OBJECTIVE: To investigate the clinical effect on functional dyspepsia differentiated as liver-stomach disharmony treated with acupoint application of Chinese herbal medicine and wax therapy on the basis of Professor TIAN Conghuo's theory, "regulating qi movement". METHODS: A total of 120 patients with functional dyspepsia of liver-stomach disharmony were randomly assigned to a combined therapy group (30 cases, 1 case dropped out), an acupoint application group (30 cases, 1 case dropped out), a wax therapy group (30 cases, 1 case dropped out) and a basic therapy group (30 cases, 2 cases dropped out). In the basic therapy group, omeprazole magnesium enteric-coated tablets were administered orally, 20 mg each time, once daily. Besides the treatment as the basic therapy group, the Chinese herbal acupoint application was used at Zhongwan (CV12) and Shenque (CV8) in the acupoint application group, and remained for 4 h in each intervention; and in the wax therapy group, wax therapy was delivered at the sites of Zhongwan (CV12) and Shenque (CV8) of the abdominal region and remained for 20 min in each intervention; and in the combined therapy group, the acupoint application was combined with wax therapy, administered once every other day or every two days, 3 times weekly. The duration of treatment was 4 weeks in the four groups. Before and after treatment, the score of main symptoms, the score of 36-item short-form health survey (SF-36) and the score of liver-stomach disharmony pattern were observed; and the clinical effect was evaluated in the four groups. RESULTS: After treatment, regarding main symptoms and liver-stomach disharmony pattern, the score of every item was lower than that before treatment in the 4 groups (P<0.01). The score for each dimension in SF-36 was higher than that before treatment in the combined therapy group and the acupoint application group (P<0.01, P<0.05). In the wax therapy group, the scores for physiological activities, bodily pain, general health, vitality, social activities and mental health in SF-36 were higher than those before treatment (P<0.01, P<0.05). In the basic therapy group, the scores for physiological performance, bodily pain, general health and mental health in SF-36 were higher than those before treatment (P<0.05, P<0.01). After treatment, in the combined therapy group, the score for gastric distension and discomforts was lower than those of the basic therapy group and the wax therapy group (P<0.01), and the scores for gastric fullness in the morning, pain in the upper abdominal region and burning sensation in the upper abdominal region, as well as the score for liver-stomach disharmony pattern were lower than those in the rest 3 groups (P<0.01, P<0.05). In the combined therapy group, the scores for physiological activities, physiological performance, and bodily pain were higher than those of the basic therapy group (P<0.01, P<0.05), the scores for physiological activities and bodily pain were higher when compared with those in the acupoint application group (P<0.01, P<0.05) and the scores for physiological activities and vitality were higher when compared with those in the wax therapy group (P<0.05). After treatment, the score for each item of main symptoms, the score for liver-stomach disharmony pattern in the acupoint application group, and the score for liver-stomach disharmony pattern in the wax therapy group were all lower in comparison with those in the basic therapy group (P<0.01, P<0.05). The total effective rates was 93.3% (28/30), 73.3% (22/30), 66.7% (20/30) and 50.0% (15/30) in the combined therapy group, the acupoint application group, the wax therapy group and the basic therapy group, respectively; and the total effective rate in the combined therapy group was superior to the other 3 groups (P<0.01); the total effective rates in the acupoint application group and the wax therapy group were higher than that in the basic therapy group (P<0.01). CONCLUSION The combination of acupoint application with Chinese herbal medicine and wax therapy, based on Professor TIAN Conghuo's theory of "regulating qi movement", can effectively treat functional dyspepsia, alleviate main symptoms and improve the quality of life in the patients.
Humans ; Acupuncture Points ; Dyspepsia/therapy* ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Adult ; Middle Aged ; Liver/drug effects* ; Combined Modality Therapy ; Stomach/drug effects* ; Young Adult ; Aged ; Waxes

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Cannabinoid is a kind of special compound in Cannabis sativa L., with a variety of biological activities, which have been widely used in medicine, food, cosmetics, textile, and other industries. However, Cannabis sativa contains the addictive ingredient Δ9-tetrahydrocannabinol, which also makes the application of Cannabis sativa subject to legal constraints. To prevent the abuse of Cannabis sativa related products and ensure the safety and effectiveness of products, it is very important to establish convenient, efficient, environmentally friendly, and inexpensive analytical methods that can be applied to the cannabinoid components in various matrices. Because of the high structural similarity, the poor stability of cannabinoid structure and the matrix effect in different matrices, the analysis becomes more complicated. At present, there is no unified standard for the quality control of cannabinoids, and there are various analytical methods. Based on the above questions, this paper introduces the classification of cannabinoids, expounds on the analysis methods of cannabinoids in Cannabis sativa plants, biological samples, food, cosmetics, and textiles, and looks forward to the future development direction of cannabinoid analysis methods, to provide useful help for the further development and rational application of Cannabis sativa .

Objective:To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) .Methods:This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate.Results:(1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference ( χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences ( P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions:Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

The blood-brain barrier in humans significantly restricts the effective delivery of drugs into the brain,resulting in poor therapeutic efficacy and difficulty in brain disease management.In recent years,innovative strategies and novel preparations have been studied and developed in order to circumvent the blood-brain barrier,achieve efficient drug entry into the brain,minimize the incidence of peripheral adverse effects,and bring significant therapeutic outcomes to patients.This review summarizes some key development strategies for treating encephalopathy,to provide some insights for the development of the next generation of drugs.

Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Background::Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US.Methods::The deaths, and mortality rates of asthma in China and the US during 1990–2019 were obtained from the Global Burden of Disease Study 2019. The age–period–cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated.Results::In 1990–2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively.Conclusions::In 1990–2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

BACKGROUND:Yougui Pill is a famous formula of the Chinese traditional medicine,which has good efficacy for lumbar disc herniation due to kidney yang insufficiency. OBJECTIVE:To investigate the potential targets and mechanism of action of Yougui Pill in the treatment of lumbar disc herniation by using network pharmacology and molecular docking technology,and verified by animal experiments. METHODS:(1)Network pharmacological analysis:We obtained the active ingredients and targets of Yougui Pill from TCMSP and other databases,collected genes related to lumbar disc herniation from GeneCards database,and took the intersection of the two for the topological analysis to derive the main active ingredients and core therapeutic targets.Gene ontology function analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using R software.(2)Molecular docking:Autodock and Pymol software were utilized for the prediction of molecular binding energy of TCM active ingredients to core therapeutic targets.(3)Animal experiments:Eighteen Sprague-Dawley rats were randomly divided into a control group,a degeneration group and a Yougui Pill group,with 6 rats in each group.A rat model of intervertebral disc degeneration was prepared by fiber puncture method in the degeneration and Yougui Pill groups.At 2 weeks after modeling,Yougui Pill was given by gavage in the Yougui Pill group,once a day for 2 consecutive weeks.The level of tumor necrosis factor-α in serum was detected by the ELISA method,and morphological changes of the annulus fibrosus and nucleus pulposus cells were observed using hematoxylin-eosin staining. RESULTS AND CONCLUSION:There were 90 active ingredients and 64 targets,and the main active ingredients were found to be quercetin,kaempferol,β-carotene,soybean flavonoid,and 4'-O-methylnyasol.The core targets of Yougui Pill for the treatment of lumbar disc herniation were interleukin 6,tumor necrosis factor-α,AKT1,interleukin 1B,and vascular endothelial growth factor A.Enrichment analysis revealed that the intersecting genes might be expressed through the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,MAPK signaling pathway,PI3K-AKT signaling pathway,and other signaling pathways to improve intervertebral disc degeneration.The molecular docking test verified that quercetin,kaempferol,and β-carotene had strong binding ability to the core targets.Animal experiments showed that the level of serum tumor necrosis factor α in the degeneration group was higher than that in the control group(P<0.05),and the level of serum tumor necrosis factor α in the Yougui Pill group was lower than that in the degeneration group(P<0.05).Hematoxylin-eosin staining showed that the fibrous annulus of the intervertebral discs and the structure of the nucleus pulposus in the degeneration group were destroyed,and the number of nucleus pulposus cells was reduced;there was a tendency to reconstructing the fibrous annulus of the intervertebral discs in the Yougui Pill group,and the number of nucleus pulposus cells increased compared with the degeneration group.To conclude,Yougui Pill may treat lumbar disc herniation by improving disc degeneration through the effects of quercetin,kaempferol,beta-carotene and other key active ingredients on core targets such as tumor necrosis factor.

Objective:To investigate the genomic profiles and immune microenvironment of olfactory neuroblastoma (ONB).Methods:Nineteen ONB cases diagnosed in the Beijing Tongren Hospital from May 2018 to October 2022 were divided into low-grade and high-grade groups according to the Hyams grading system, including 7 low-grade and 12 high-grade ONB. Whole exome sequencing and multiplex immunofluorescence analyses were performed on tissue samples of these ONB.Results:A total of 929 nonsynonymous alterations were identified in 18 of the 19 ONB (18/19) cases. The most commonly altered cancer-related genes were CTNNB1 (3/19) and ZNRF3 (3/19). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45/Mb, ranging from 0 to 3.25. The median tumor neoantigen load (TNB) was 9.39 neoantigens/Mb, ranging from 0 to 38.30. The median allelic mutation tumor heterogeneity (MATH) score was 16.95, ranging from 3.05 to 117.47. Only one of the 19 cases expressed PD-L1 (composite positive score, CPS>1) in the tumor cells. The median percentage of CD8 + tumor-infiltrating lymphocyte (TIL) in the tumor region was 1.08%. No significant differences were observed between the low-and high-grade groups for mutant genes, mutant pathways, TMB, TNB, MATH, PD-L1 expression levels, or CD8 + TILs percentage( P>0.05). However, the low-grade group showed significantly more CD68 + macrophages in both the tumor and total region than the high-grade group. Notably, CD68 +CD163 - macrophages accounted for an average of 80.52% of CD68 + macrophages. Conclusions:CTNNB1 and ZNRF3 are the most commonly altered cancer-related genes. The low expression of PD-L1 and the low percentage of CD8 + TIL indicate that ONB might not be sensitive to immunotherapy. The percentage of M1-type macrophages in low-grade ONB is significantly higher than that in high-grade ONB, suggesting that M1-type macrophages may be involved in the progression of ONB from low-grade to high-grade.