Relationship between self-reported occupational noise exposure and expression levels of plasma inflammatory cytokines in adult asthmatic patients / 公共卫生与预防医学

Objectives To investigate the relationship between self-reported occupational noise exposure and levels of plasma inflammatory cytokines in asthmatic patients. Methods A total of 910 adult asthmatic patients were selected as the study subjects, and their occupational noise exposure history and other related information were collected. The peripheral blood samples were collected from the patients, and the expression levels of plasma soluble CD14 (sCD14), complement factor D (CFD), Eotaxin-11 (CCL11), and IL-9 were determined. The relationship between self-reported occupational noise exposure and the expression levels of the four inflammatory cytokines in patients’ plasma were analyzed using multiple linear regression models. The interactions between confounding factors and self-reported occupational noise exposure were further analyzed by interaction analysis. Results The plasma CCL11, sCD14 and CFD expressions in asthmatic patients with self-reported occupational noise exposure were significantly higher than those in patients without the exposure (P<0.05). After adjusting for confounding factors, compared with patients reporting no occupational noise exposure, the plasma CFD expression was increased by 0.17 (95% CI: 0.02, 0.31) natural logarithm units in patients with self-reported occupational noise exposure. During remission, the levels of plasma CCL11 and sCD14 in asthmatic patients with self-reported occupational noise exposure were increased by 0.27 (95% CI: 0.05, 0.49) and 0.22 (95% CI: 0.02, 0.41) natural logarithm units, respectively, when compared with patients without the exposure. Interaction analysis showed that self-reported occupational noise exposure had significant multiplicative interaction with smoking or pet ownership on plasma CCL11 or CFD expressions in asthmatic patients (all P<0.05). Conclusion Self-reported occupational noise exposure is significantly associated with increased expression levels of plasma CFD, CCL11, and sCD14 in adult asthmatic patients.

Construction of a novel time-specific NLRP3 transgenic mouse model by Cre-LoxP system / 中国药理学通报

Aim To construct and identify a new time-specific NLRP3 point mutation transgenic mouse model by Cre-LoxP system. Methods Cre-LoxP system was used to generate NL-RP3

Investigation on the mechanism of anti-drug-induced liver injury and related effector substances of traditional Chinese medicine from the perspective of metabolism / 药学学报

Drug-induced liver injury (DILI) is one of the common clinical adverse drug reactions and remains a major cause of drug restriction, development termination and withdrawal from the pharmaceutical market today. In recent years, a variety of chemical components and metabolites of traditional Chinese medicine (TCM), as well as the endogenous effector substances influenced by metabolism of both, have attracted much attention for their significant hepatoprotective activities. However, the mechanism of TCM against DILI is complex, the related effector substances are still unclear, and its metabolism-related studies are still relatively weak. Therefore, this review summarized the mechanisms of DILI and its treatment by TCM from the perspective of metabolism, and for the first time, innovatively classified the Chinese medicine effector substances into two categories: exogenous (active components and metabolites of TCM) and endogenous (intestinal probiotics and endogenous metabolites), in order to reduce the occurrence of DILI, explore and develop effective anti-drug-induced liver injury effector substances of TCM, and further develop clinical drugs with hepatoprotective effects.

Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway / 中国中药杂志

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.

Mechanism of Mongolian drug Naru-3 in initiation of neuroinflammation of neuropathic pain from MMP9/IL-1β signaling pathway / 中国中药杂志

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.

Efficacy and safety of bevacizumab combined with capecitabine in the treatment of advanced breast cancer / 国际肿瘤学杂志

Objective:To investigate the efficacy and safety of bevacizumab combined with capecitabine in the treatment of advanced breast cancer.Methods:Seventy-six patients with advanced breast cancer who were diagnosed in the Cancer Center of the People's Liberation Army Navy Anqing Hospital from August 2019 to May 2021 were selected. According to different treatment schemes, the patients were divided into the control group (using single drug capecitabine) and the test group (using bevacizumab combined with capecitabine), with 38 cases in each group. After 4 cycles of treatment, the clinical efficacy, progression-free survival (PFS), overall survival (OS) and adverse reactions were compared between the two groups, and the levels of vascular endothelial growth factor (VEGF) -121, VEGF-145, VEGF-165 and quality of life before and after treatment were compared.Results:The objective remission rate of the test group [57.89% (22/38) ] was higher than that of the control group [42.11% (16/38) ], but there was no statistically significant difference ( χ2=1.89, P=0.169) ; The disease control rate of the test group [81.58% (31/38) ] was better than that of the control group [55.26% (21/38) ], there was a statistically significant difference ( χ2=6.09, P=0.014). The median PFS of patients in the test group (6.3 months) was longer than that in the control group (4.2 months), there was a statistically significant difference ( χ2=0.48, P=0.003) ; The median OS of patients in the test group (14.8 months) was not significantly different from that in the control group (13.2 months) ( χ2=0.15, P=0.704). After treatment, the expression level of serum VEGF-121 [ (201.25±18.37) ng/L vs. (276.83±20.26) ng/L], VEGF-145 [ (102.24±12.16) ng/L vs. (170.39±15.28) ng/L], VEGF-165 [ (135.08±14.32) ng/L vs. (210.53±16.09) ng/L] in the test group was lower than that in the control group, there were statistically significant differences ( t=17.03, P<0.001; t=21.51, P<0.001; t=21.59, P<0.001). After treatment, patients in the test group were assessed according to 36-item Short-Form (SF-36) physiological function [ (80.18±13.96) score vs. (71.72±16.12) score], physiological function [ (67.19±30.62) score vs. (53.12±9.86) score], physical pain [ (70.01±17.97) score vs. (61.06±17.57) score], overall health [ (68.67±18.92) score vs. (57.96±20.97) score], vitality [ (78.39±19.37) score vs. (68.26±18.52) score], social function [ (82.24±19.73) score vs. (70.92±20.31) score], the scores of emotional function [ (73.81±28.86) score vs. (60.23±29.19) score] and mental health [ (76.19±12.82) score vs. (70.31±12.54) score] were higher than those of the control group, there were statistically significant differences ( t=2.45, P=0.017; t=2.03, P=0.046; t=2.19, P=0.031; t=2.34, P=0.022; t=2.33, P=0.023; t=2.46, P=0.016; t=2.04, P=0.045; t=2.02, P=0.047). The incidence of adverse reactions in the test group [18.42% (7/38) ] was lower than that in the control group [76.32% (29/38) ], there was a statistically significant difference ( χ2=25.54, P<0.001) . Conclusion:The combination of bevacizumab and capecitabine chemotherapy has a higher clinical effect on advanced breast cancer, which can significantly reduce the level of VEGF in patients, improve the quality of life of patients, with mild adverse reactions and high safety.

Effect of surgical resection after preoperative immunotherapy combined chemotherapy on unresectable stage Ⅲ non-small cell lung cancer / 中华胸心血管外科杂志

Objective:Immune checkpoint inhibitors have a high remission rate in the preoperative application of resectable and potentially resectable non-small cell lung cancer when combined with chemotherapy. For the unresectable stage Ⅲ non-small cell lung cancer, whether the transformation can be achieved through this regimen to provide opportunities for surgical resection is controversial. In this study, we evaluated the pattern of transformation therapy by reviewing the efficacy and safety of preoperative therapy and surgery of this group.Methods:A review of 23 patients undergoing surgical resection after transformation therapy by preoperative immunotherapy combined chemotherapy between November 2019 and November 2021 was performed. All patients must clarify the pathological diagnosis of non-small cell lung cancer by biopsy. After the multi-disciplinary treatment team and preoperative imaging assessment, the diagnosis should be consistent with unresectable stage III as described in the Expert Consensus on Multidisciplinary Management of Stage Ⅲ Non-Small Cell Lung Cancer, 2019 Edition. After 2 to 4 cycles of preoperative anti-PD-1 monoclonal antibody combined with chemotherapy, the surgical team assessed the chance of resection and performed surgery. Important indicators such as surgical resection rate, R0 resection rate, MPR, pCR, incidence of grade 3-5 adverse reactions and various other perioperative data were counted.Results:In the whole group, initial imaging evaluation was 10 of stage cⅢA and 13 of stage cⅢB.15 cases had multiple stations N2 lymph nodes metastasis, 9 had enlarged fused N2 lymph nodes metastasis, 6 had large vessel invasion(T4), and 1 had contralateral mediastinal lymph node metastasis(N3). After preoperative neoadjuvant therapy, 17 cases achieved PR, 3 achieved SD and 3 achieved PD. The surgical resection rate of the whole group was 91.3%(21/23, 1 lobectomy combined with superior vena cava reconstruction, 2 sleeve lobectomy, 5 pneumonectomy, 12 lobectomy/combined lobectomy, 1 wedge resection and 2 unresectable cases), R0 resection rate was 95.2%(20/21). MPR was achieved in 13 cases, 8 of them reached pCR. There were no perioperative deaths, median surgical time was 260(190-460) min, median bleeding volume was 100(50-750) ml, median drainage time was 5(3-9) days, and median hospitalization was 7(5-11) days. Two cases got immunotherapy-related grade 3 adverse reactions, one was interstitial pneumonia and the other was immune-related injury involving the eye, oral and genital mucosa. Two cases got surgical complications and one was persistent lung leakage, which stopped after 46 days of conservative treatment; The other was pleural effusion, which was relieved after drainage.Conclusion:For the unresectable stage Ⅲ NSCLC, immunotherapy combined chemotherapy is an effective preoperative downstage method. It can convert 91.3% cases to resectable ones while achieving a good degree of pathological remission. Its side reactions are generally controllable and safety.

Effects of puerarin on blood pressure and aortic endothelial function in obese mice / 中国药理学通报

Aim To explore the effeet of puerarin (Pue) on aortic function and blood pressure in hyper-tensive mice induced by high-fat diet.Methods Thirty male mice were divided into five groups named as normal diet group ( Con ) , high-fat diet group (1)10), high-fat diet + low-dose puerarin group (20 mg 'kg-1 •(!"'), high-fat diet + medium-dose puera¬rin (40 mg • kg"1 • d ~1 ) group and high-fat diet + high-dose puerarin group (80 mg 'kg-1 • d~l).Hie mice were injected intraperitoneally with Pue for eight weeks.Body weight, blood pressure and blood glucose were measured.Serum was collected to detect blood lipid.Aortas were separated from aortic endothelial cells to test the vasodilative function.Aortic endotheli¬al cells from 1)10 mice were isolated to perform Iran-swell and cell proliferation experiments.Results I High-rlose puerarin treatment could reduce the body weight, body fat, blood glucose and blood pressure in obese mice ( P < 0.01 ) ; 2 High dose of puerarin could improve the vasodilative function of aortas com¬pared with those from 1)10 mice (P <0.01 ) ; (3) The migration ability of primary endothelial cells from 1)10 + Pue group was improved compared with that from 1)10 group (P <0.01 ).Conclusions Puerarin can significantly reduce blood pressure in obese mice in¬duced by high fat diet by improving the aortic diastolic function and endothelial cell proliferation and migra-tion.

Clinical observation on filiform-fire needling of "Biaoben acupoint combination" for 33 cases of sequelae of coronavirus disease 2019 during recovery period / 中国针灸

OBJECTIVE@#To observe the clinical therapeutic effect of filiform-fire needling of "Biaoben acupoint combination" on the sequelae of patients with coronavirus disease 2019 (COVID-19) during the recovery period.@*METHODS@#A total of 33 patients with COVID-19 during the recovery period were treated with filiform-fire needling at the acupoints of Mingmen (GV 4), Shenzhu (GV 12), Gaohuang (BL 43), Zusanli (ST 36) and Shangjuxu (ST 37), etc., once every other day, 3 times a week, and 3 times was one course of treatment and totally 2 courses of treatment were required. The TCM symptom, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores, pulmonary function indexes (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], peak expiratory flow [PEF]) and chest CT imaging change were observed before and after treatment, and the therapeutic effect was evaluated.@*RESULTS@#After treatment, the scores of TCM symptom, HAMA and HAMD were decreased compared with those before treatment (P<0.05), and the levels of FVC, FEV1 and PEF were increased compared with those before treatment (P<0.05), and the recovery rate of 22 patients with pulmonary ventilation dysfunction was 86.4% (19/22). After treatment, the lung shadow area was smaller than that before treatment (P<0.05). The effective rate of 25 patients with lung CT abnormalities was 84.0% (21/25). After treatment, 23 cases were cured, 5 cases were markedly effective, 4 cases were effective, 1 case was ineffective, the cured and markedly effective rate was 84.8%.@*CONCLUSION@#The filiform-fire needling of "Biaoben acupoint combination" could significantly reduce the sequelae of cough, fatigue, chest tightness, etc. and mental symptoms such as anxiety and depression in patients with COVID-19 during the recovery period, and promote inflammatory exudation absorption of pulmonary lesion and improve lung ventilation function.

A new ent-kauranoid from rhizomes of Canna generalis / 药学学报

Two ent-kauranoids were isolated from the ethanol extraction of rhizomes of Canna generalis (Cannaceae), and were purified by various technologies, including silica gel and high performance liquid chromatography, and their structures were determined by modern spectroscopy techniques as (5R,8S,9S,10R,13R)-2-oxo-ent-kaur-15-en-17-oic acid (1) and (4R,5S,8S,9S,10S,13R)-19-hydroxy-ent-kaur-15-en-17-oic acid (2). Compound 1 is a new ent-kauranoid, and compound 2 is obtained from rhizomes of Canna generalis for the first time.

Clinicopathological features and prognosis of high-grade B-cell lymphoma with MYC and bcl-2 and/or bcl-6 rearrangements / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma β2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements (P<0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement (P<0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements (P>0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.

Application effect of MOOC+CBL teaching mode in practice teaching of nuclear medicine SPECT/CT / 中华医学教育探索杂志

Objective:To explore the application effect of massive online open course (MOOC) + case-based learning (CBL) in SPECT/CT practice teaching of nuclear medicine.Methods:Twenty-nine interns of nuclear medicine SPECT/CT in Xiaogan Hospital Affiliated to Wuhan University of Science and Technology from January 2020 to October 2020 were selected as the research group and received MOOC + CBL teaching. Taking 31 interns from January 2019 to October 2019 as the control group, and the traditional teaching method was conducted. At the end of the internship, the students' theoretical and operational skills were assessed. Their learning motivation and thinking ability were evaluated by using the study process questionnaire (SPQ) and the Chinese version of California critical thinking disposition inventory (CTDI-CV), and the two groups' satisfaction with teaching was compared. SPSS 22.0 was used for Chi-square test and t-test. Results:The results of theoretical knowledge, PET/CT case analysis and image diagnosis in the study group were higher than those in the control group ( P<0.05). The total scores of surface motivation, deep motivation and SPQ in the study group were higher than those in the control group ( P<0.05). The self-confidence scores of open mind, analytical ability, systematization ability, and critical thinking and CTDI-CV total scores of the study group were higher than those of the control group ( P<0.05). The study group was more satisfied with the teaching and the enhancement of self-study ability than the control group ( P<0.05). Conclusion:MOOC + CBL teaching for nuclear medicine SPECT/CT interns can improve their examination results, learning motivation and thinking ability, and also enhance their self-study ability.

The auxiliary diagnostic value of combined detection of serum midkine and thyroid stimulating hormone for differentiated thyroid cancer / 中国医师进修杂志

Objective:To investigate the auxiliary diagnostic value of serum midkine (MK) and thyroid stimulating hormone (TSH) for differentiated thyroid cancer (DTC).Methods:Seventy-one postoperative DTC patients (DTC group) treated with 131I were selected, and 143 patients with benign thyroid lesions (benign thyroid disease group) treated with surgery in Center Hospital of Xiaogan from March 2019 to December 2020 at the same period were also selected. Clinical data such as liver and kidney function indexes, positive rate of anti thyroglobulin antibodies (TGAb) and positive rate of thyroid peroxidase antibody (TPOAb) were collected before treatment, and their fasting blood samples were collected before treatment. Fully automated electrochemiluminescence immunoassay was used to measure free thyroxine (FT 4), free triiodothyronine (FT 3), TSH levels in patients′ serum. The serum MK levels were measured by enzyme-linked immunosorbent assay (ELISA). Binary Logistic regression model was used to screen for independent risk factors for the development of DTC. A receiver operating characteristic curve (ROC) was drawn to evaluate the efficacy of MK, TSH and MK combined with TSH, in aiding the diagnosis of DTC and its staging. Results:Serum TSH and MK levels in DTC group were higher than those in benign thyroid disease group: (3.55 ± 0.61) mU/L vs. (2.97 ± 0.46) mU/L, (394.25 ± 63.36) ng/L vs. (311.45 ± 42.66) ng/L, and the differences were statistically significant ( P<0.05). Elevated serum TSH and MK levels were independent risk factors for DTC. When MK combined with TSH was used to diagnose DTC, the area under the curve (AUC), sensitivity and specificity were higher than those of MK and TSH alone (0.925 vs. 0.859 and 0.783, 83.10% vs. 78.87% and 73.24%, 89.51% vs. 85.31% and 79.02%), and the differences were statistically significant ( P<0.05). Serum TSH and MK levels in stage Ⅲ and Ⅳ patients in DTC group were higher than those in stage Ⅰ and Ⅱ patients: (3.79 ± 0.65) mU/L vs. (3.42 ± 0.56) mU/L, (427.88 ± 52.73) ng/L vs. (311.45 ± 42.66) ng/L, and the differences were statistically significant ( P<0.05). The AUC, sensitivity and specificity of MK combined with TSH in the diagnosis of different stages of DTC were higher than those of MK and TSH alone (0.822 vs. 0.657 and 0.666, 73.90% vs. 56.52% and 56.52%, 83.33% vs. 77.08% and 79.17%), and the differences were statistically significant ( P<0.05). Conclusions:Serum TSH and MK levels are independent risk factors for the occurrence of DTC in patients, and the combination of them has certain auxiliary diagnostic value for the identification and staging of DTC.

Mechanism of Anti-tuberculosis Particles （Kanglao Granule） Based on Network Pharmacology and Experimental Research / 中国实验方剂学杂志

ObjectiveTo explore the potential anti-tuberculosis mechanism of Kanglao granule through network pharmacology. MethodThe active components of Kanglao granule were retrieved from related databases and the potential targets of the components from SwissTargetPrediction. Targets of the tuberculosis were screened from GeneCards and National Center for Biotechnology Information （NCBI）， and the anti-tuberculosis targets of the prescription were further identified. STRING and Cytoscape 3.8.0 were employed to construct the Chinese medicinal-disease target-signaling pathway network and screen core targets. Then gene ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed. Finally， AutoDock Vina was used for molecular docking between the active components of the prescription and key proteins and Western blotting for verifying the interaction between them. ResultA total of 29 important chemical components in the prescription were screened out， including β-sitosterol， sesamin， and kaempferol. A total of 28 key anti-tuberculosis targets were retrieved， such as protein kinase B1 （Akt1）， epidermal growth factor receptor （EGFR）， hypoxia inducible factor-1A （HIF-1A）， proto-oncogene tyrosine-protein kinase （SRC）， and matrix metalloproteinase-9 （MMP-9）. Bioinformatics analysis showed the 28 targets were involved in 41 GO terms such as oxygen metabolism， nucleic acid transcription， and metabolic enzyme pathway， and 28 key KEGG pathways， including Mycobacterium tuberculosis signaling pathway and phosphatidylinositol 3 kinase/protein kinase B pathway. Molecular docking results showed that Akt1 had the strongest binding affinity to sesamin. In vitro experiment indicated that sesamin inhibited the growth of M. tuberculosis by suppressing the phosphorylation of Akt1. ConclusionKanglao granule improved the sterilization level and immune response through multi-component， multi-target， and multi-pathway interactions， thereby achieving therapeutic effect on tuberculosis. Akt1 is one of the important targets involved in the treatment of tuberculosis.

Clinical Efficacy of Modified Sanxiaoyin in Treatment of Mild or Moderate COVID-19 Patients： Based on Retrospective Analysis / 中国实验方剂学杂志

ObjectiveTo retrospectively analyze the clinical data of 52 patients with coronavirus disease-2019 （COVID-19） and explore the clinical efficacy of modified Sanxiaoyin on mild/moderate COVID-19 patients. MethodThe propensity score matching method was used to collect the clinical data of mild or moderate COVID-19 patients enrolled in the designated hospital of the Second Hospital of Jingzhou from December 2019 to May 2020. A total of 26 eligible patients who were treated with modified Sanxiaoyin were included in the observation group， and the 26 patients treated with conventional method were the regarded as the control. The disappearance of clinical symptoms， disappearance time of main symptoms， efficacy on traditional Chinese medicine （TCM） symptoms， hospitalization duration， laboratory test indicators， and CT imaging changes in the two groups were compared. ResultThe general data in the two groups were insignificantly different and thus they were comparable. After 7 days of treatment， the disappearance rate of fever， cough， fatigue， dry throat， anorexia， poor mental state， and poor sleep quality in the observation group was higher than that in the control group （P<0.05）， and the difference in the disappearance rate of expectoration and chest distress was insignificant. For the cases with the disappearance of symptoms， the main symptoms （fever， cough， fatigue， dry throat， anorexia， chest distress） disappeared earlier in the observation group than in the control group （P<0.01）. After 7 days of treatment， the scores of the TCM symptom scale of both groups decreased （P<0.01）， and the decrease of the observation group was larger that of the control group （P<0.01）. All patients in the two groups were cured and discharged. The average hospitalization duration in the observation group ［（12.79±2.68） d］ was shorter than that in the control group ［（15.27±3.11） d］ （P<0.01）. The effective rate in the observation group （92.31%， 24/26） was higher than that in the control group （76.92%， 20/26） . After 7 days of treatment， the lymphocyte （LYM） count increased （P<0.05）， and white blood cell （WBC） count and neutrophil （NEUT） count decreased insignificantly in the two groups. Moreover， levels of C-reactive protein （CRP）， erythrocyte sedimentation rate （ESR）， and procalcitonin （PCT） reduced in the two groups after treatment （P<0.01） and the reduction in the observation group was larger than that in the control group （P<0.01）. Through 7 days of treatment， the total effective rate on pulmonary shadow in the observation group （90.00%， 18/20） was higher than that in the control group （77.27%， 17/22） （P>0.05） and the improvement of lung shadow in the observation group was better than that in the control group （P<0.01）. ConclusionModified Sanxiaoyin can significantly alleviate fever， cough， fatigue， anorexia， chest distress， poor sleep quality， and other symptoms of patients with mild or moderate COVID-19， improve biochemical indicators， and promote the recovery of lung function. This paper provides clinical evidence for the application of modified Sanxiaoyin in the treatment of mild or moderate COVID-19.

Characteristics of pelvic floor structure and electrophysiology of pelvic floor muscle in female patients with stroke / 中国康复理论与实践

ObjectiveTo investigate the characteristics of pelvic floor structure and electrophysiology in female patients with stroke. MethodsFrom June to December, 2020, 21 female inpatients with stroke in Zhongda Hospital, Southeast University (stroke group) were divided into urinary incontinence (UI) group (n = 6) and non-urinary incontinence (NUI) group (n = 15), and other 20 healthy subjects were as control group. They were observed with pelvic floor ultrasonography and pelvic floor surface electromyogram. ResultsAverage electromyography, integral electromyography, root mean square, mean power frequency and median frequency decreased in UI and NUI groups compared with those of the control group (P < 0.05), but there was no significant difference between UI group and NUI group (P > 0.05). Bladder neck position, bladder neck angle, bladder neck mobility, urethral rotation angle; and anteroposterior diameter, left-right diameter and area of levator ani muscle hiatus after Valsalva's action were all not different among three groups (F < 2.484, P > 0.05). ConclusionThe activities of pelvic floor muscles decrease in female patients with stroke, without obvious changes of pelvic floor supporting structures, whatever UI.

Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1 / 国际口腔科学杂志·英文版

Osteoarthritis (OA) is a prevalent joint disease with no effective treatment strategies. Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis. Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies, the epigenetic control of OA remains unclear. Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes, including cell differentiation, proliferation, autophagy, and apoptosis. However, the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown. In this work, we confirmed the upregulation of JMJD3 in aberrant force-induced cartilage injury in vitro and in vivo. Functionally, inhibition of JMJD3 by its inhibitor, GSK-J4, or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury. Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression. Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis, cartilage degeneration, extracellular matrix degradation, and inflammatory responses. In vivo, anterior cruciate ligament transection (ACLT) was performed to construct an OA model, and the therapeutic effect of GSK-J4 was validated. More importantly, we adopted a peptide-siRNA nanoplatform to deliver si-JMJD3 into articular cartilage, and the severity of joint degeneration was remarkably mitigated. Taken together, our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression. Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-siRNA nanocomplexes.

Role of dexamethasone/captopril co-loaded immunoliposome-nanoparticle hybrids on the regulation of macrophage polarization in mice with glomerulonephritis / 药学学报

In this study, dexamethasone (DXMS) and captopril (CAP) were co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a surface coating of a phospholipid bilayer, and then the core-shell nanoparticles were modified with polyethylene glycol and integrin α8 antibody to obtain immunoliposome-nanoparticle hybrids (DXMS/CAP@PLGA-ILs). The role of nanoparticles on the renal targeting, anti-inflammatory effects, and macrophage differentiation were investigated. The results showed that the particle size of the nanoparticles was 115.9 ± 2.89 nm, and the core-shell structure could be observed under an electron microscope. The drug loading capacity of DXMS and CAP was 5.72% ± 0.37% and 7.51% ± 0.07%, respectively. The results of in vitro experiments showed that DXMS/CAP@PLGA-ILs could reduce the secretion of specific cytokines and the mRNA expression of markers in M2-type macrophages, thus promoting the differentiation of M2-type macrophages in the direction of unpolarized macrophages. In vivo experiments in mice showed that DXMS/CAP@PLGA-ILs had a significant renal targeting effect, which could restore the renal index, serum creatinine, and urea nitrogen levels of mesangial proliferative glomerulonephritis in mice. Moreover, DXMS/CAP@PLGA-ILs could reduce both the secretion of inflammatory cytokines and the mRNA expression levels of M1 and M2 macrophage markers in the kidney. All the animal experiments were in accordance with the regulations of Animal Ethics Committee of Sichuan Agricultural University. In conclusion, renal-targeting DXMS/CAP@PLGA-ILs could effectively regulate the polarization of macrophages and had an "anti-inflammatory/anti-fibrosis" therapeutic effect, providing a new strategy and basis for the targeted therapy of glomerulonephritis.

Research progress of the mechanism for PD-1 molecule regulating pulmonary fibrosis and its research prospects in silicosis / 公共卫生与预防医学

Programmed death factor-1 (PD-1) is a promising target molecule for clinical tumor immunotherapy in recent years. Recent studies suggest that PD-1 and related signaling pathways (PI3K/AKT, JAK/STAT3, p38MAPK, ERK, etc.) played a key regulatory role in the process of pulmonary fibrosis. Silicosis is a systemic disease caused by inhalation of free silicon dioxide dust, which is mainly characterized by extensive pulmonary nodular fibrosis and seriously endangers the health of patients. Dissecting the role of PD-1 in the pathogenesis of silicosis may be of great significance in the mechanism research and clinical diagnosis and treatment of silicosis. This paper reviews the regulation of PD-1 molecule on related signaling pathways and its role in pulmonary fibrosis, and looks forward to the potential application of these mechanistic studies in silicosis research.

Simultaneous determination of content of eight components in Caesalpinia decapetala by UPLC-MS/MS / 中国中药杂志

The present study established the ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of the content of eight major active components in Caesalpinia decapetala and performed the quality evaluation of C. decapetala from different habitats with the chemical pattern recognition. The analysis was carried out on a Waters BEH C_(18) column(2.1 mm×100 mm, 1.7 μm) at 40 ℃, with the mobile phase of water containing 0.1% formic acid(A) and acetonitrile containing 0.1% formic acid under gradient elution, the flow rate of 0.3 mL·min~(-1), and the injection volume of 1 μL. The electrospray ionization(ESI) source in the negative mode and multiple reaction monitoring(MRM) were used for MS quantitative analysis. The content results were analyzed by the hierarchical cluster analysis(HCA) and principal component analysis(PCA) for the evaluation of the quality difference. Eight components showed good linear relationships within their respective concentration ranges(r>0.999), with the average recoveries of 96.85%-103.4% and RSD of 0.52%-2.8%. The analysis results showed that the quality of samples from different batches was different. The samples were classified into three clusters by HCA and PCA. The method is simple, sensitive, accurate, and efficient, and can be used for the quality evaluation of C. decapetala.