Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

With the development of the Scientific, Transparent and Applicable Rankings tool for clinical practice guidelines(STAR), the publication of evaluation and ranking for scientificity, transparency and applicability of Chinese guidelines and consensus published in the medical journals in 2021and 2022, as well as the publication of the STAR evaluation and ranking for some specialities, the STAR evaluation and ranking has received widespread attention in the medical community. In order to further enhance its scientificity and transparency, Methodology and Technology Specialization Committee of the STAR Working Group presents this article to introduce sample identification and speciality assignment in the evaluation and ranking process.

Objective·To investigate the effect of Astragali Radix on T lymphocyte subsets and cytokine expression in Hashimoto's thyroiditis patients with normal thyroid function.Methods·A total of 120 Hashimoto's thyroiditis patients with normal thyroid function and complete data were selected from January 2020 to December 2020 in Jinshan Branch of Shanghai Sixth People's Hospital.The patients were randomly divided into intervention group(n=60)and control group(n=60)by the method of random number table.The treatment plan of the control group was iodine appropriate state diet,and the intervention group was combined with oral Astragali Radix solution(150 mL per time,twice/d)on the basis of the treatment of the control group.The two groups were treated for 6 months.The changes in peripheral blood serum T lymphocyte subsets(CD3+,CD4+,CD8+,and CD4+/CD8+),cytokines[interleukin-2(IL-2),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)],hypersensitive C-reactive protein(hs-CRP),erythrocyte sedimentation rate(ESR),thyroid function,autoantibody,liver and kidney function,and other biochemical indexes were compared before and after treatment between the two groups.Adverse reactions were observed during the treatment.The factors influencing the change amplitude of thyroid peroxidase antibody(TPOAb)were analyzed by multifactor linear regression.Results·Finally,118 patients,with 59 cases in each group,were included in the study.After 6 months of treatment,the intervention group showed significant improvements in the proportions of CD4+ T cells,the ratio of CD4+/CD8+,and the levels of IL-2,TNF-α,IL-10,hs-CRP,ESR,TPOAb,and thyroglobulin antibody(TGAb)compared to the values before treatment and in the control group(P<0.05).There were no statistically significant differences on the above indicators before and after treatment in the control group(P>0.05).No serious adverse reactions were observed in the intervention group.Multiple linear regression analysis results showed that the use of Astragali Radix,increase of CD4+ level,increase of CD4+/CD8+ ratio,and decrease of hs-CRP level were influencing factors for the decrease of TPOAb level(β=-0.393,P=0.029;β=-0.513,P=0.010;β=-0.351,P= 0.035;β=0.434,P=0.023).Conclusion·Astragali Radix can improve the levels of CD4+ T cells,CD4+/CD8+ratio,IL-2,TNF-α,IL-6,and IL-10 in Hashimoto's thyroiditis patients with normal thyroid function,and it is safe to use.

Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation. Thus, 59 patients were included in the present retrospective study, 22 patients in the bevacizumab plus pemetrexed and platinum (B + PP) group, and 37 patients in the pemetrexed and platinum (PP) group. For the entire cohort of patients, the median OS was 33.3 months, and the 1-year and 2-year overall survival rates were 88.5% and 67.8%, respectively. The median OS and 1-year and 2-year OS rates were 20.5 months, 70.3% and 0%, respectively, in the B + PP group and 33.4 months, 97.0% and 89.4%, respectively, in the PP group (P < 0.001). The incidence of grade ⩾ 3 adverse events was higher in the B + PP group than in the PP group (27.3% vs. 10.8%, respectively; P = 0.204). Univariate and multivariate analyses suggested that the receipt of ⩾ 5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS, whereas the addition of bevacizumab was an unfavorable prognostic factor. With increased toxicities, the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.
Aged ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Bevacizumab/adverse effects* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Lung Neoplasms/drug therapy* ; Pemetrexed/adverse effects* ; Platinum/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Objective:To explore the trajectory of breast reconstruction in patients with breast cancer at different stages of treatment and to provide reference for medical staff to intervene in breast reconstruction and improve breast reconstruction rate.Methods:During February 2017-October 2017, 192 female patients with breast cancer (aged 20-64 years, mean 49.7 years) were selected by self-designed breast reconstruction demand questionnaire. They were checked up in the diagnosis period, after chemotherapy without chemotherapy, after chemotherapy, and after the completion of chemotherapy.Results:The demand rates for breast reconstruction during the diagnosis period, the period without chemotherapy after mastectomy, the middle period of chemotherapy and after chemotherapy were 10.4%, 13.4%, 16.7% and 17.7% respectively. The main reasons why patients were unwilling to choose breast reconstruction were that patients were worried that breast reconstruction would affect the integrity of cancer resection and worried about cancer recurrence and metastasis. Patients who were unwilling to breast reconstruction planned to choose breast prosthesis, and the difference was statistically significant ( P<0.05). Menopause was the influencing factor of breast reconstruction demand. Conclusions:After chemotherapy, patients have the highest demand rate for breast reconstruction, and more patients are willing to choose the breast reconstruction method of prosthesis implantation. This period is the best period for medical staff to recommend breast reconstruction treatment.

Objective To investigate the association between serum estradiol levels and macrovascular complication of atherosclerosis in mid-aged and elderly male patients with type 2 diabetes mellitus(T2DM).Methods One hundred and twenty nine male diabetic patients aged over 45 years were recruited in this study.Serum estriol(E2), testosterone(T)and lipid levels were detected using chemiluminescent immunoassay.Carotid ultrasonography was taken to evaluate macrovascular complication of atherosclerosis.The demographic characteristics, clinical features including duration of diabetes and prevalence of carotid atherosclerosis and biochemical features were compared among patients with different serum E2levels.Correlation analysis was also performed using binary logistic analysis.Results There were 43 patients with low serum E2level(<134.1 pmol/L), 44 with intermediate E2level(134.1 -198.2 pmol/L)and 42 with high E2level(>198.2 pmol/L).Among 129 patients the carotid artery lesions were detected in 64 cases.There were significant differences in body weight[(61.0 ±10.4), (67.4 ±13.0)and(76.8 ±10.5)kg,t=3.40,P=0.00], waist circumference[(81.5 ±7.9),(86.6 ± 10.7)and(90.0 ±8.0)cm,t=3.57,P=0.00],body mass index(BMI)[(21.6 ±3.2),(23.5 ±3.8) and(26.2 ±3.0)kg/m2,t=3.72, P=0.00], systolic pressure[(140.2 ±14.8),(143.9 ±18.1)and (155.0 ±13.1)mmHg(1 mmHg=0.133 kPa),t=3.18, P=0.04]and TG[(1.46 ±0.88),(2.23 ± 1.08)and(3.35 ±0.9)mmol/L, t =2.66, P=0.04]among patients with low, intermediate and high serum E2levels.The age-adjusted incidence of carotid atherosclerotic plaque in patients with low, intermediate and high E2levels were 25.6%(11/43),56.8%(25/44)and 66.7%(28/42), respectively (χ2=15.73,P=0.00).Compared to low E2level,the risk ratio of carotid atherosclerosis in intermediate and high E2levels was 1.60(95%CI:1.04-2.46, P<0.05)and 1.80(95%CI:1.17 -2.76, P<0.05),respectively.Conclusion Serum E2level is closely associated with carotid atherosclerotic plaque in middle-aged and elderly male type 2 diabetic patients.

OBJECTIVE:To observe clinical efficacy and safety of Xuebijing injection combined with imipenem and cilasta-tion in the treatment of severe abdominal infection,and its effects on plasma endotoxin and inflammatory factors. METHODS:Dur-ing Apr. 2013-Apr. 2016,100 patients with severe abdominal infection in our hospital were divided into observation group and control group according to random number table,with 50 cases in each group. Both groups were given Imipenem and cilastation sodium for injection 0.5 g added into 0.9% Sodium chloride injection 500 mL,ivgtt(≥40 min),q12 h. Eight hours later,ob-servation group was additionally given Xuebijing injection 100 mL added into 0.9% Sodium chloride injection 500 mL,ivgtt, bid;Both groups were treated for 5-7 d. The levels of plasma endotoxin and inflammatory factors(TNF-α,IL-6,IL-6/IL-10) were compared in 2 groups before after treatment,and clinical efficacies and the occurrence of ADR was recorded. RESULTS:Before treatment,there was no statistical significance in plasma endotoxin or inflammatory factor levels between 2 groups(P>0.05). After treatment,plasma endotoxin and inflammatory factor levels of 2 groups were decreased significantly,and the obser-vation group was significantly lower than the control group,with statistical significance(P<0.05). The excellent and good rate of observation group was 98.00%,which was significantly higher than 78.00%,with statistical significance(P<0.05). No obvi-ous ADR was found in 2 groups. CONCLUSIONS:Xuebijing injection combined with imipenem and cilastation show significant therapeutic efficacy for severe abdominal infection,can effectively control the release of endotoxin and inflammatory factors with good safety.

Objective To explore the effect of TCM external treatment on the patients with hyperplasia of mammary glands by meta-analysis.Methods Literatures about TCM external treatment on the patients with hyperplasia of mammary glands that were published on domestic or international magazines were extensively solicited and assessed with uniform effect criteria. The total number and valid number of patients in these literatures were counted, and the literatures were also assessed and chosen by meta-analysis with Review Manager 5.3.OR values and a 95% confidence interval (CI) were calculated and consolidated.Results Finally, totally 11 literatures and 945 patients were included in our study, of which 464 received TCM external treatment, an effective rate of 89.22%, while the control group included a total of 481 patients, an effective rate of 82.33%. TCM external treatment showed the same effect on hyperplasia of mammary glands as the oral liquid of Chinese medicines, massage and acupuncture did [OR=1.91,95%CI (0.74-4.97)]. When comparing the effect of TCM external treatment and Rupixiao oral liquid on hyperplasia of mammary glands, totally 6 literatures and 509 patients were included in the study, of which 258 received TCM external treatment, an effective rate of 97.29%, while 251 patients took Rupixiao oral liquid, an effective rate of 88.45%. TCM external treatment had a significantly better effect than Rupixiao oral liquid [OR=4.52,95%CI (1.98-10.33)].Conclusions TCM external treatment has the same effect with oral liquid of Chinese medicines, massage and acupuncture, while TCM external treatment on hyperplasia of mammary glands which promotes the circulation of qi and blood and eliminates phlegm and frees channels has a significantly better effect than Rupixiao oral liquid. It suggests that in our clinical work we should treat patients based on whatever methods they can withstand so as to improve their satisfaction.

Objective: This research explores the relationship between the immuno-suppression function of regulatory T cells (Treg) in the ascites of ovarian cancer (OC) patients, the clinico-pathologic features of these patients, and the correlation of the function of Treg with initial treatment and relapse status of the patients to further investigate the specific mechanism of immuno-regulatory func-tion of CD4+ CD25+ Treg in the ascites of OC. Methods: Immuno-magnetic activated cell sorting (MACS) was conducted to sort CD4+CD25+Treg and autologous CD4+CD25-Treg from the ascites of 28 OC patients. Carboxyfluorescein-diacetate succinimidyl ester (CFSE) was used to label the autologous CD4+CD25-Treg. These labeled cells were then used as controls and co-cultured with autologous CD4+CD25+Treg at the ratio of 1∶1 or 1∶2. The mean inhibition ratio of Treg in specimens to the proliferation of autolo-gous CD4+ CD25-Treg was calculated after the flow cytometry of the CFSE expression and Modfit software analysis of the CD4+CD25-Treg proliferation index (PI) were performed. Anti-IL-10 and/or anti-TGF-β1 antibodies were neutralized to investigate whether the CD4+CD25+Treg-mediated immuno-suppression escaped through the ascites can produce a marked effect by the inhibitory cyto-kine IL-10 or TGF-β1. Results: The mean inhibition ratio of CD4+ CD25- Treg in the ascites of stage Ⅲ to Ⅳ OC patients was (75.72±17.04)%, which is significantly higher than that of stageⅠtoⅡOC patients (59.61±16.97)%;P<0.05. In addition, Treg in the as-cites of OC patients with recurrent disease showed a significantly higher inhibition ratio than that of patients with primary disease;P<0.001. Moreover, Treg in groups added into neutralizing anti-IL-10 and/or anti-TGF-β1 antibodies displayed significantly lower depres-sant effect than the control group;P<0.05. Conclusion:The immuno-suppression of CD4+CD25+Treg in the ascites of OC patients is correlated with the tumor staging and status of the primary or recurrent diseases. Moreover, Treg may indicate a suppressor function by secreting cytokine IL-10 and TGF-β1.

Objective:CD4+CD25+regulatory T cells (Treg) may contribute to tumor progression by suppressing antitumor im-munity. The function of Treg in antitumor immunity regulation in the peritoneal microenvironment of ovarian cancer (OC) was investi-gated and compared with the circulating Treg to elucidate OC immune escape. Methods: Flow cytometry was used to determine the proportion of CD4+CD25+T cells in CD4+T cells in ascites of 27 patients with OC and in peripheral blood lymphocytes of 28 patients with OC. The samples were analyzed and classified in three stages:primary disease (PD), after chemotherapy (AC), and recurrence dis-ease (RD), according to the clinical conditions of the OC patients upon donating the samples. The percentage of Treg in the three groups was determined in ascites and blood. CD4+CD25+T cells were isolated from ascites and peripheral blood of patients with OC us-ing magnetic sorting (MACS) system. The cells were then tested for regulatory function through coculture with carboxyfluorescein diac-etate succinimidyl ester-labeled autologous CD4+ CD25- responder cells. Results:The proportion of CD4+ CD25+T cells in CD4+T cells significantly increased in ascites (28.25%± 14.06%) compared with that in blood (14.6%± 4.74%;P<0.0001). The Treg in ascites and blood in AC showed higher proportion (P<0.0001) than those in the PD and RD;the proportion in RD was higher than that in PD (P<0.0001). Moreover, the Treg in ascites mediated a significantly higher suppression compared with the Treg in peripheral blood (P<0.001). Conclusion:The frequency and suppressor function of Treg were significantly higher in ascites than in peripheral blood. This finding suggests more possibility for escape immune surveillance in the peritoneal microenvironment. Moreover, the proportion of Treg in AC was higher than that in PD or RD;the proportion in RD was higher than that in the PD. Chemotherapy may favor the expansion of Treg, which may promote the recurrence of cancer.