Protective effect of intervention with cannabinoid type-2 receptor agonist JWH133 on pulmonary fibrosis in mice / 中华内科杂志

Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) μg/mg vs. (0.974±0.060) μg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) μg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.

Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction / 中国结合医学杂志

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.

Effect of Nucleolin on Lymphoma Proliferation by Regulating Thymidine Kinase 1 / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of nucleolin (NCL) involved in lymphoma proliferation by regulating thymidine kinase 1 (TK1).@*METHODS@#Twenty-three patients with diffuse large B-cell lymphoma (DLBCL) were selected and divided into initial treatment group (14 cases) and relapsed/refractory group (9 cases). Serum TK1 and C23 protein in peripheral blood mononuclear cells were detected. Cell models of CA46-NCL-KD (CA46-NCL-knockdown) and CA46-NCL-KNC (CA46-NCL-knockdown negative control) were established by lentivirus vector mediated transfection in Burkitt lymphoma cell line CA46. The half maximal inhibitory concentration (IC50) of CA46-NCL-KD, CA46-NCL-KNC, and CA46 to adriamycin were detected by cell proliferation assay (MTS). The expression of NCL mRNA and protein in CA46-NCL-KD and CA46-NCL-KNC cells were dectected by Q-PCR and Western blot, respectively. The cell cycle of CA46-NCL-KD, CA46-NCL-KNC, and CA46 cells were detected by flow cytometry. The expression of TK1 protein in CA46-NCL-KD and CA46-NCL-KNC cells was detected by an enhanced chemiluminescence (ECL) dot blot assay.@*RESULTS@#The level of serum TK1 in the initial treatment group was 0.43(0-30-1.01) pmol/L, which was lower than 10.56(2.19-14.99) pmol/L in the relapsed/refractory group (P<0-01), and the relative expression level of NCL protein in peripheral blood was also significantly lower. The IC50 of CA46-C23-KD cells to adriamycin was (0.147±0.02) μg/ml, which was significantly lower than (0.301±0.04) μg/ml of CA46-C23-KNC cells and (0.338±0.05) μg/ml of CA46 cells (P<0.05). Compared with CA46-NCL-KNC cells, the expression of NCL mRNA and protein, TK1 protein decreased in CA46-NCL-KD cells, and the proportion of S phase and G2/M phase also decreased, while G0/G1 phase increased in cell cycle.@*CONCLUSION@#The increased expression of NCL in DLBCL and CA46 cells indicates low sensitivity to drug. NCL may participate in regulation of lymphoma proliferation by affecting TK1 expression, thereby affecting the drug sensitivity.

Clinical Features and Prognosis of Multiple Myeloma Patients with Secondary Primary Malignancies / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies.@*METHODS@#The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated.@*RESULTS@#A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027).@*CONCLUSION@#The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.

Physiological and biochemical mechanisms of brassinosteroid in improving anti-cadmium stress ability of Panax notoginseng / 中国中药杂志

In this study, the effect of brassinosteroid(BR) on the physiological and biochemical conditions of 2-year-old Panax notoginseng under the cadmium stress was investigated by the pot experiments. The results showed that cadmium treatment at 10 mg·kg~(-1) inhibited the root viability of P. notoginseng, significantly increased the content of H_2O_2 and MDA in the leaves and roots of P. noto-ginseng, caused oxidative damage of P. notoginseng, and reduced the activities of SOD and CAT. Cadmium stress reduced the chlorophyll content of P. notoginseng, increased leaf F_o, reduced F_m, F_v/F_m, and PIABS, and damaged the photosynthesis system of P. notoginseng. Cadmium treatment increased the soluble sugar content of P. notoginseng leaves and roots, inhibited the synthesis of soluble proteins, reduced the fresh weight and dry weight, and inhibited the growth of P. notoginseng. External spray application of 0.1 mg·L~(-1) BR reduced the H_2O_2 and MDA content in P. notoginseng leaves and roots under the cadmium stress, alleviated cadmium-induced oxidative damage to P. notoginseng, improved the antioxidant enzyme activity and root activity of P. notoginseng, increased the content of chlorophyll, reduced the F_o of P. notoginseng leaves, increased F_m, F_v/F_m, and PIABS, alleviated the cadmium-induced damage to the photosynthesis system, and improved the synthesis ability of soluble proteins. In summary, BR can enhance the anti-cadmium stress ability of P. notoginseng by regulating the antioxidant enzyme system and photosynthesis system of P. notoginseng under the cadmium stress. In the context of 0.1 mg·L~(-1) BR, P. notoginseng can better absorb and utilize light energy and synthesize more nutrients, which is more suitable for the growth and development of P. notoginseng.

Effect of superfine powder and aqueous extract of Polygonati Rhizoma on rats with natural perimenopausal syndrome / 中国中药杂志

This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, β-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.

Clinical characteristics of children with 2019 novel coronavirus infection in Putian City / 中华传染病杂志

Objective:To analyze the clinical characteristics of children with 2019 novel coronavirus (2019-nCoV) infection in Putian City, and to provide a reference for the diagnosis and treatment of children with 2019-nCoV infection.Methods:Clinical characteristics, laboratory examination, pulmonary compated tomography findings, treatment, and clinical outcomes of 78 children with 2019-nCoV infection who were admitted to Putian University Affiliated Hospital Medical Group Putian City Children′s Hospital from September 10 to October 20, 2021 were retrospectively collected and analyzed.Results:Of the 78 children included in the analysis, two cases (2.6%) were asymptomatic infection, 36 cases (46.2%) were mild and 40 cases (51.3%) were ordinary. Five children were vaccinated against 2019-nCoV. The main symptoms were fever (24 cases), cough (13 cases), and fatigue (nine cases). A total of 34 cases (43.6%) had neutropenia, 29 cases (37.2%) had lymphopenia, 36 cases (46.2%) had D-dimer increase, 38 cases (48.7%) had hypokalemia, 27 cases (34.6%) had hypoglycemia and 11 cases (14.1%) had elevated creatine kinase isoenzyme. The neutropenia mostly occurred two to four days after admission. Fifty-six cases (71.8%) showed pulmonary computed tomography abnormalities. The cycle threshold of virus open reading frame ( ORF)1 ab was 20.90±7.15 and the cycle threshold of N gene was 20.29±7.78 in the first nucleic acid detection of 78 children after admission. The time of nucleic acid negative conversion of the 78 children was (20.73±6.94) days. IgM antibody titer in five vaccinated children was 0.36 (0.34, 4.89) and IgG antibody was 10.42 (0.50, 19.42). IgM antibody titer was 1.82 (1.66, 8.12) and IgG antibody was 76.63 (16.92, 79.84) in cases with disease duration ≥10 days. Nine children (11.5%) had resurgence of virus and were sent to the isolation site. All the other children were cured and discharged from hospital. Conclusions:Children with 2019-nCoV infection have mild clinical symptoms, and some children have lymphopenia, neutropenia, and D-dimer elevation during the course of the disease. The overall prognosis is good. The children vaccinated against 2019-nCoV have higher antibody levels.

Study on genetics and early diagnosis of early onset epileptic encephalopathy of unknown etiology / 中华实用儿科临床杂志

Objective:To explore the genetic etiology and the value of early diagnosis of early onset epileptic encephalopathy (EOEE) with unknown etiology.Methods:A total of 60 children with EOEE of unknown etiology were prospectively enrolled in the outpatient and inpatient departments of Fujian Provincial Hospital from January 2018 to January 2021.Peripheral blood was collected prospectively for whole-exome sequencing and copy number variation (CNV) detection to analyze the clinical characteristics and genetic sequencing results of the children.Results:Twenty-four patients with EOEE-related pathogenic or suspected pathogenic mutations were detected, including infantile spasms (10 cases), Dravet syndrome (3 cases), pyridoxine-dependent epilepsy (1 case) and ohtahara syndrome (1 case), and unknown epileptic encephalopathy (9 cases). The onset age of EOEE-related patients ranged from 1 day to 11 months (median age was 4.2 months), the treatment age ranged from 2 days to 4 years (median age was 10 months), and the age of diagnosis was controlled within 1 month after treatment.There were 20 cases (33.3%) single gene variants and 4 cases (6.7%) CNV variants.A total of 13 genes were involved: KCNQ2, SCN1A, SCN8A, CACNA1E, CDKL5, PPP3CA, PCDH19, TSC1, TSC2, ZEB2, ALDH7A1, DCX and HNRNPU.The 4 CNV abnormalities were 17p13.3 deletion, 11q23.3q25 deletion, 1q36.31-p36.33 deletion, 1q43-1q44 deletion and Xp22.33 duplication, respectively.Totally, 20 mutations were new loci reported for the first time at home and abroad; 11q23.3q25 deletion that resulted in infantile spasm was first reported at home and abroad.Infantile spasm caused by ZEB2 mutation and epileptic encephalopathy caused by PPP3CA gene were both reported for the first time in China. Conclusions:Gene and CNV are important potential causes of children suffering from EOEE.When the etiology is unclear, the combination of whole-exome sequencing and CNV sequencing technology can improve the diagnosis level of genetic etiology of children with EOEE.The early genetic detection of these children can early diagnose and accurately treat epilepsy.

Tumor microenvironment responsive liposomes blocking CXCL12/CXCR4 pathway and synergistically enhancing immune efficacy of anti-PD-L1 / 药学学报

Blocking immune checkpoint programmed cell death receptor 1 (PD-1) or programmed death receptor-ligand 1 (PD-L1) can enhance anti-tumor activity of effector T cells. However, the lack of response in many patients to PD-1/PD-L1 therapy remains a question. Improving the immunosuppressive tumor microenvironment (TME) to enhance the efficacy of immune checkpoint inhibitors has become a promising cancer treatment strategy. We constructed a liposome system (PD-L1/siCXCL12-Lp) of CXCL12 siRNA and anti-PD-L1 peptide with matrix metalloproteinases (MMPs) responsiveness, which combined the TME regulation of siCXCL12 and the immune regulation of anti-PD-L1 peptide. All animal experiments were approved by the Biomedical Ethics Committee of Peking University. The authors found that PD-L1/siCXCL12-Lp directly down-regulated the expression of CXCL12 in vitro (33.8%) and in vivo (15.5%). It also effectively increased the ratio of CD8+/Treg by 20.0%, which helped the anti-PD-L1 peptide to better exert its immune effect. The combination therapy significantly inhibited tumor growth (52.08%) with great safety, which explored a new idea for cancer immunotherapy.

Effectiveness of training on Taenia solium taeniasis and cysticercosis control knowledge among medical professionals in disease-elimination pilot areas of Henan Province / 中国血吸虫病防治杂志

Objective To investigate the changes in the awareness rate of Taenia solium taeniasis and cysticercosis control knowledge among medical professionals before and after training in Fangcheng County, a disease-elimination pilot area of Henan Province, so as to evaluate the effectiveness of the training. Methods Three townships in Fangcheng County were randomly selected as the study townships, including Dushu, Bowang and Yangji townships, while Erlangmiao, Yanglou and Xiaoshidian townships in the county were randomly selected as the control townships. The grassroots medical professionals in the study townships were given once training on T. solium taeniasis and cysticercosis control knowledge each year from 2016 to 2020, while those in the control townships were given no interventions. All village-level doctors and a part of township-level public health professionals were sampled from the study and control townships as intervention and control groups. The baseline and final assessments of the awareness of T. solium taeniasis and cysticercosis control knowledge were performed using questionnaire survey in intervention and control groups in 2016 and 2020, and the awareness of T. solium taeniasis and cysticercosis control knowledge was compared between the two groups. Results A total of 663 medical professionals were investigated in Fangcheng County from 2016 to 2020, including 474 participants in the intervention group and 189 participants in the control group. Results from the 2016 baseline survey showed that the awareness rate of T. solium taeniasis and cysticercosis control knowledge was 28.83% (47/163) among grassroots medical professionals in Fangcheng County, and there were no significant differences in the awareness between the intervention (32.47%, 25/77) and control groups (25.58%, 22/86) (χ2 = 0.939, P > 0.05), between men (30.50%, 43/141) and women (18.18%, 4/22) (χ2 = 1.406, P > 0.05) or between village- (31.39%, 43/137) and township-level medical professionals (15.38%, 4/26) (χ2 = 2.727, P > 0.05), while significant differences were found in the awareness rate of T. solium taeniasis and cysticercosis control knowledge among medical professionals in terms of education levels (χ2 = 8.190, P < 0.05) and duration of working experiences (χ2 = 12.617, P < 0.05), and the awareness rate of T. solium taeniasis and cysticercosis control knowledge increased with education levels among medical professionals (χ2 = 6.768, P < 0.05). Only 5.52% (9/163) of the medical professionals had a history of diagnosis and therapy of T. solium taeniasis or cysticercosis, and only 1.23% (2/163) received training on T. solium taeniasis and cysticercosis control knowledge during the past 5 years. Results from the 2020 questionnaire survey showed a higher awareness rate of T. solium taeniasis and cysticercosis control knowledge among medical professionals in the intervention group (93.55%, 116/124) than in the control group (46.60%, 48/103) (χ2 = 61.845, P < 0.05), and no significant differences were seen in the awareness rate of T. solium taeniasis and cysticercosis control knowledge among medical professionals in terms of gender, level of medical professionals, duration of working experiences or history of diagnosis/therapy of T. solium taeniasis and cysticercosis in the intervention group (χ2 = 1.089, 0.140, 0.081 and 0.453, all P values > 0.05), while there was a significant difference in the awareness rate among medical professionals with different education levels (χ2 = 36.338, P < 0.05). In addition, the awareness rate of T. solium taeniasis and cysticercosis control knowledge significantly increased among medical professionals with various chracteristics in 2020 than in 2016. Conclusions In the low-prevalence areas of T. solium taeniasis and cysticercosis, long-term and persistent training may improve the awareness of T. solium taeniasis and cysticercosis control knowledge among grassroots medical professionals, which facilitates the timely identification of T. solium taeniasis and cysticercosis and the establishment of a sensitive disease surveillance system.

Study on the mechanism of "guiding action" of borneol in Suxiaojiuxin pills / 药学学报

In order to research the mechanism of guiding action of borneol in Suxiaojiuxin pills, the model of in vitro intestinal absorption, in vivo drug metabolism of mice and cell in vitro absorption model of Caco-2 were established firstly. All animal experiments were in accordance with the regulations of the Animal Ethics Committee of Nankai University. The results showed that the cumulative absorption quantity and absorption permeability of ferulic acid and ligustilide in the intestinal juice of Suxiaojiuxin pills group were significantly increased comparing with fake Suxiaojiuxin pills group, which don't contain borneol. By using borneol, the content of ferulic acid and ligustilide in the blood and tissues, such as heart, were added. The transepithelial resistance value and the content of horseradish peroxidase (HRP) in Caco-2 were rapidly decreased and increased, respectively. Due to further explore mechanism of promoting intestinal absorption of borneol for drugs, in this study, photosensitive probes of borneol were synthesized to capture its targets, and dual luciferase reporter system was used to evaluate its activity of calcium. It was found that it could make calcium overload by regulating transient receptor potential cation channel, subfamily M, member 8 (TrpM8). Then, the results of mass spectrometry imaging showed that the accumulation of ferulic acid in the heart was significantly increased by borneol, and the relaxation rate of rat thoracic aorta was enhanced obviously. In summary, the borneol in Suxiaojiuxin pills can expand cell space and increase intestinal permeability by acting on TrpM8, thus promoting the intestinal absorption, tissue distribution and target organ enrichment of drugs.

Genomic Epidemiology of Imported Cases of COVID-19 in Guangdong Province, China, October 2020 - May 2021 / 生物医学与环境科学（英文）

Objective@#The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated.@*Methods@#In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants.@*Results@#We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations.@*Conclusion@#These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.

Single-copy Loss of Rho Guanine Nucleotide Exchange Factor 10 ( arhgef10) Causes Locomotor Abnormalities in Zebrafish Larvae / 生物医学与环境科学（英文）

OBJECTIVE@#To determine if ARHGEF10 has a haploinsufficient effect and provide evidence to evaluate the severity, if any, during prenatal consultation.@*METHODS@#Zebrafish was used as a model for generating mutant. The pattern of arhgef10 expression in the early stages of zebrafish development was observed using whole-mount in situ hybridization (WISH). CRISPR/Cas9 was applied to generate a zebrafish model with a single-copy or homozygous arhgef10 deletion. Activity and light/dark tests were performed in arhgef10 -/-, arhgef10 +/-, and wild-type zebrafish larvae. ARHGEF10 was knocked down using small interferon RNA (siRNA) in the SH-SY5Y cell line, and cell proliferation and apoptosis were determined using the CCK-8 assay and Annexin V/PI staining, respectively.@*RESULTS@#WISH showed that during zebrafish embryonic development arhgef10 was expressed in the midbrain and hindbrain at 36-72 h post-fertilization (hpf) and in the hemopoietic system at 36-48 hpf. The zebrafish larvae with single-copy and homozygous arhgef10 deletions had lower exercise capacity and poorer responses to environmental changes compared to wild-type zebrafish larvae. Moreover, arhgef10 -/- zebrafish had more severe symptoms than arhgef10 +/- zebrafish. Knockdown of ARHGEF10 in human neuroblastoma cells led to decreased cell proliferation and increased cell apoptosis.@*CONCLUSION@#Based on our findings, ARHGEF10 appeared to have a haploinsufficiency effect.

Effectiveness of health education interventions targeting taeniasis and cysticercosis among primary school students in disease-elimination pilot areas of Henan Province / 中国血吸虫病防治杂志

Objective To compare the changes of knowledge, attitude and practice (KAP) related to taeniasis and cysticercosis among primary school students before and after health education interventions in disease-elimination pilot areas of Henan Province, so as to evaluate the effectiveness of health education interventions. Methods A primary school was selected from each of Dushu, Bowang and Yangji townships, Fangcheng County, Henan Province from 2017 to 2019; then, 2 to 3 classes were randomly selected from grade 4 to 6 in each primary school, and finally, all students in these classes were enrolled as study subjects. A thematic health education lecture pertaining to taeniasis and cysticercosis was given once each year by means of “health education in class”. The KAP towards taeniasis and cysticercosis was investigated among primary school students using selffilled structured questionnaires, and the changes of awareness of taeniasis and cysticercosis control knowledge and percentage of healthy behaviors formation were compared in primary school students among years and following various frequencies of health education interventions. Results More than 10 thousand person-time primary school students received health education interventions during the period from 2017 to 2019, and a total of 1 223 person-time primary school students were investigated during the 3-year study period, including 633 person-time men and 590 person-time women and 88.55% of primary school students at ages of 10 to 12 years. The proportion of households raising pigs and using dry toiliets decreased from 5.30% (24/453) and 18.10% (82/453) in 2017 to 3.60% (13/361) and 11.08% (40/361) in 2019, respectively. The awareness rate of taeniasis and cysticercosis control knowledge increased significantly from 0.22% (1/453) in 2017 to 62.59% (256/409) in 2018 and 76.73% (277/361) in 2019 (χ2 = 567.60, P < 0.001), and the awareness rate was 85.25% (104/122) among primary school students attending the thematic special health education courses for successive three times. The awareness rates of taeniasis and cysticercosis control knowledge were 0.44% (1/225), 58.00% (116/200) and 71.63% (149/208) among male students and 0 (0/338), 66.99% (140/209) and 83.66% (128/153) among female students from 2017 to 2019, and there was a significant difference in the awareness of taeniasis and cysticercosis control knowledge between male and female students in 2019 (χ2 = 7.14, P = 0.01). On-site teaching by doctors was the students’ favorite way to receive health education interventions (70.07%, 857/1 223), followed by watching health education videos (58.63%, 717/1 223) and seeing parasite specimens (48.9%, 598/1 223). The proportion of students’ families who used cutting boards for raw and cooked food separately increased from 7.28% (33/453) in 2017 to 47.37% (171/361) in 2019, was 67.21% (82/122) among students attending the health education courses for successive three times. The proportion of students who frequently washed their hands before meals and after using toilet increased from 71.96% (324/453) in 2017 to 89.47% (319/361) in 2019 and was 95.90% (117/122) among students attending the health education courses for successive three times. In addition, the percentage of students washing hands frequently in families using dry toilets was significantly lower in those who did not use dry toilets (χ2 = 9.21, P = 0.002), and the proportion of students with a habit of eating raw or undercooked meat decreased significantly from 35.76% (162/453) in 2017 to 6.65% (24/361) in 2019 (χ2 = 69.11, P < 0.01). Conclusion The thematic health education activity of “health education in class” contributes greatly to the increase in the awareness of taeniasis and cysticercosis control knowledge and the rate of healthy behaviors formation among primary school students in diseaseelimination pilot areas of Henan Province.

Protective effect of ethyl acetate extract from Bidens bipinnata on hepatocyte damage induced by endoplasmic reticulum stress / 中国中药杂志

To explore the protective effect and mechanism of ethyl acetate extract from Bidens bipinnata on hepatocyte damage induced by endoplasmic reticulum stress. Tunicamycin was used to establish the damage model in L02 cells. Methyl thiazolyl tetrazolium(MTT) colorimetric assay was used to investigate the survival rate of ethyl acetate extract from B. bipinnata in L02 cells injury induced by endoplasmic reticulum stress; the protein expressions of endoplasmic reticulum stress-related molecule glucose regulated protein 78(GRP78), PKR-like ER kinase(PERK), eukaryotic initiation factor-2(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(CHOP), B-cell CLL/lymphoma 2(Bcl-2), Bal-2 associated X apoptosis regulator(Bax) were examined by Wes-tern blot. The expressions of the above proteins were also detected after endoplasmic reticulum stress inhibitor(4-phenyl butyric acid) and CHOP shRNA-mediated knockdowns were added. The expressions of GRP78, PERK, CHOP in L02 cells were observed by immunofluorescence method. The results showed that ethyl acetate extract from B. bipinnata could significantly increase the survival rate of L02 cell injury caused by endoplasmic reticulum stress in a dose and time-dependent manner(P<0.05 or P<0.01). The expression levels of GRP78, PERK, eIF2α, ATF4, CHOP and Bax in the drug treatment groups were significantly down-regulated(P<0.05 or P<0.01), while Bcl-2 was significantly up-regulated(P<0.01). After endoplasmic reticulum stress inhibitor and CHOP shRNA-mediated knockdowns were added, the expression levels of GRP78, PERK, eIF2α, ATF4, CHOP, Bax in the drug treatment groups were significantly down-regulated(P<0.01), whereas Bcl-2 was significantly up-regulated(P<0.01). Immunofluorescence results showed that the expressions of GRP78, PERK, CHOP were consistent with the Western blot method. In conclusion, ethyl acetate extract from B. bipinnata has a significant protective effect on the damage of L02 cells caused by endoplasmic reticulum stress. The mechanism may be related to the inhibition of endoplasmic reticulum stress and the down-regulation of apoptosis in cells through the PERK/eIF2α/ATF4/CHOP signaling pathway.

N-Glycans and intact glycopeptide-based characterization of N-glycosylation of monoclonal antibody drugs / 药学学报

In recent years, the biopharmaceutical industry has grown rapidly, and the market size of monoclonal antibody drugs has increased significantly. Accurate structural characterization and quality control are the supporting technologies for the development of monoclonal antibody drugs. As a significant post-translational modification of antibody drugs, glycosylation has an important influence on its efficacy, stability, and immunogenicity. The existing literature usually uses liquid chromatography-mass spectrometry to perform major glycosylation modifications of monoclonal antibody drugs. Characterization, there are few studies on low-abundance glycosylation, but the characterization and control of low-abundance glycosylation cannot be ignored. In this study, we have established a qualitative and quantitative analysis technology for N-glycans based on RapiFluor-MS reagent-labeled monoclonal antibody drugs. This method has a short sample processing time and high sensitivity. It can not only characterize the main glycoforms of three monoclonal antibody drugs (adalimumab, bevacizumab, and trastuzumab) but also can quantify low-abundance N-glycans. The results of the study showed that the main glycoforms specified in the Pharmacopoeia could be detected in different batches of monoclonal antibody drugs, but the content of N-glycans in different batches of samples is not identical. After that, we analyzed the N-glycans connection sites and glycoforms at the intact glycopeptide level, further enriching the N-glycans structure information of the monoclonal antibody. The qualitative and quantitative analysis technology of N-glycans based on RapiFluor-MS reagent-labeled monoclonal antibody drugs can realize the in-depth characterization and control of glycosylation modification of monoclonal antibody drugs.

The latest research progress on early diagnosis of lung cancer according to CT-based computer intelligent analysis / 中国胸心血管外科临床杂志

@#Lung cancer has brought tough challenges to human health due to its high incidence and mortality rate in the current practice. Nowadays, computed tomography (CT) imaging is still the most preferred diagnostic tool for early screening of lung cancer. However, a great challenge brought from accumulative CT imaging data can not meet the demand of the current clinical practice. As a novel kind of artificial intelligence technique aimed to deal with medical images, a computer-aided diagnosis has been found to provide useful auxiliary information, attenuate the workload of doctors, and significantly improve the efficiency and accuracy for clinical diagnosis of lung cancer. Therefore, an effective combination of computer-aided techniques and CT imaging has increasingly become an active area of investigation in early diagnosis of lung cancer. This review aims to summarize the latest progress on the diagnostic value of computer-aided technology with regard to early stage lung cancer from the perspectives of machine learning and deep learning.

Effect of staging treatment of / 中国针灸

OBJECTIVE@#To compare the effect of @*METHODS@#A total of 74 patients with RIF of thin endometrium type undergoing freeze-thaw embryo transfer were randomly divided into an observation group (37 cases) and a control group (37 cases). The patients in the control group were treated with freeze-thaw embryo transfer in hormone replacement cycle, and the estradiol valerate tablets were taken orally from the fifth day of menstruation, 2 mg per day. On the basis of the control group, the observation group was additionally treated with @*RESULTS@#The clinical pregnancy rate was 37.8% (14/37) in the observation group, which was higher than 16.2% (6/37) in the control group (@*CONCLUSION@#On the basis of conventional medication,

Systematic evaluation and trail sequential analysis of efficacy and safety of Yangxue Qingnao Granules in treatment of essential hypertension and its accompanying symptoms / 中国中药杂志

To systematically evaluate the efficacy and safety of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and its accompanying symptoms. PubMed, EMbase, Cochrane Library, VIP, CNKI, Wanfang, and China biomedical database(CBD) were searched to screen out from the establishment of the database to April 2020 about the clinical randomized controlled trials of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and accompanying symptoms. The articles were selected according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. TSA 0.9.5.10 Beta software was used for sequential analysis, and GRADE 3.6 was used for evidence quality evaluation. A total of 4 532 patients were included in 34 randomized controlled trials. Meta-analysis results showed that: Yangxue Qingnao Granules combined with conventional anti-hypertensive agents reduced systolic blood pressure(MD=-10.56, 95%CI[-13.63,-7.50], P<0.000 01) and diastolic blood pressure(MD=-8.21, 95%CI[-10.84,-5.59], P<0.000 01), improved total effective rate(RR=1.21, 95%CI[1.14, 1.29], P<0.000 01), improved patients dizziness(RR=1.29, 95%CI[1.21, 1.37], P<0.000 01), insomnia(RR=1.66, 95%CI[1.44, 1.91], P<0.000 01), headache(RR=1.32, 95%CI[1.21, 1.43], P<0.000 01), chest distress(RR=1.26, 95%CI[1.12, 1.42], P=0.000 1), memory loss(RR=1.24, 95%CI[1.10, 1.40], P=0.000 4), palpitation(RR=1.28, 95%CI[1.17, 1.41], P<0.000 01), and improved traditional Chinese medicine symptom scores(MD=-4.24, 95%CI[-5.25,-3.23], P<0.000 01) and headache symptom improvement scores(MD=-2.02, 95%CI[-2.51,-1.53], P<0.000 01) as compared with Western medicine group alone. Subgroup analysis results showed that Yang-xue Qingnao Granules combined with ACEI drug had more obvious effects in lowering systolic blood pressure and diastolic blood pressure. There was no statistically significant difference in the incidence of adverse reactions, and no abnormal liver and kidney function was observed in each study. Trial sequential analysis showed that the total effective rate was cumulative across the traditional and TSA thresholds, further confirming its clinical efficacy. The evidence level was mostly low or extremely low in GRADE evaluation. The clinical application of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and its accompanying symptoms is clear and safe, so it is recommended for clinical application.

Systematic evaluation and trial sequential analysis of Tianma Gouteng Granules combined with anti-hypertensive drugs in treatment of essential hypertension / 中国中药杂志

To systematically evaluate the efficacy and safety of Tianma Gouteng Granules combined with conventional anti-hypertensive drugs in the treatment of essential hypertension. The clinical randomized controlled trials(RCTs) on the treatment of essential hypertension with Tianma Gouteng Granules combined with conventional anti-hypertensive drugs were searched in PubMed, EMbase, Cochrane Library, VIP, CNKI, Wanfang, SinoMed since the establishment of the databases to April 2020 based on inclusion and exclusion criteria, and Meta-analysis was conducted by using RevMan 5.3 software. A total of 15 RCTs were included, involving a total of 1 508 patients. Meta-analysis results showed that Tianma Gouteng Granules combined with conventional Western medicine were supe-rior to the control group in reducing systolic blood pressure(MD=-10.24, 95%CI[-13.54,-6.95], P<0.000 01), diastolic blood pressure(MD=-5.33, 95%CI[-7.21,-3.45], P<0.000 01), improving the clinical efficacy of patients(RR=1.22, 95%CI[1.15, 1.28], P<0.000 01) and curative effect of traditional Chinese medicine syndrome(RR=1.26, 95%CI[1.02, 1.57], P=0.04), increasing nitric oxide content(MD=9.59, 95%CI[7.23, 11.96], P<0.000 01), reducing endothelin-1(MD=-10.74, 95%CI[-15.74,-5.75], P<0.000 1), tumor necrosis factor(MD=-0.28, 95%CI[-0.36,-0.19], P<0.000 01), and interleukin-6(MD=-39.71, 95%CI[-43.40,-36.03], P<0.000 01). There was no statistically significant difference between the test group and the control group in the incidence of adverse reactions. No liver and kidney dysfunction occurred. The results of the subgroup analysis showed that the effect of Tianma Gouteng Granules combined with ARB drugs was more obvious in reducing the systolic and diastolic pressure. Trial sequential analysis showed that the studies accumulatively included for clinical efficacy crossed the traditional threshold and the TSA threshold, further affirming its clinical efficacy. The clinical application of Tianma Gouteng Granules combined with conventional Western medicine in the treatment of primary hypertension and accompanying symptoms has clear efficacy and certain safety, so it is recommended for clinical application.