Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota / 中国中药杂志

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Evidence mapping analysis of traditional Chinese medicine intervention in pulmonary fibrosis / 中国中药杂志

This study utilized evidence mapping methodology to systematically identify, describe, and evaluate the evidence from relevant research on traditional Chinese medicine(TCM) interventions in patients with pulmonary fibrosis. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched from database inception to March 2023 for systematic reviews/Meta-analysis/network Meta-analysis on TCM interventions in pulmonary fibrosis. The quality of included studies was assessed using the AMSTAR 2 scale, and the evidence mapping approach was employed to present comprehensive information on populations, intervention methods, the sample size in systematic reviews/Meta-analysis, and conclusion classifications. Ultimately, 44 systematic reviews/Meta-analysis/network Meta-analysis were included. Apart from syndrome differentiation and treatment, TCM injections accounted for a significant proportion of the observed interventions. The treatment methods were mainly focused on nourishing Qi and Yin, promoting blood circulation, resolving stasis, and dredging collaterals. The results from the included studies demonstrated that TCM treatment for pulmonary fibrosis could improve efficacy, increase lung function, improve PaO_(2 )levels, increase the 6-minute walk distance(6MWD), alleviate clinical symptoms, and enhance patients' quality of life. Based on the assessment using the AMSTAR 2 scale, methodological issues were identified, including the lack of protocol registration, failure to provide a list of excluded literature, and incomplete explanations regarding the impact of heterogeneity and bias on the results. The evidence mapping revealed that 42 conclusions were beneficial, while two conclusions were potentially beneficial. Overall, the quality of evidence was relatively low, primarily due to methodological imprecision and publication bias. Although TCM showed certain efficacy in the treatment of pulmonary fibrosis, the quality of reported literature, methodological quality, and overall evidence quality need improvement. It is recommended to conduct high-quality and standardized studies in the future to provide better evidence-based guidance.

Active fractions of Camellia nitidissima inhibit non-small cell lung cancer via suppressing epidermal growth factor receptor / 中国中药杂志

The present study explored the effects and its underlying mechanisms of four active fractions of Camellia nitidissima(leaf polyphenols, leaf saponins, flower polyphenols, and flower saponins in C. nitidissima) in inhibiting the proliferation and migration of non-small cell lung cancer(NSCLC) by suppressing the epidermal growth factor receptor(EGFR). MTT assay was used to detect the effect of four active fractions on the proliferation of NCI-H1975 and HCC827 cells. Wound healing assay and Transwell assay were adopted to evaluate the effect of four active fractions on the migration of NSCLC. The effect of four active fractions on the enzyme activity of EGFR was detected. Molecular docking was carried out to explore the direct action capacity and action sites between representative components of the four active fractions and EGPR. Western blot assay was employed to investigate the effect of four active fractions on the protein expression in EGFR downstream signaling pathways. The results of the MTT assay indicated that the cell viability of NCI-H1975 and HCC827 cells was significantly inhibited by four active fractions at 50, 100, 150, and 200 μg·mL~(-1) in a dose-dependent manner. Wound healing assay and Transwell assay revealed that the migration of NCI-H1975 and HCC827 cells was significantly suppressed by four active fractions. In addition, the results of the protein activity assay showed that the enzyme activity of EGFR was significantly inhibited by four active fractions. The molecular docking results confirmed that various components in four active fractions possessed strong binding activity to EGFR enzymes. Western blot assay revealed that four active fractions down-regulated the protein expression of EGFR and its downstream signaling pathways. It is concluded that the four active fractions of C. nitidissima can inhibit NSCLC. The mechanism may be related to EGFR and its downstream signaling pathways. This study provides a new scientific basis for the clinical treatment of NSCLC with active fractions of C. nitidissima, which is of reference significance for further research on the anti-tumor mechanism of C. nitidissima.

Analysis of Clinical Features and Prognosis of Patients with Chronic Neutrophil Leukemia / 中国实验血液学杂志

OBJECTIVE@#To provide clinical basis for the diagnosis and treatment of chronic neutrophilic leukemia (CNL) and to provide possible molecular targets for the treatment.@*METHODS@#By summarizing the clinical data of 14 patients with CNL, the clinical characteristics, gene mutation types and possible prognostic factors were analyzed.@*RESULTS@#Among the 14 patients with CNL, males (9 cases) were more than females (5 cases), with a median age of 57 years old. The detection rate of CSF3R mutation was 92.86% (13/14), including 12 cases (85.71%) with T318I mutation and 1 case of Y799X mutation, and only 1 case was not detected for mutation of CSF3R. The ASXL1 mutation was detected in 42.86% (6/14) of the patients, all of which were nonsense mutations, including 4 cases with R693X and 2 cases with E705X, and 14.29% (2/14) of the patients was detected for SETBP1 mutation, all of which were with D868N mutation. No patients with simultaneous ASXL1 and SETBP1 mutations were found, and JAK2 and CALR mutations were not detected. All of the patients had normal karyotypes. These patients' median survival time was 30 months (95%CI 13.19-46.80), and the influence of age over 60 years old was statistically significant (21.83 months vs 35.35 months) (P＜0.05).@*CONCLUSION@#It is difficult to diagnose CNL. CSF3R T618I mutation is its specific mutation, and ASXL1 mutation and SETBP1 mutation have auxiliary diagnostic significance for CNL. The age＞60 years old at diagnosis is a factor of unfavourable prognosis.

Advance in Exercise Rehabilitation for Nonspecific Low Back Pain (review) / 中国康复理论与实践

Nonspecific low back pain is a major contributor to disease burden worldwide and may affect people of all ages. As a key strategy in the management of low back pain, exercise rehabilitation has been unanimously recommended by several clinical practice guidelines. However, the guidelines didn't make it clear that the most optimum types, intensity, frequency and duration of exercise rehabilitation for patients with nonspecific low back pain. In the future, researchers should highlight the design of the exercise program, identify the patient subsets benefiting from specific exercise programs, exploit and popularize more effective and cost-effective exercise programs and promote active exercise in the patients with nonspecific low back pain to achieve complete rehabilitation.

Clinical Analysis of 208 Patiets with BCR/ABL Negative Myeloproliferative Neoplasms / 中国实验血液学杂志

OBJECTIVE@#To analyze the incidence, hemogram, genetics, clinical manifestations, therapeutic efficacy and outcome of patients with myeloproliferative neoplasms(MPN) so as to provide much more therapeutic basis for clinically studying the pathogenesis, diagnosis, and treatment as well as evaluating the prognosis of MPN patients.@*METHODS@#The clinical data and related laboratory test results in 208 cases of BCR/ABL fusion gene regative MPN were collected and analyzed retrospectively.@*RESULTS@#The MPN could occur at any age, but the highest incidence was observed in patients aged 40-79. Among 208 patients with MPN, the patients with essential thrombocythemia(ET) accounted for 48.56%(101/208), the patients with polycythemia vera(PV) accounted for 25.96%(54/208), and the patients with primary myelofibrosis(PMF) accounted for 25.48(53/208). The clinical manifestation of MPN varied, the first manifestations was no-specific, onset of disease presented slow. The JAK2V617F gene mutation existed in 130 out of 208 patients with MPN, total mutation rate was 62.5%;JAK2V617F mutation rate in PV patients was 81.5%(44/54), while that in ET and PMF patients was 58.4%(59/101) and 50.9%(27/53) respectively, the detected rate of this mutation in PV patients was significantly higher than that in ET and PMF patients (P0.05). In PV group, the WBC count of JAK2V617F positive patients was significantly enhanced (P0.05); in ET and PMF groups, the JAK2V617F positive patients had a higher WBC count and hemoglobin level(P0.05). The most common vascular event in patients with MPN was ischemic cerebrovascular disease. The JAK2V617F mutation related with risk of thrombosis (OR=2.222, 95% CI=1.101 to 4.486). The difference in the incidence of vascular event between ET and PV patients was no statistically significant (P>0.05), but the incidence of vascular event in ET and PV patients was higher than that in PMF patients(P<0.05). The disease conversion much more easily happened in JAK2V617F positive patients. After treatment, the MPN could be controlled, yet the maintained treatment is needed.@*CONCLUSION@#The MPN can occur almost at any age, but more commonly occures in middle-aged and elderly persons. The onset of MPN varies, the clinical manifestation was similar, a high detected rate of JAK2V617F mutation is observed in MPN patients and relates closely with onset of MPN; moreover, JAK2V617F mutation rate relates with type of MPN. The MPN patients with JAK2V617F mutation have higher WBC count and higher incidence of thrombosis. After treatment, the MPN can be better controlled, and need maintenance treatment. So as to avoid the reccurence of disease, control the complications and obtain the longterm survival.

Effect of Montelukast on T-lymphocyte subsets and advanced oxidation protein products in immune thrombopenic purpura model mice / 中国免疫学杂志

Objective:To investigate the effect of Montelukast on T-lymphocyte subsets, cytokines and advanced oxidation protein products ( AOPP ) in immune thrombopenic purpura ( ITP ) model mice. To analyze the principle of the treatment by Montelukast. Methods: Forty ITP mice were randomly divided into control group,model group,Montelukast low dose group(3 mg/kg) and Montelukast high dose group(12 mg/kg). ITP model mice were successive administration for 14 days after building models for 7 days. Platelet counts,the index of thymus and spleen were calculated. T-lymphocyte subsets were detected by flow cytometry. IL-6,TNF-α,AOPP were detected by enzyme linked immunosorbent assays. Results: Comparison with control group,the PLT,thymus index and spleen index,CD8+,IL-6,TNF-α,AOPP of model group mice were significantly increased (P＜0. 05) while CD3+,CD4+,CD4+/CD8+were significantly decreased (P＜0. 05). Comparison with model group,PLT,thymus index and spleen index,CD8+,IL-6,TNF-α,AOPP of low dose group and high douse group mice were significantly decreased (P＜0. 05) while CD3+,CD4+,CD4+/CD8+were significantly increased (P＜0. 05). Conclusion: Montelukast can cure ITP regulate immune disorders,eliminate accumulation of AOPP and reduce level of IL-6 and TNF-α.

Jiangtang Xiaozhi Recipe () prevents diabetic retinopathy in streptozotocin-induced diabetic rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe (, JXR) in streptozotocin (STZ)-induced diabetic rats.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into normal control group and diabetic group. Rats in the diabetic group were induced by intraperitoneal administration of STZ (50 mg/kg), and subdivided into 5 groups. Rats in the diabetic control group were given saline; four treatment groups were given metformin (300 mg/kg), JXR (2, 4 and 8 g/kg) respectively for 8 weeks, while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle. Body weight and food intake were measured every week. The hypoglycaemic effects were determined by testing fasting blood glucose (FBG) every other week, and hemoglobin A1c (HbA1c), insulin, and glucagon at the end of the treatment. The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining, and periodic acid-schiff staining. The effects were further evaluated by serum superoxide dismutase (SOD) activity and malondialdehyde (MDA).</p><p><b>RESULTS</b>High-dose JXR significantly reduced FBG and HbA1c level at the 8th week of administration (P<0.01, P<0.05). JXR significantly increased insulin level (P<0.05), and decreased glucagon level (P<0.05). JXR showed the antioxidant defense with increased SOD activity and decreased MDA contents in diabetic rats. Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups. Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment.</p><p><b>CONCLUSION</b>JXR have protective effect of diabetic retinopathy and its mechanism may be associated with the obvious hypoglycemic and antioxidant effect.</p>

IL-11 promotes the treatment efficacy of hematopoietic stem cell transplant therapy in aplastic anemia model mice through a NF-κB/microRNA-204/thrombopoietin regulatory axis

Hematopoietic stem cell (HSC) transplantation could be of therapeutic value for aplastic anemia (AA) patients, and immunosuppressants may facilitate the efficiency of the procedure. As anti-inflammatory cytokine interleukin-11 (IL-11) has a thrombopoietic effect, its use in cases of chronic bone marrow failure, such as AA, has been proposed to induce HSC function. However, the putative mechanisms that may support this process remain poorly defined. We found that decreased miR-204-5p levels were coincident with increased proliferation in mouse HSCs following exposure to IL-11 in vitro. Through inhibiting NF-кB activity, miR-204-5p repression was demonstrated to be a downstream effect of IL-11 signaling. miR-204-5p was shown to directly target thrombopoietin (TPO) via sequence-dependent 3′-UTR repression, indicating that this microRNA-dependent pathway could serve an essential role in supporting IL-11 functions in HSCs. Increased TPO expression in HSCs following IL-11 exposure could be mimicked or blocked by inhibiting or overexpressing miR-204-5p, respectively. Consistent with these in vitro findings, IL-11 promoted HSC engraftment in a mouse model of AA, an effect that was attenuated in cells overexpressing miR-204-5p. The reduction in miR-204-5p levels is an integral component of IL-11 signaling that may play an essential role in treating AA.

An analysis on the present situation of post setting in CDCs of Zhejiang Province / 预防医学

Objective To analyze the present post setting situation of CDCs in Zhejiang Province, and to provide evidence for further improvement and standardization of post setting. Methods The data of post setting were collected by questionnaires from all levels of CDCs in Zhejiang Province. The compliance and rationality of post setting structure were evaluated by national and provincial normative policy documents. Results Ninety seven CDCs had implemented the post setting. Professional technical posts had the highest proportion (above 80%) among three kinds of posts. As the approved proportions of posts classification and professional titles were approved by the local government, there were differences between different levels of CDCs. The approved proportion of ground skilled posts and management posts between municipal and county CDCs had a relatively higher degree of dispersion, and the CVs of ground skilled posts and management posts of municipal CDCs were 72.3% and 65.6%, and the CVs of county CDCs were 101.6% and 82.1%. In terms of the approved professional titles structural proportion, the degree of dispersion appeared to be higher in senior titles and primary titles approved proportion of municipal CDCs (CV=29.1%, 28.5%), while the degree of dispersion was higher in senior titles and vice-senior titles of county CDCs (CV=58.9%, 21.8%) . Meanwhile, the approved proportions of senior titles in municipal and county CDCs were lower with the averages of 32.2% and 17.0%. The posts of infectious disease prevention and control and laboratory detection were accounting for the majority posts in municipal and county CDCs with average percentages of 47.8% and 45.1% . Conclusion The present situation of post structural proportion meets the relevant requirements generally. However, there are some phenomena of non-standard approved proportion of ground skilled posts and management posts and low senior titles approved proportion. Meanwhile, the percentage of infectious disease prevention and control and laboratory detection posts appears to be lower in county CDCs.

An analysis on the personnel allocation and basic quality structure of middle-level cadres in CDCs of Zhejiang Province / 预防医学

Objective Toanalyzethepersonnelallocationandbasicqualitystructureofmiddle-levelcadresinCDCsof ZhejiangProvince.Methods DatawerecollectedfromthenationalbasicinformationsystemofCDCs.Anddescriptive statistics,chi-square test and Kruskal -Wallis H test were used to analyze the differences of middle -level cadres'personnelallocationandbasicqualityamongthreelevelsofCDCs.Results Theallocationratioofmiddle-levelcadresin management departments was 25.58%,27.32% and 23.58% for provincial level,city level and county level of CDCs respectively,which was 74.42%,72.68% and 76.42% in management departments respectively.There were significant differences in ages,working years,education levels,majors and titles across different levels of CDCs (P<0.05 ).And there were significant differences in education levels across counties with different economic levels (P<0.05 ). Conclusion Thepersonnelallocationofmiddle-levelcadreswithexcellentbasicqualityindifferentlevelsofCDCsin Zhejiang Province was reasonable.

MNPs-Fe₃O₄mediates malignant Hematolpoectic cell apoptosis / 中国实验血液学杂志

This study was purposed to evaluate whether the safe concentration of magnetic nanoparticles of Fe₃O₄(MNPs-Fe₃O₄) for monocytes could induce the SKM-1 cell apoptosis. The average size and Zeta potential of MNPs-Fe₃O₄were determined by transmission electron microscopy and the Malvern Zetasizer 3000 HS, respectively. The cell viability after being exposed to MNPs-Fe₃O₄for 12, 24, 48, and 72 hours was detected by using cell count Kit-8. The cell apoptosis was evaluated by flow cytometry with Annexin V/PI double staining and Wright-Giemsa staining. The cell cycle was measured by flow cytometry. The levels of active caspase-3, survivin and bcl-rambo in cells treated with MNPs-Fe₃O₄and/or trolox for 48 hours were detected with Western blot. The results showed that the cell viability decreased in SKM-1 cells after exposure to 50 µmol/L and 100 µmol/L MNPs-Fe₃O₄(P < 0.05), but did not in monocytes (P > 0.05), compared with that of each non-MNPs-Fe₃O₄-treated group. This exposure also induced the SKM-1 cells to be arrested in G0/G1. Annexin V/PI staining assay showed that cell apoptotic rate induced by 100 µmol/L MNPs-Fe₃O₄was significantly high in SKM-1 cells while not so high in monocytes, and the pretreatment with trolox could attenuate the apoptosis. Moreover, the active caspase-3 increased in SKM-1 cells after the exposure to MNPs-Fe₃O₄, while that was not in monocytes, and the increased expression of BCL-rambo and the decreased expression of survivin involved in the process were also observed. It is concluded that MNPs-Fe₃O₄can induce the caspase 3-dependent SKM-1 cell apoptosis by increasing the BCL-rambo expression and decreasing the survivin expression, but this cytotoxic effect can not be observed in monocyte's.

Effect of shuangshen ningxin formula on energy metabolism of myocardial ischemia/reperfusion rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of Shuangshen Ningxin (SSNX) formula on energy metabolism of myocardial ischemia/reperfusion rats.</p><p><b>METHOD</b>The myocardial ischemia/reperfusion model of Wistar rats was established through the ligation of left anterior descending branch of coronary artery of for 40 min and the reperfusion for 2 h. The Wistar rats were randomly divided into six groups: the sham operation group, the model group, the Trimetazidine group (10 mg x kg(-1)) and SSNX groups (22.5, 45, 90 mg x kg(-1)). Preventive administration was conducted for 5 d. The operation was performed at 1 h on the day of the last administration. CK-MB assay kit was adopted to detect the activity of serum CK-MB. HPLC was used to determine ATP, ADP and AMP contents in myocardial tissues and calculate TAN and EC.</p><p><b>RESULT</b>The preventive administration with SSNX could reduce the activity of serum CK-MB and increase ATP content and EC level in myocardial tissues (P < 0.01 or P < 0.05 vs. the model group).</p><p><b>CONCLUSION</b>SSNX formula can maintain energy charge in cardiomyocytes and relieve ischemia/reperfusion injury by preserving ischemic myocardium ATP.</p>

Expression of MCL-1 and BAK proteins in nutritional anemia and its clinical significance / 中国实验血液学杂志

This study was aimed to investigate the relation of MCL-1 and BAK proteins with incidence and development of nutritional anemia (NA) and their clinical significance. The MCL-1 and BAK protein levels in serum of 66 patients with NA were determined by using ELISA. Eighteen healthy people were randomly selected as normal controls. The results indicated that: (1) as compared with normal control group, the expression level of MCL-1 protein in 3 NA groups (iron-deficiency anemia, macrocytic anemia, mixed anemia) significantly decreased (P < 0.001), while the expression level of BAK protein obviously increased (P < 0.001), but the expression level of MCL-1 and BAK proteins among 3 NA groups showed no obvious differences; (2) the MCL-1 protein expression level increased and BAK protein expression level decreased in 3 NA groups after treatment (P < 0.05). (3) there was negative correlation of expression levels of MCL-1 protein with BAK protein in NA group (r = -0.858 P < 0.05). It is concluded that the MCL-1 and BAK proteins may play an important role in the incidence and development of NA, and can be used as the assist index for defining diagnosis and evaluate prognosis of NA.

Experimental study of jiangtang xiaozhi tablet on decreasing the levels of blood glucose and serum lipids in transgenic mice with diabetes mellitus / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of Jiangtang Xiaozhi Tablet (JTXZT) on decreasing the levels of blood glucose and serum lipids in KK-Ay transgenic model mice with diabetes mellitus (DM).</p><p><b>METHODS</b>KK-Ay transgenic mice were fed with high fat diet to induce DM obesity model. The C57 mice of the same age were recruited as the control group. Then the modeled KK-Ay mice were divided into 5 groups, i.e., the model group, the Pioglitazone Hydrochloride Tablet treatment group (8 mg/kg, as the positive control group), and the high dose JTXZT group (10 g/kg), the middle dose JTXZT group (5 g/kg), and the low dose JTXZT group (2.5 g/kg), 11 in each group. Eight weeks was taken as one therapeutic course. All medicines were given by gastrogavage. The food intake and body weight were measured every week. The blood glucose level was determined once every 2 weeks. The levels of fasting blood glucose (FBG), serum lipids (TC and TG), insulin (INS), and leptin (Lep) were assayed 8 weeks after medication. The weight of liver and fat were weighed to calculate their indices. Then the adipose denaturalization of the liver was classified. The numbers of the pancreatic islet and adipocytes were respectively counted.</p><p><b>RESULTS</b>Compared with the model group, the food intake and the body weight obviously decreased in the 3 JTXZT groups (P < 0.05, P < 0.01). From the 6th week, the FBG level obviously decreased in the high dose JTXZT group (P < 0.01). After eight successive weeks of intragastric administration, the levels of TG and INS obviously decreased in the 3 JTXZT groups (P < 0.05, P < 0.01). The Lep level somewhat decreased in the high dose JTXZT group (P < 0.05). The indices of the liver and fat obviously decreased and the number of the pancreatic islet obviously increased in the 3 JTXZT groups (P < 0.05, P < 0.01). The number of adipocytes obviously decreased in the high and middle dose JTXZT groups (P < 0.05, P < 0.01). The liver fatty degeneration was obviously improved in the high dose JTXZT group (P < 0.05).</p><p><b>CONCLUSION</b>JTXZT had obvious effects on decreasing the levels of blood glucose and serum lipids in KK-Ay transgenic model mice with DM obesity.</p>