This article aims to explore the effect and mechanism of Liujunzi Pills on the intestinal microbiota of rats with spleen Qi deficiency syndrome. The raw Rhei Radix et Rhizoma water extract(1 g·mL~(-1)) was used to prepare spleen Qi deficiency rat models. A total of 44 SD male rats were randomly divided into a control group, a model group, Liujunzi Pills groups at high(3.24 g·kg~(-1)), medium(1.62 g·kg~(-1)), low(0.81 g·kg~(-1)) doses, and Shenling Baizhu San(2.50 g·kg~(-1)) group. The drug effect was evaluated by observing the following aspects: spleen index, fecal water content, body weight, and intestinal propulsion index. Gut microbiota analysis and 16S rRNA gene sequencing were conducted on feces. Enzyme-linked immunosorbent assay(ELISA) and UV spectrophotometry were used to detect interleukin-1β(IL-1β) and adenosine triphosphate(ATP) levels in small intestine tissues. Hematoxylin-eosin staining and transmission electron microscopy were employed to observe changes in intestinal pathology and microstructure. The results show that, compared with the control group, fecal moisture content is significantly increased while spleen index, body weight, and intestinal propulsion index are significantly reduced in rats of the model group, indicating the successful establishment of the model. The above symptoms can be improved by both Shenling Baizhu San and Liujunzi Pills. Compared with the control group, in the model group, the gut microbiota abundance is changed with an unbalanced development: the abundance of beneficial bacteria within the Bacteroidetes phylum is reduced, accompanied by a significantly decreased Shannon index, and reduced signal levels of nicotinamide adenine dinucleotide phosphate(NADPH)-related enzymes relevant to mitochondria. However, Liujunzi Pills and Shenling Baizhu San can significantly improve the Bacteroidetes phylum abundance in gut microbiota, microbial diversity, and NADPH activity in the model group. Additionally, compared with the control group, the ATP level is decreased and the IL-1β level is increased in small intestinal tissues of the model group, with shorter small intestinal epithelial villi and decreased mitochondrial number. The above symptoms can be improved by Liujunzi Pills and Shenling Baizhu San. In conclusion, Liujunzi Pills can treat spleen Qi deficiency syndrome by enhancing mitochondrial function to regulate gut microbiota balance and diversity.
Animals ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Rats, Sprague-Dawley ; Rats ; Qi ; Spleen/metabolism* ; Splenic Diseases/metabolism* ; Humans ; Interleukin-1beta/genetics* ; Bacteria/drug effects* ; Feces/microbiology* ; Adenosine Triphosphate/metabolism*

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

Objective To investigate the trends of major thyroid function indices in Chinese adolescent females at different ages and the differences from adult reference intervals.Methods A total of 791 female students from 4 junior high schools were enrolled in the study by selecting one junior high school in each of the following locations:Minhang District of Shanghai,Haimen City of Jiangsu Province,Yuhuan City of Zhejiang Province,and Deqing County of Zhejiang Province from Oct to Nov 2017 and from Jan to Mar 2019.The subjects were subjected to physical examination as well as thyroid hormone levels;and the Pubertal Developmental Events Self-Assessment Scale(PDS)was used to evaluate the staging of pubertal development.Follow-ups were conducted after 2 years,with the same survey content.Thyroid function levels were assessed in 5 age groups between 11 to 15 years old,95%CI were calculated,and mixed linear models were used to analyze the effects of age and pubertal developmental stage on hormone levels.Results The reference intervals for thyroid stimulating hormone(TSH),free triiodothyronine(FT3)and free thyroxine(FT4)in adolescent females differed significantly from those of adults,with misclassification rates ranging from 2.98%to 5.17%.Statistically significant differences were found for age,pubertal development staging,and the interaction of age and pubertal staging after correcting for BMI,waist circumference(all P<0.05).TSH levels were more affected by age before the completion of pubertal development,the level of the 12-year-old group was higher than that of the 11-year-old group(P=0.001 2)and the 13-year-old group(P<0.000 1);FT3 levels showed greater variability with age during late pubertal stage,with levels significantly higher at 13 years of age than at 11 and 12 years of age(P<0.0001),and gradually decreasing after 13 years of age(P<0.000 1).In contrast,FT4 levels were generally less affected by age between 11 and 15 years of age,with levels slightly higher at 13-15 years of age than at 11-12 years of age(P<0.000 1).Conclusion The levels of TSH,FT3,and FT4,as indicators of thyroid function in adolescent females,differ significantly from those of adults,and are differently affected by age and the stages of pubertal development;further refinement of the reference intervals for age-and pubertal-development-specific thyroid indicators is necessary.

Purpose To explore the molecular features of diffuse large B-cell lymphoma(DLBCL)with high expression of MYC.Methods The clinical data of 45 cases of DLBCL were collected.Immunohistochemical EnVision method was used to classify the patients into the group with high expression of MYC and the group with low expression of MYC.All samples were subjected to DNA targeted sequencing and molecular typing was performed using the LymphGen online tool.Cellular origin was determined by using the Lymph2Cx method.The correlation be-tween MYC overexpression and clinicopathological parameters was analyzed by the x2 test and Fisher precise test.Survival curves were drawn and survival-related factors were analyzed u-sing Cox univariate and multivariate regression.ResultsCases were classified into DLBCL with high expression of MYC(n=17)and DLBCL with low expression of MYC(n=28).Com-pared to the group with low expression of MYC,the group with high expression of MYC had more PIM1,MYD88,CD79B,CD58 and PRDM1 mutations(76.5％vs 28.6％,70.6％vs 32.1％,58.8％vs28.6％,29.4％vs3.6％,29.4％vs 3.6％,P＜0.05),MCD were more frequently found(58.8％vs 10.7％,P=0.001),GCB were rarely found(17.6％vs 50.0％,P=0.030).Overall survival was significantly shorter in DLBCL with high expression of MYC(P＜0.05).Cox multi-factorial analysis showed that age was an independent prognostic factor for DLBCL(P＜0.05).Conclusion Patients with high expression of MYC were frequently characterized as MCD and ABC,and PIM1,MYD88,CD79B,CD58 and PRDM1 muta-tions were common.Patients with high expression of MYC had a poorer prognosis.

Objective To evaluate the bioequivalence of the test preparation and reference preparation of azithromycin capsules in healthy Chinese subjects.Methods A total of 48 subjects were enrolled in this study using a randomized,open,two-sequence,cross design.Each subject received a single oral dose of azithromycin capsules test drug(T)or reference drug(R)for 250 mg.The concentrations of azithromycin in plasma were determined by Liquid Chromatograph Mass Spectrometer,and the pharmacokinetic parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.Results The main pharmacokinetic parameters of azithromycin after a single fasting dose of the test drug and the reference drug were as follows:the Cmax were respectively(319.89±127.35)and(330.41±122.11)ng·mL-1;AUC0-192h were respectively(2 423.04±587.15)and(2 489.97±685.73)ng·h·mL-1;AUC0-∞ were respectively(2 753.40±644.96)and(2 851.71±784.05)ng·h·mL-;tmax were respectively(2.60±1.11)and(2.62±1.13)h;t1/2 were respectively(76.76±15.14)and(79.83±17.14)h.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-192h and AUC0-∞ of T and R were 87.52％-107.18％,91.46％-105.80％and 91.17％-105.06％,respectively.Conclusion The test preparation of azithromycin capsule was bioequivalent to the reference preparation under fasting condition.

AIM: To compare the clinical efficacy, vault, and rotational stability of horizontal, oblique, and vertical implantation of Toric implantable collamer lens(TICL).METHODS: Retrospective cohort study. A total of 92 cases(120 eyes)who underwent TICL implantation from July 2018 to March 2022 and had regular follow-up for at least 1 a postoperatively(1 d, 1 wk, 1, 3, 6 mo, and 1 a)at Wuhan Bright Eye Hospital were collected. The patients were divided into three groups, with 34 cases(45 eyes)in horizontal implantation group, 25 cases(29 eyes)in oblique implantation group(29 cases), and 33 cases(46 eyes)in vertical implantation group. Uncorrected distance visual acuity(UDVA), corrected distance visual acuity(CDVA), diopters, vault, and rotation angle(deviation of the actual axis of TICL from the expected axis).RESULTS: All surgeries were uneventful, and there were no complications such as infection, secondary glaucoma, or cataract opacity. Safety and efficacy of the surgery: the CDVA of the three groups of patients was better than or equal to the preoperative CDVA at 1 a postoperatively, and there was no statistically significant differences in postoperative UDVA and CDVA of the three groups(P>0.05). The safety index at 1a postoperatively was 1.34±0.21, 1.34±0.17, and 1.31±0.18 for the horizontal, oblique, and vertical groups, respectively. The efficacy index was 1.26±0.21, 1.33±0.18, and 1.27±0.16 for the three groups, respectively, both with no statistically significant differences(P>0.05). Vault: there was a significant difference in postoperative vault among the three groups(P=0.003), with the vertical group having the lowest vault, followed by the horizontal group and the oblique group. The vaults at different follow-up time points within each group showed significant differences(P<0.001), and all decreased over time. Residual astigmatism: there was no significant difference in residual astigmatism among the three groups(P=0.130), but there were differences at different follow-up time points within each group(P<0.001). Rotation angle: no significant differences in rotation angle were observed among the three groups(P=0.135), but there were differences at different follow-up time points within each group(P<0.001).CONCLUSION: The implantation of TICL in different orientations has good safety and efficacy, the postoperative rotational stability is good, and the appropriate angle can be selected to implant TICL according to the clinical situation.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

To study the residue and dietary risk of propiconazole in Panax notoginseng and the effects on physiological and bioche-mical properties of P. notoginseng, we conducted foliar spraying of propiconazole on P. notoginseng in pot experiments. The physiolo-gical and biochemical properties studied included leaf damage, osmoregulatory substance content, antioxidant enzyme system, non-enzymatic system, and saponin content in the main root. The results showed that at the same application concentration, the residual amount of propiconazole in each part of P. notoginseng increased with the increase in the times of application and decreased with the extension of harvest interval. After one-time application of propiconazole according to the recommended dose(132 g·hm~(-2)) for P. ginseng, the half-life was 11.37-13.67 days. After 1-2 times of application in P. notoginseng, propiconazole had a low risk of dietary intake and safety threat to the population. The propiconazole treatment at the recommended concentration and above significantly increased the malondialdehyde(MDA) content, relative conductivity, and osmoregulatory substances and caused the accumulation of reactive oxygen species in P. notoginseng leaves. The propiconazole treatment at half(66 g·hm~(-2)) of the recommended dose for P. ginseng significantly increased the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) in P. notoginseng leaves. The propiconazole treatment at 132 g·hm~(-2) above inhibited the activities of glutathione reductase(GR) and glutathione S-transferase(GST), thereby reducing glutathione(GSH) content. Proconazole treatment changed the proportion of 5 main saponins in the main root of P. notoginseng. The treatment with 66 g·hm~(-2) propiconazole promoted the accumulation of saponins, while that with 132 g·hm~(-2) and above propiconazole significantly inhibited the accumulation of saponins. In summary, using propiconazole at 132 g·hm~(-2) to prevent and treat P. notoginseng diseases will cause stress on P. notoginseng, while propiconazole treatment at 66 g·hm~(-2) will not cause stress on P. notoginseng but promote the accumulation of saponins. The effect of propiconazole on P. notoginseng diseases remains to be studied.
Panax notoginseng/chemistry* ; Panax ; Antioxidants/pharmacology* ; Saponins/pharmacology* ; Glutathione ; Risk Assessment

OBJECTIVE: To assess the influence of FLT3 expression on the prognosis of patients with acute myeloid leukemia (AML) by cell experiment and clinical data analysis. METHODS: Models for FLT3 over-expression and interference-expression in AML cells were constructed. The level of BAK gene expression and its protein product was determined, along with the proliferation and apoptosis of leukemia cells. FLT3 gene expression and FLT3-ITD variant were determined among patients with newly diagnosed AML. RESULTS: Compared with the interference-expression group, the level of BAK gene expression and its protein in FLT3 over-expression AML cells was significantly lower (P < 0.001), which also showed significantly faster proliferation (P < 0.001) and lower rate of apoptosis (P < 0.001). The expression level of FLT3 gene among patients with newly diagnosed AML was also significantly higher compared with the healthy controls (P < 0.001). The FLT3 gene expression of FLT3-ITD positive AML patients was higher than that of FLT3-WT patients (P = 0.002). Survival analysis showed that AML patients with high FLT3 expression in the medium-risk group had a lower complete remission rate and overall survival rate compared with those with a low FLT3 expression (P < 0.001). CONCLUSION Over-expression of FLT3 may influence the course of AML by promoting the proliferation of leukemia cells and inhibiting their apoptosis, which in turn may affect the prognosis of patients and serve as a negative prognostic factor for AML.
Humans ; Apoptosis/genetics* ; Data Analysis ; Leukemia, Myeloid, Acute/genetics* ; Gene Expression ; fms-Like Tyrosine Kinase 3/genetics*