (P<0.05 or P<0.01), with the most severe effect in the DBP+OVA group. Conclusion DBP may induce lipid peroxidation in mice allergic asthma by producing excessive ROS which may aggravate the allergic asthma in mice.

Significance of high expression of C5orf46 in gastric cancer and potential intervention of tarditional Chinese medicine based on bioinformatics, molecular docking, and cell experiments / 中国中药杂志

This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 μmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.

Cloning, expression analysis and enzyme activity verification of dihydroflavonol 4-reductase from Cistanche tubulosa (Schenk) Wight flower / 药学学报

Dihydroflavonol 4-reductase (DFR) plays an essential role in the biosynthesis of anthocyanin and regulation of plant flower color. Based on the transcriptome data of Cistanche tubulosa (Schenk) Wight, a full-length cDNA sequence of CtDFR gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR). CtDFR contains an open reading frame (ORF) of 1 263 bp which encodes 420 amino acids with a predicted molecular weight of 47.5 kDa. The sequence analysis showed that CtDFR contains a nicotinamide adenine dinucleotide phosphate (NADPH) binding domain and a specific substrate binding domain. The expression analysis indicated that CtDFR was highly expressed in red and purple flowers, and the relative expression levels were 4.04 and 19.37 times higher than those of white flowers, respectively. The recombinant CtDFR protein was expressed in E.coli BL21 (DE3) using vector pET-28a-CtDFR and was purified. In vitro enzyme activity analysis, CtDFR could reduce three types of dihydroflavonols including dihydrokaempferol, dihydroquercetin, and dihydromyricetin to leucopelargonidin, leucocyanidin and leucodelphinidin. Subcellular localization analysis showed that CtDFR was mainly localized in the cytoplasm. These results demonstrate that CtDFR plays an important role in regulation of flower color in C. tubulosa and make a valuable contribution for the further investigation on the regulation mechanism of C. tubulosa (Schenk) Wight flower color.