This paper aimed to study phenylpropanoids of Tripterygium hypoglaucum. Twenty-four compounds were isolated from the 70% EtOH extracts of T. hypoglaucum by silica gel column chromatography, reversed phase column chromatography, gel column chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography. Compounds 1-3 were three new phenylpropionds. Their structures were identified by ultraviolet spectrum, infrared spectroscopy, high resolution electrospray ionization mass spectrometry, and nuclear magnetic resonance data as: threo-2-(4-hydroxy-3-methoxyphenoxy)-3-(4-hydroxy-3-methoxyphenyl)-1,3-propanedol (1), erythro-2-(4-hydroxy-3-methoxyphenoxy)-3-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (2), erythro-3-(4-hydroxy-3,5-dimethoxyphenyl)-3-ethoxypropane-1,2-propanediol (3). Compounds 4-6, 9, 14, 15, 18, 19, and 21-24 were obtained from Tripterygium genus for the first time. The cytotoxicity assay of cancer cells suggested that compound 20 displayed cytotoxicity on the breast cancer 4T1 cells whose 50% inhibitory concentration was 125.60 μmol·L^-1.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

Purpose::The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway.Methods::We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant. Results::Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F= 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F= 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F= 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F= 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F= 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F= 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression. Conclusions::CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Tinnitus is a clinically refractory disease with a high incidence.LAI's Tongyuan acupuncture method believes that tinnitus is nothing more than the two ends of deficiency and excess.The deficiency is closely related to original spirit,and the excess is related to the pathological factors such as externally-contracted six pathogenic factors,phlegm-damp and blood stasis,and qi stagnation and yang constraint.The Tongyuan acupuncture method is based on original spirit,takes the two vessels of conception vessel(CV)and governor vessel(GV)as the general outline,takes the regulation of yin and yang as the main method,pays attention to the combination of local and overall,and emphasizes the application of tonification and purgation,and has the clinical effect of reinforcing healthy qi and dispelling pathogen,cultivating the vital essence.In clinical application,the method of'unblocking governor vessel and nourishing spirit'is used to play the role of heart and brain nourishing spirit and warming and supporting yang qi.The method of'conducting qi back to its source'has the effect of cultivating the vital essence and regulating qi movement.The treatments should be cooperated according to the syndromes,so that the pathogens can be expelled and healthy qi can be settled.Qi and blood have origins of generation and transformation and normally nourishing in the ear,so as to effectively alleviate the patient's tinnitus symptoms.This paper summarizes and analyzes Professor LAI Xin-Sheng's Experience in the diagnosis and treatment of tinnitus by Tongyuan acupuncture method,and provides a new acupuncture treatment plan for clinical application.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective:To analyze the predictive value of age-adjusted Charlson comorbidity index (ACCI) on the risk of falls in elderly patients with femoral neck fractures.Methods:This study was a retrospective cohort study. From June 2021 to June 2022, cluster sampling was used to select 1 050 patients with femoral neck fractures at the Honghui Hospital affiliated with Xi'an Jiaotong University as the study subject. This study calculated the total ACCI score based on patient comorbidities, and divided patients into a low-risk fall group ( n=282) and a high-risk fall group ( n=768) based on whether the fall risk factor assessment score was ≥4.This study compared the differences in age, gender, American Society of Anesthesiologists (ASA) grading, ACCI score, white blood cell count, red blood cell count, platelet count, lymphocyte count, serum albumin, hemoglobin, creatinine, and urea nitrogen between the two groups. Independent variables with P<0.05 were included in binary Logistic regression to analyze the factors affecting the risk of falls in patients, and a receiver operating characteristic (ROC) curve was plotted. Results:There were statistically significant differences in age, ASA grading, red blood cell count, lymphocyte count, ACCI score, serum albumin, hemoglobin, creatinine, and urea nitrogen between the two groups of patients ( P<0.05). Logistic regression analysis found that age, ASA score, and ACCI score were independent risk factors for fall risk ( P<0.05), while serum albumin was an independent protective factor for fall risk ( P<0.05). The area under the ROC curve of ACCI for predicting fall risk was 0.892, and a score of 4 in ACCI was the cutoff value for predicting fall risk. Conclusions:ACCI can serve as an auxiliary tool for evaluating and predicting the risk of falls in elderly patients with femoral neck fractures, and can provide reference for clinical screening of high-risk individuals for falls.

This is the first reported case of a female with monkeypox infection in Kunming City,Yunnan Province.An epi-demiological investigation was conducted to provide a scientific basis for the prevention and control of monkeypox epidemics in China,especially for early detection in females in accordance with the"Monkeypox prevention and control program(2023 ver-sion)".Diagnosis was performed as described in the"Monkeypox Diagnosis and Treatment Guidelines(2022 version)".Speci-mens were collected for laboratory testing.The epidemiological investigation determined that the female patient had sexual in-tercourse with her newly married husband once before disease onset and the husband hid his history of male homosexual sex.The laboratory test results of the woman and her husband were positive for the nucleic acid of the monkeypox virus.Both had typical clinical symptoms,including rash.The epidemiological investigation,clinical symptoms,laboratory test results,and previous epidemic data of monkeypox in Yunnan province confirmed the woman as the first female infected with monkeypox in Yunnan Province and her husband was the presumed source of infection.

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Objective: To investigate the association between chronic lung diseases and the risk of lung cancer. Methods: Using UK Biobank (UKB) survey data, 472 397 participants who had not previously been diagnosed with cancer and whose self-reported sex was consistent with their genetic sex were studied. Information on the prevalence of previous chronic lung diseases, general demographic characteristics and the prevalence of lung cancer was collected using baseline questionnaires and national health system data. The multivariate Cox proportional risk regression model was used to analyze the association between four previous chronic lung diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and interstitial pulmonary disease) and the risk of lung cancer. A total of 458 526 participants with genotype data in the observational study were selected as research objects, and the closely related and independent genetic loci with four chronic lung diseases were selected as instrumental variables, and the association between four chronic lung diseases and the risk of lung cancer was analyzed by Mendelian randomization (MR). The dose-response relationship between genetic risk score and the risk of lung cancer in different chronic lung diseases was evaluated using a restricted cubic spline function. Results: The age [M (Q₁, Q₃)] of the subjects was 57 (50, 63) years old, and there were 3 516 new cases of lung cancer (0.74%) during follow-up. The multivariate Cox proportional hazard regression model analysis showed that previous chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, about 1.61 (1.49-1.75) and 2.61 (1.24-5.49), respectively. MR Studies showed that genetically predicted chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, with HR (95%CI) of 1.10 (1.03-1.19) and 1.04 (1.01-1.08), respectively. The results of restricted cubic spline function analysis showed that the risk of lung cancer increased linearly with the increase of genetic risk scores for chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (P<0.05). Neither observational studies nor Mendelian randomization analysis found an association between previous asthma or interstitial lung disease and the risk of lung cancer (both P values>0.05). Conclusion: Chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis are potential risk factors for lung cancer.
Humans ; Middle Aged ; Mendelian Randomization Analysis ; Biological Specimen Banks ; Lung Neoplasms/genetics* ; Pulmonary Disease, Chronic Obstructive/genetics* ; Asthma/genetics* ; Idiopathic Pulmonary Fibrosis/genetics* ; United Kingdom/epidemiology* ; Genome-Wide Association Study

Objective:To investigate the clinical effect of Shenqi Dihuang Decoction and Xiaochengqi Decoction enema combined with hemodialysis in the treatment of qi deficiency, blood stasis and dampness and turbidity in chronic kidney disease (CKD) stage 5.Methods:Randomized controlled trial. A total of 102 elderly CKD stage 5 patients with Qi and Yin deficiency and turbid poison inherent type were selected from May 2021 to January 2022 of the Beijing Longfu Hospital. The patients were divided into two groups by random number table method. Control group (51 cases) received hemodialysis treatment for 4 weeks, and the observation group (51 cases) received Shenqi Dihuang Decoction and Xiaochengqi Decoction enema combined with hemodialysis treatment for 4 weeks. The levels of BUN, SCr and β2-microglobulin (β2-MG), and K +, Ca 2+, P 3- content, hemoglobin were detected by automatic blood cell analyzer, and serum CRP and IL-6 levels were detected by latex enhanced immune scattering turbidimetry. The adverse reactions during the treatment and evaluate the clinical efficacy were observed and recorded. Results:During the treatment, 2 patients in the observation group withdrew from the study due to severe diarrhea, and other patients completed the study. There were significant differences in total response rate between observation group and control group [91.84%(45/49) vs. 74.51%(38/51); χ2=5.32, P=0.002]. After treatment, scores of lumbar and knee acerbity, tiredness and fatigue, edema, dizziness and tinnitus, fear of cold and warm, yellow face, dry stool and total score in observation group were significantly lower than those in the control group ( t=8.38, 13.44, 15.14, 13.09, 7.12, 7.73, 11.16, 11.45, P<0.01); the scores of SF-12-PCS and SF-12-MCS were significantly higher than those in the control group ( t=3.24, 4.22, P<0.01). After treatment, levels of serum BUN [(15.02±2.35)mmoL/L vs. (18.02±3.65)mmoL/L, t=4.87], SCr[(155.26±23.65) μmol/L vs. (184.49±35.49) μmol/L, t=4.83], β2-MG[(7.12±1.27)mg/L vs. (9.56±2.14)mg/L, t=6.90] and P 3-[(1.51±0.10) mmol/L vs. (2.02±0.19) mmol/L, t=16.70], K +[(3.65±0.54) mmol/L vs. (4.21±0.63)mmol/L, t=4.76] in observation group were significantly lower than those in the control group ( P<0.01); Ca 2+[(1.86±0.36)mmol/L vs. (2.35±0.42)mmol/L, t=6.25] was significantly higher than that of the control group ( P<0.01). No adverse reactions occurred during the treatment in the two groups ( P>0.05). Conclusion:Shenqi Dihuang Decoction and Xiaochengqi Decoction enema and hemodialysis can improve renal function, correct electrolyte disorder, reduce the level of inflammatory factors, improve the quality of life, and improve the therapeutic effect of the patients with CKD stage 5 and Qi and Yin deficiency and turbid poison inherent pattern.