In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

The identification of the components absorbed in serum of platycosides in total saponins fraction of Platycodonis Radix is great significance, but there are still great challenges. In this study, 8 types of 44 primordial components from Platycodon saponins were firstly identified using the ultra-performance liquid chromatography-linear ion trap electrostatic field orbitrap high resolution mass spectrometry (UPLC-LTQ-Orbitrap-MS) equipped with the software of Compound Discoverer 3.2 and Trace finder 2.1. Then, the platycosides and their deglycosylated metabolites were used as the template molecules to construct the intestinal microbiota mediated method to identify the primary components and the prototypes in serum. As results, 57 components originating from 44 prototypes of platycosides were identified from drug-containing plasma. Those compounds consist of 12 prototypes of platycosides and 45 metabolites, while the prototypes in serum are also deglycosylated metabolites of other platycosides. The results showed that the intestinal microbiota mediated method could be applied to identify the metabolites of platycosides in total saponins fraction of Platycodonis Radix; and reveal the potential existing forms of prototypes of platycosides in plasma; In addition, it could clearly illustrate the one to many and many to one network of the prototypes and metabolites of platycosides. All animal protocols were approved by the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (No.JZLLSC-202100322).

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.
Female ; Humans ; Uterine Cervical Neoplasms/pathology* ; Neoplasm Staging ; Lymphatic Metastasis ; Lymph Node Excision ; Retrospective Studies ; Prognosis ; Chemoradiotherapy/methods* ; Carcinoma, Squamous Cell/pathology*

BACKGROUND: Prospective analyses have yet to identify a consistent relationship between sleep duration and the incidence of gastrointestinal (GI) cancers. The effect of changes in sleep duration on GI cancer incidence has scarcely been studied. Therefore, we aimed to examine the association between baseline sleep duration and annual changes in sleep duration and GI cancer risk in a large population-based cohort study. METHODS: A total of 123,495 participants with baseline information and 83,511 participants with annual changes in sleep duration information were prospectively observed from 2006 to 2015 for cancer incidence. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and their confidence intervals (CIs) for GI cancers according to sleep duration and annual changes in sleep duration. RESULTS: In baseline sleep duration analyses, short sleep duration (≤5 h) was significantly associated with a lower risk of GI cancer in females (HR: 0.31, 95% CI: 0.10-0.90), and a linear relationship between baseline sleep duration and GI cancer was observed (P = 0.010), especially in males and in the >50-year-old group. In the annual changes in sleep duration analyses, with stable category (0 to -15 min/year) as the control group, decreased sleep duration (≤-15 min/year) was significantly associated with the development of GI cancer (HR: 1.29; 95% CI: 1.04-1.61), especially in the >50-year-old group (HR: 1.32; 95% CI: 1.01-1.71), and increased sleep duration (>0 min/year) was significantly associated with GI cancer in females (HR: 2.89; 95% CI: 1.14-7.30). CONCLUSIONS Both sleep duration and annual changes in sleep duration were associated with the incidence of GI cancer.
Cohort Studies ; Female ; Gastrointestinal Neoplasms/etiology* ; Humans ; Incidence ; Male ; Middle Aged ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Sleep

Objective: To determine the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Methods: In this prospective cohort study, hypertensive patients from the Kailuan Study, who were diagnosed in 2006-2007 check-up, were screened for enrollment. Participants who finished the biennial follow-up until December 31, 2017 were finally included in this analysis. The primary outcome was incident diabetes development. The pulse pressure variables were divided into quartiles (Q₁-Q₄), and the Kaplan-Meier curve was used to examine and estimate the cumulative incidence of new-onset diabetes among quartiles. Cox proportional hazards regression model was performed to explore the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Results: During an average follow-up of 8.17 years, 6 617 new-onset diabetes were identified out of the 32 917 hypertensive patients with no history or evidence of diabetes in 2006-2007 check-up. Participants were classified into quartiles according to pulse pressure levels as follows: Q₁ group(<41 mmHg (1mmHg=0.133kPa))(n=7 995); Q₂ group(41-<51 mmHg) (n=8 196); Q₃ group (51-<61 mmHg) (n= 8 270); Q₄ group (≥61 mmHg) (n=8 456). The cumulative incidences of new-onset diabetes across the quartiles were 16.94%, 19.61%, 21.07%, and 22.33%, respectively, with the incidence density was 20.27, 23.20, 24.92, and 26.10 per 1 000 person-years, respectively. The cumulative incidence of new-onset diabetes increased in proportion with increasing pulse pressure levels (P<0.01 by the Log-rank test). After multivariate adjustment, compared with the first quartile, the hazard ratios for new-onset diabetes in the third and fourth quartiles were 1.13 (95%CI 1.04-1.22, P<0.01) and 1.14 (95%CI 1.05-1.24, P<0.01), respectively. The risk of new-onset diabetes increased 5%(HR=1.05, 95%CI 1.02-1.08, P<0.01) with the fractional pulse pressure increased per 1 SD (0.13). Findings from the three sensitivity analyses were consistent with the main results in this cohort. Conclusions: Pulse pressure at baseline is positively associated with the incidence of new-onset diabetes among hypertensive individuals, and pulse pressure is an independent risk factor for the development of diabetes in hypertensive patients.

OBJECTIVE: To observe the effect of ginger-partitioned moxibustion on digestive tract reaction, quality of life and white blood cell count after chemotherapy in advanced malignant bone tumors patients. METHODS: A total of 64 patients were randomly divided into an observation group and a control group, 32 cases in each group. Both groups were treated with adriamycin combined with cisplatin (AP) chemotherapy. The patients in the control group were treated by tropisetron hydrochloride intravenous on preventing the vomiting 1 h before receiving chemotherapy. On the basis of the control group, the patients in the observation group were treated with ginger-partitioned moxibustion at Neiguan (PC 6), Zusanli (ST 36), Shenque (CV 8), and Zhongwan (CV 12) 2 h after chemotherapy, once a day, 30 min each time. The course of chemotherapy, ginger-partitioned moxibustion and tropisetron hydrochloride intravenous was 5 days. The digestive tract reaction rating, quality of life score and white blood cell count were compared 1 d before chemotherapy, 2 d after chemotherapy and 7 d after chemotherapy between the two groups. RESULTS: The number of 0 grade in digestive tract reaction 2 d and 7 d after chemotherapy in the observation group was significantly higher than that in the control group ( CONCLUSION Ginger-partitioned moxibustion can prevent and treat vomiting after chemotherapy in advanced malignant bone tumors, and improve the quality of life and white blood cell count of patients.
Acupuncture Points ; Bone Neoplasms/drug therapy* ; Ginger ; Humans ; Moxibustion ; Quality of Life ; Vomiting/etiology*

The pain-relieving effect of acupuncture is known to involve primary afferent nerves (PANs) via their roles in signal transmission to the CNS. Using single-unit recording in rats, we characterized the generation and transmission of electrical signals in Aβ and Aδ fibers induced by acupuncture-like stimuli. Acupuncture-like signals were elicited in PANs using three techniques: manual acupuncture (MAc), emulated acupuncture (EAc), and electro-acupuncture (EA)-like peripheral electrical stimulation (PES). The discharges evoked by MAc and EAc were mostly in a burst pattern with average intra-burst and inter-burst firing rates of 90 Hz and 2 Hz, respectively. The frequency of discharges in PANs was correlated with the frequency of PES. The highest discharge frequency was 246 Hz in Aβ fibers and 180 Hz in Aδ fibers. Therefore, EA in a dense-disperse mode (at alternating frequency between 2 Hz and 15 Hz or between 2 Hz and 100 Hz) best mimics MAc. Frequencies of EA output >250 Hz appear to be obsolete for pain relief.

Objective:To systematically investigate the chemical constituents of 90% ethanol extract of Corydalis impatiens，and evaluate their inhibitory effect on cell proliferation in vitro. Method:The chemical constituents were isolated and purified by silica gel，Sephadex LH-20，ODS column chromatography and semi-preparative high performance liquid chromatography （HPLC）.the structures were identified by spectroscopy methods such as NMR and MS，as well as analysis of physicochemical properties and/or comparison with literature data，and the inhibitory activities of 13 compounds on HepG2 and SMMC-7721 cells were measured by methyl thiazolyl tetrazolium （MTT） method. Result:Thirteen known compounds were isolated and identified from 90% ethanol extract of Corydalis impatiens as ethyl-5-hydroxy-2-pyridinecarboxylate（1），coryhumolide（2），3，4-cis-3，4-dihydroxy-β-ionone（3），megastigmane（4），9-hydroxy-4，7-megastigmadien-3-one（5），blumenol A（6），indole-3-carboxy acid（7），1-methyl-[1，2，4]triazolo[4，3-b][1，2，4]triazin-7-one （8），adenine（9），nicotinamide（10），2-hydroxymethyl-5-pyridinol（11），adenosine（12）， and β-daucosterol（13）. Cytotoxicities assay showed that the IC₅₀ value of compound 3 for the hepatic cell line HepG2 was 24.7 μmol·L^-1 （positive control drug cisplatin：4.8 μmol·L^-1），and IC₅₀ value of compound 4 for the hepatic cell line SMMC-7721 was 13.8 μmol·L^-1（positive control drug cisplatin：5.4 μmol·L^-1）. Conclusion:Compound 1 was a new natural compound，compounds 3-8 were obtained from genus Corydalis for the first time，and compounds 2，9-12 were isolated from this plant for the first time. Compound 3 exhibited weak inhibitory effect on hepatic cell line HepG2，and compound 4 exhibited moderate inhibitory effect on hepatic cell line SMMC-7721.The other compounds rest of ones exhibited no obvious inhibitory effect on hepatic cell line HepG2 or SMMC-7721.