Effects of Tibetan medicine Longdan zhike tablet on chronic obstructive pulmonary disease through MAPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Longdan zhike tablet (LDZK) is a Tibetan medicine formula commonly used in the highland region of Tibet, China, to ameliorate respiratory diseases, such as acute bronchitis and asthma. In Chinese traditional medicine, some herbal formulas with anti-inflammatory properties targeting the respiratory system are clinically adopted as supplementary therapies for chronic obstructive pulmonary disease (COPD). However, the specific anti-COPD effects of LDZK remain to be evaluated. AIM OF THE STUDY: The aim of this study is to identify the principal bioactive compounds in LDZK, and elucidate the effects and mechanisms of the LDZK on COPD. METHODS: High-resolution mass spectrometry was utilized for a comprehensive characterization of the chemical composition of LDZK. The therapeutic effects of LDZK were assessed on the LPS-papain-induced COPD mouse model, and LPS-induced activation model of A549 cells. The safety of LDZK was evaluated by orally administering a single dose of 30 g/kg to rats and monitoring physiological and biochemical indicators after a 14-day period. Network pharmacology and Western blot analysis were employed for mechanism prediction of LDZK. RESULTS: A comprehensive analysis identified a total of 45 compounds as the major constituents of LDZK. Oral administration of LDZK resulted in notable ameliorative effects in respiratory function, accompanied by reduced inflammatory cell counts and cytokine levels in the lungs of COPD mice. Acute toxicity tests demonstrated a favorable safety profile at a dose equivalent to 292 times the clinically prescribed dose. In vitro studies revealed that LDZK exhibited protective effects on A549 cells by mitigating LPS-induced cellular damage, reducing the release of NO, and downregulating the expression of iNOS, COX2, IL-1ß, IL-6, and TNF-α. Network pharmacology and Western blot analysis indicated that LDZK primarily modulated the MAPK signaling pathway and inhibited the phosphorylation of p38/ERK/JNK. CONCLUSIONS: LDZK exerts significant therapeutic effects on COPD through the regulation of the MAPK pathway, suggesting its potential as a promising adjunctive therapy for the treatment of chronic inflammation in COPD.

Evaluation of neoadjuvant immunotherapy and traditional neoadjuvant therapy for resectable esophageal cancer: a systematic review and single-arm and network meta-analysis.

Objective: This systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T]. Summary background data: NCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates. Results: We included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates. Conclusions: Among the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities. Systematic Review Registration: https://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.

Efficacy and Safety of Simultaneous Integrated Boost Intensity-Modulation Radiation Therapy Combined with Systematic and Standardized Management for Esophageal Cancer.

Objective: To analyze and compare the efficacy and safety of simultaneous integrated boost intensity-modulation radiation therapy (SIB-IMRT) combined with systematic and standardized management for esophageal cancer. Methods: From January 2012 to January 2019, 200 patients with esophageal cancer who received radical chemoradiotherapy in our hospital were treated with lymphatic drainage area radiation prevention combined with systematic and standardized management. According to difference in radiotherapy methods, the patients were divided into local lesion 92 patients treated with simultaneous integrated boost intensity-modulation radiation therapy (SIB-IMRT) combined with systematic standardized management (SIB-IMRT group), and late course boost intensity-modulation radiation therapy (LCB-IMRT) combined with systematic standardized management 108 patients (LCB-IMRT group). The short-term eficacy of the two groups were compared. The dose volume parameters of the organ in danger are evaluated based on the dose volume histogram. The related adverse reactions during chemoradiotherapy were compared between two groups. The local control rate and survival rate were compared between the two groups. Results: The recent total effective rates of rats in the SIB-IMRT group and LCB-IMRT group were 95.65% and 90.74%, respectively, and there was no significant difference between the two groups (p > 0.05). The mean doses to left and right lung, heart and spinal cord in the SIB-IMRT group were significantly lower than that in the LCB-IMRT group (p < 0.05). There was no significant difference in the incidence of adverse reactions such as radiation esophagitis, radiation pneumonitis, radiation tracheitis, gastrointestinal reaction and bone marrow suppression between the SIB-IMRT group and LCB-IMRT groups (p > 0.05). The one-year and three-year overall survival rates in the SIB-IMRT group and LCB-IMRT groups were 82.61%, 42.39% and 77.78%, 34.26%, respectively, and the median survival times were 38 and 29 months, respectively. The local control rates in the SIB-IMRT group and LCB-IMRT group in one and three years were 84.78%, 56.52% and 75.93%, 41.67%, respectively. The 3-year local control rate in the SIB-IMRT group was higher than that in the LCB-IMRT group (p < 0.05), but there was no significant difference in the 1-and 3-year overall survival rates between the two groups (p > 0.05). Conclusion: SIB-IMRT combined with systematic and standardized management in the treatment of esophageal cancer can reduce the amount of some organs at risk and improve the local control rate of the lesion.

Lymphedema complicated by protein-losing enteropathy with a 22q13.3 deletion and the potential role of CELSR1: A case report.

INTRODUCTION: 22q13.3 deletion syndrome is a well-known syndrome characterized by typical clinical findings including neonatal hypotonia, absent or severely delayed speech, intellectual disability, and other various features, and detection of a heterozygous deletion of chromosome 22q13.3 with the involvement of at least part of SHANK3. It is reported that 10% to 29% of patients with 22q13.3 deletion syndrome present lymphedema. Protein-losing enteropathy (PLE) has never been reported in 22q13.3 deletion syndrome. PATIENT CONCERNS: The patient presented to our institution for refractory hypoalbuminemia and chronic lymphedema in both legs. DIAGNOSIS: The patient manifested intellectual disability, absent speech, tooth grinding, dysmorphic face, and abnormal hands and toenails. Copy-number variation sequencing confirmed the maternal deletion in 22q13.31-q13.33 (chr22:46285592-51244566, hg19). The patient was genetically diagnosed with 22q13.3 deletion syndrome. INTERVENTIONS: Low-fat diets and medium-chain triglycerides supplements were prescribed. The patient was recommended to wear compression garments and elevate legs. OUTCOMES: The symptom of diarrhea was resolved, but hypoalbuminemia persisted. Lower extremities lymphedema was gradually becoming severe. CONCLUSIONS: Primary lymphedema and PLE can occur simultaneously in a patient with 22q13.3 deletion syndrome. The 2 phenotypes could share the same genetic etiology of congenital lymphatic abnormalities. CELSR1 deletion may play a role in lymphatic dysplasia. The case also provides additional proof of the pathogenic effect of CELSR1 on hereditary lymphedema.

Nutritional therapy and effect assessment of infants with primary intestinal lymphangiectasia: Case reports.

RATIONALE: Intestinal lymphangiectasia (IL) is a rare enteropathy involving the expansion and rupture of intestinal lymphatic channels. Although several reports have studied cases of primary IL (PIL), this condition is very rare, and is even less commonly encountered in infants. This study aimed to investigate the nutritional therapy and effect assessment of chylous reflux disorder caused by PIL in infants. PATIENT CONCERNS: Infantile patients were enrolled in the Affiliated Beijing Shijitan Hospital of the Capital Medical University between January 2012 and March 2014. The minimum age of onset was 4 months and the maximum age of onset was 16 months, with an average age of 4.9 months. DIAGNOSES: All children were inpatient who had been diagnosed with chylous reflux syndrome (chylothorax and/or chylic abdomen) caused by PIL. INTERVENTIONS: Retrospective analysis and individualized nutrition therapy of these cases were carried out. Finally, nutritional therapy and prognosis of PIL were assessed and summarized. OUTCOMES: All the children survived, showed improvement in the serum total protein, albumin, and HGB levels after nutritional therapy. After comprehensive nutritional therapy, we were able to achieve diarrhea control for all the 9 patients, and after treatment, the children passed soft, yellow stools 1 to 2 times/d. After treatment, the height and weight of all patients increased to within the normal ranges of the World Health Organization standard chart. The mean serum albumin level reached 41.3 g/L. All nutrition-related indicators were found to have significant improvement compared with the baseline levels. LESSONS: The results revealed that nutritional therapy for the 9 children with PIL was effective, and it may be able to improve the clinical syndromes and symptoms of children with PIL and promote recovery.

Discovery of a new structural class of competitive hDHODH inhibitors with in vitro and in vivo anti-inflammatory, immunosuppressive effects.

Human dihydroorotate dehydrogenase (hDHODH) is an inner mitochondrial membrane enzyme that involves in the fourth step of the biosynthesis of pyrimidine base. Inhibitors of hDHODH have been proven efficacy for the treatments of inflammation, rheumatoid arthritis, multiple sclerosis and cancer. In the present study, ascochlorin (ASC) and its derivatives, natural compounds from fungal metabolites, were discovered as hDHODH inhibitors by high-throughput screening. Enzyme kinetics studies showed that ASC competitively binds to hDHODH at the site of coenzyme Q substrate. In ex vivo study, ASC significantly inhibited the ConA-stimulated T lymphocytes proliferation and interleukin-2, interferon-γ production. Furthermore, ASC showed significant in vivo anti-inflammatory and immunosuppressive effects on the mice ears swelling, allogenic skin grafts and rat collagen-induced arthritis animal disease models. ASC significantly reduced ears edema level of mice, increased the survival time of allogenic skin implanted on the mice and attenuated arthritis severity of rat model. In conclusion, ASC was identified as a new structural class of hDHODH inhibitors with efficient anti-inflammatory, immunosuppressive activity, and may be a promising candidate for the development of new therapy in the treatment of autoimmune diseases.

Dynamic metabolic profiling of urine biomarkers in rats with alcohol­induced liver damage following treatment with Zhi­Zi­Da­Huang decoction.

Alcoholic liver disease (ALD) is a leading cause of liver­associated morbidity and mortality. Zhi­Zi­Da­Huang decoction (ZZDHD), a traditional Chinese medicine formula, has been frequently used to treat or alleviate the symptoms of the various stages of ALD. To identify metabolic changes and the ZZDHD mechanism of action on ALD, potential urine biomarkers involved in the effects of ZZDHD were identified. Additionally, dynamic metabolomic profiles were systematically analyzed using nuclear magnetic resonance (NMR) spectroscopy in conjunction with statistical analysis. Alcohol administration to experimental rats disrupted multiple metabolic pathways, including methionine, gut bacterial, energy and amino acid metabolism. However, ZZDHD relieved certain effects of alcohol on the metabolism and regulated changes in potential characteristic biomarkers, including dimethylglycine, hippurate, lactate and creatine. The present study investigated time­dependent metabolomic changes in the development of alcohol­induced liver injury, including the effect of ZZDHD intervention. These findings elucidated important information regarding the metabolic responses to the protective effects of ZZDHD. 1H NMR­based metabolomics method a reliable and useful tool for determining the metabolic progression of alcohol­induced liver injury and elucidating the underlying mechanisms of the effect of traditional Chinese medicine formulas. This study also demonstrated that NMR­based metabolomics approach is a powerful tool for understanding the molecular basis of pathogenesis and drug intervention processes.

Dosimetric and clinical predictors of radiation-induced lung toxicity in esophageal carcinoma.

AIMS AND BACKGROUND: Radiation-induced lung toxicity occurs frequently in patients with esophageal carcinoma. This study aims to evaluate the clinical and three-dimensional dosimetric parameters associated with lung toxicity after radiotherapy for esophageal carcinoma. METHODS AND STUDY DESIGN: The records of 56 patients treated for esophageal carcinoma were reviewed. The Radiation Therapy Oncology Group criteria for grading of lung toxicity were followed. Spearman's correlation test, the chi-square test and logistic regression analyses were used for statistical analysis. RESULTS: Ten of the 56 patients developed acute toxicity. The toxicity grades were grade 2 in 7 patients and grade 3 in 3 patients; none of the patients developed grade 4 or worse toxicity. One case of toxicity occurred during radiotherapy and 9 occurred 2 weeks to 3 months after radiotherapy. The median time was 2.0 months after radiotherapy. Fourteen patients developed late irradiated lung injury, 3 after 3.5 months, 7 after 9 months, and 4 after 14 months. Radiographic imaging demonstrated patchy consolidation (n = 5), atelectasis with parenchymal distortion (n = 6), and solid consolidation (n = 3). For acute toxicity, the irradiated esophageal volume, number of fields, and most dosimetric parameters were predictive. For late toxicity, chemotherapy combined with radiotherapy and other dosimetric parameters were predictive. No obvious association between the occurrence of acute and late injury was observed. CONCLUSIONS: The percent of lung tissue receiving at least 25 Gy (V25), the number of fields, and the irradiated length of the esophagus can be used as predictors of the risk of acute toxicity. Lungs V30, as well as chemotherapy combined with radiotherapy, are predictive of late lung injury.

Protective effect of a polysaccharide isolated from a cultivated Cordyceps mycelia on hydrogen peroxide-induced oxidative damage in PC12 cells.

Cordyceps sinensis as a well-known traditional Chinese tonic has many therapeutic functions. In the present study, an acid polysaccharide (APS) was isolated from cultivated Cordyceps mycelia by ion-exchange and sizing chromatography. The protective capacity of APS against H(2)O(2)-induced oxidative damage in rat pheochromocytoma PC12 cells was investigated by measuring cell viability, lactate dehydrogenase (LDH) release, antioxidant enzyme activity, malondialdehyde (MDA) levels and intracellular accumulation of reactive oxygen species (ROS) and Ca(2+). The results demonstrated that pretreatment of PC12 cells with APS, prior to H(2)O(2) exposure, significantly increased the survival of cells and the activities of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), and reduced the levels of LDH and MDA. Intracellular accumulation of reactive oxygen species (ROS) and Ca(2+) were also inhibited by APS treatment. In conclusion, APS was found to increase the cellular antioxidant defence capacity, thereby protecting PC12 cells against oxidative stress.

[Study on influence of glucoside Tripterygium total tablets on metabolism in rats by NMR metabonomic technique].

OBJECTIVE: To investigate the toxic effects of Glucoside Tripterygium total on rats with nuclear magnetic resonance (NMR)-based metabonomic method. METHOD: The influence of intragastric administration of Glucoside Tripterygium total suspension at two different doses on endogenetic metabolites in normal rat urine was determined with bio-NMR method then analyzed by pattern recognition technique and partial least-squares discriminant analysis (PLS-DA). Histopathological analysis was carried out. RESULT: Escalations of concentrations of urinary taurine, TMAO and glucose as well as reductions of concentrations of urinary citrate and 2-oxoglutarate were found by analysis of the 1H-NMR spectra, which was coincident with the result of histopathological analysis. The result of pathological examination indicated that pathologic change was not observed in nephridial tissue, but there were obvious changes in hepatic tissue. CONCLUSION: The urinary metabomic spectra were closely associated with the hepatic toxicity, which manifested the mitochondrial dysfunctions, the abnormal energy metabolism in TCA cycle as well as the abnormal glucose metabolism.

[Chemical constituents from fruits of Ligustrum lucidum].

OBJECTIVE: To study the chemical constituents from the fruits of Ligustrum lucidum. METHOD: The chemical constituents from the ethanol extract of L. lucidum were isolated and purified by silica gel, Sephadex LH-20, ODS column chromatographic methods. Their structures were identified on the basis of spectroscopic data and physico-chemical properties. RESULT: Twenty compounds were isolated and identified as oleanolic acid (1), crategolic acid (2), acetyl oleanolic acid (3), lupeol (4), betulin (5), dammarenediol-II (6), 3beta-acetyl-20, 25-epoxydammarane-24alpha-ol (7), 25-epoxydammarane-3beta, 24alpha-diol (8), dammar-24-ene-3beta-acetyl-20S-ol) (9), 20S, 24R-dammarane-25-ene-24-hydroperoxy-3beta, 20-diol (10), fouquierol (11), oliganthas A (12), dammarenediol II 3-O-palmitate (13), ocotillol II 3-O-palmitate (14), (E) -25-hydroperoxydammar-23-ene-3beta,20-diol (15), verbascoside (16), cimidahurinine (17), 2-(3,4-dihydroxyphenyl)-ethyl-O-beta-D-glucopyranoside (18), osmanthuside H (19), 2-(3,4-dihydroxyphenyl) ethanol (20). CONCLUSION: Compounds 4, 16,17, 19 were isolated from this plant for the first time, andcompounds 12-15 were isolated from this genus for the first time.

[Studies on chemical constituents from stems of Cudrania tricuspidata].

OBJECTIVE: To study the chemical constituents from the stems of Cudrania tricuspidata. METHOD: The chemical constituents from the ethanol extract of C. tricuspidata were isolated and purified by silica gel, Sephadex LH-20 column chromatographic methods. Their structures were identified on the basis of spectroscopic data and physico-chemical properties. RESULT: Thirteen compounds were isolated and identified as butyrospermyl acetate (1), glutinol (2), taraxerone (3), quercetin (4), kaempferol (5), isorhamnetin (6), orobol (7), 3'-O-methyorobol (8), taxifolin (9), naringenin (10), steppogenin (11), 1,3,6,7-tetrahydroxyx-anthone (12), 5,7-dihydroxy chromone (13). CONCLUSION: Compounds 1-3, 6, 13 were isolated from this genus for the first time, while compound 12 was isolated from this plant for the first time and we firstly reported the terpenoids from the genus Cudrania.

[Chemical constituents from stems of Lonicera japonica].

OBJECTIVE: To investigate the chemical constituents from the ethanol extract of the stems of Lonicera japonica. METHOD: The constituents were isolated and purified by repeated column chromatography on silica gel, Sephadex LH-20 and MCI HP-20. Their structures were identified by phsicochemical properties and spectroscopic analysis. RESULT: Thirteen compounds were isolated and identified as protocatechuic acid (1), caffeic acid (2), macranthoin G (3), esculetin (4), luteolin (5), quercetin (6), apigenin (7), luteolin-7-O-beta-D-glucopyranoside (8), isorhamnetin-7-O-beta-D-glucopyranoside (9), diosmetin-7-O-beta-D-glucopyranoside (10), rhoifolin (11), lonicerin (12), hydnocarpin D (13). CONCLUSION: Compound 4, 7, 9-11 were isolated from this plant for the first time, while compound 13 was first reported flavanolignan from this genus Lonicera.

[Chemical constituents from root barks of Periploca sepium].

OBJECTIVE: To investigate the chemical constituents of the root barks of Periploca sepium. METHOD: Column chromatographic techniques were used to isolate the chemical constituents. NMR and MS methods were employed for their structural elucidation. RESULT: Eight compounds were isolated and identified as isovanillin (1), vanillin (2), 4-methoxysalicylic acid (3), (24R)-9, 19-cycloart-25-ene-3beta, 24-diol (4), (24S)-9, 19-cycloart-25-ene-3beta, 24-diol (5), cycloeucalenol (6), beta-amyrin acetate (7) and alpha-amyrin (8). CONCLUSION: Compounds 1-6 were isolated from this plant for the first time.