Mechanism Exploration of Euphorbia fischeriana Steud. for Liver Cancer Based on Aspartic Acid Identification in Metabolomics.

OBJECTIVE: To investigate the anti-liver cancer effects and aspartic acid (Asp)-related action mechanism of Euphorbia fischeriana Steud. (Lang Du, LD). METHODS: The mice model of liver cancer was established by injection of H22 cells. After 5 days, mice were randomly divided into model group, sorafenib group (20 mg/kg), LD high-dose (LDH, 1.36 g/kg) group, LD medium-dose (LDM, 0.68 g/kg) group, and LD low-dose (LDL, 0.34 g/kg) group, 10 mice each group. Drugs were intragastrically administered to the mice once daily for 10 days, respectively. Body weight, tumor size and tumor weight were recorded. Hepatic index was calculated. Pathological changes of liver cancer tissues were evaluated by hematoxylin and eosin staining and TUNEL staining. Liquid chromatography-mass spectrometer was used to analyze different metabolites between the model and LDH groups. RESULTS: After LD treatment, tumor weight, tumor size and hepatic index were reduced compared with the model group. Necrocytosis and karyorrhexis of tumor cells were found. Moreover, 61 differential metabolites (18 up-regulated, 43 down-regulated) were affirmed and 20 pathways of KEGG (P<0.05) were gotten. In addition, Bel-7402, HepG2 and H22 cell viabilities were significantly increased after adding Asp into the medium. And then, the cell proliferation effect induced by Asp was ameliorated by LD. CONCLUSION: The anti-liver cancer efficacy of LD extract was validated in H22 mice model, and inhibition of Asp level might be the underlying mechanism.

Acylhydrazone-derived whole pectin-based hydrogel as an injectable drug delivery system.

Injectable hydrogel-based drug delivery systems have attracted more and more attention due to their sustained-release performance, biocompatibility, and 3D network. The present study showed whole pectin-based hydrogel as an injectable drug delivery system, which was developed from oxidized pectin (OP) and diacylhydrazine adipate-functionalized pectin (Pec-ADH) via acylhydrazone linkage. The as-prepared hydrogels were characterized by 1H NMR, FT-IR, and SEM techniques. The equilibrium swelling ratio of obtained hydrogel (i.e., sample gel 5) was up to 4306.65 % in the distilled water, which was higher than that in PBS with different pH values. Increasing the pH of the swelling media, the swelling ratio of all hydrogels decreased significantly. The results that involved the swelling properties indicated the salt- and pH-responsiveness of the as-prepared hydrogels. The drug release study presented that 5-FU can be persistently released for more than 12 h without sudden release. Moreover, the whole pectin-based hydrogel presented high cytocompatibility toward L929 cell lines, and the drug delivery system showed a high inhibitory effect on MCF-7 cell lines. All these results manifested that the acylhydrazone-derived whole pectin-based hydrogel was an excellent candidate for injectable drug delivery systems.

Tribulus terrestris L. induces cell apoptosis of breast cancer by regulating sphingolipid metabolism signaling pathways.

BACKGROUND: Tribulus terrestris L. (TT) was initially documented in Shen-Nong-Ben-Cao-Jing and has been used for thousands of years in China as a herb to calm liver, dispel melancholy and wind, promote blood circulation, improve eyesight, and relieve itching. Moreover, it was also used to treat breast cancer in ancient China. However, the pharmacological activities of TT extract on breast cancer have received little attention. PURPOSE: In this study, we investigated the anti-breast cancer effects and possible mechanisms of action of this herbal drug. METHODS: Network pharmacology analysis the study of network pharmacology was done to analyze the possibility of TT's anti-breast cancer effect. And then, molecular docking between TT7/TT8 and vascular endothelial growth factor receptor 2 (VEGFR2) were performed by Autodock software as well as the related protein expressions were analyzed by western blot to verify this effect. In vivo experiment: The mouse model of breast cancer was established by injection of 4T1 cells. Then drugs were intragastrically administered to the mice once daily for fourteen days. Body weight, tumor size, and tumor weight were recorded at the end of the experiment. Moreover, tumor inhibitory rate was calculated. Finally, pathological changes and apoptosis of breast cancer tissues were respectively evaluated by HE and Hoechst staining. Proteomics and metabonomics analyses: The tumor tissues were chosen to perform conjoint analysis. Firstly, differential proteins and metabolites were found. Furthermore, the functional analyses of them were analyzed by software. At the last, immunofluorescent staining of SGPP1, SPHK1 and p-SPHK1 in tumor tissue were done. RESULTS: 12 active ingredients of TT, 127 targets of active ingredients, 15,253 targets of breast cancer, 1,225 targets of Ru yan, and 123 overlapping genes were obtained in the network pharmacology study. There was firm conjunction between TT7/TT8 and VEGFR2. Besides, tumor size and weight were markedly reduced in TT groups compared to the model group. The tumor inhibitory rate was more than 26% in TTM group. After drug treatment, many adipocytes and cracks between tumor and apoptosis were discovered. The western blot results showed that TT aqueous extract lowered the levels of VEGFR2, ERK1/2, p-ERK1/2 (Thr202, Tyr204) and Bcl2, while increasing the levels of Bax and the ratio of Bax/Bcl2. Furthermore, 495 differential proteins and 76 differential metabolites were found between TTM and model groups with the sphingolipid metabolism pathway being enriched. At last, TT treatment significantly reduced the levels of SGPP1, SPHK1 and p-SPHK1 in tumor tissue. CONCLUSIONS: In conclusion, TT demonstrates therapeutic effects in a mouse model of breast cancer, and its mechanism of action involves the regulations of sphingolipid metabolism signaling pathways. This study lends credence to the pharmacological potential of TT extract as a breast cancer therapy.

Promoting liver cancer cell apoptosis effect of Tribulus terrestris L. via reducing sphingosine level was confirmed by network pharmacology with metabolomics.

Background: Tribulus terrestris L. (TT) is one of the most common Chinese herbs and distributes in various regions in China. TT was first documented to treat breast cancer in Shen-Nong-Ben-Cao-Jing. However, the pharmacological activities of TT extract on liver cancer have not been reported. In this study, we investigated its anti-liver cancer activity and underlying mechanism. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases were used to obtain the active ingredients and the targets of TT. Genecards database was employed to acquire TT targets in liver cancer. Furthermore, Venny 2.1, Cytoscape 3.8.2, DAVID 6.8 software were utilized to analyze the relationship between TT and liver cancer. In vivo experiment: The animal model of liver cancer was established by injection of H22 cells into Balb/c mice. After five days, drugs were intragastrically administered to the mice daily for 10 days. Body weight, tumor size and tumor weight were recorded. Tumor inhibitory rate was calculated. Protein levels were examined by Western blotting. Pathological changes of liver cancer tissues were evaluated by HE and Tunel staining. Metabolomics study: LC-MS was used to analyze different metabolites between model and TTM groups. Results: 12 active ingredients of TT, 127 targets of active ingredients, 17,378 targets of liver cancer, and 125 overlapping genes were obtained. And then, 118 items of GO biological processes (BP), 54 items of GO molecular function (MF), 35 items of GO cellular component (CC) and 128 pathways of KEGG were gotten (P < 0.05). Moreover, 47 differential metabolites were affirmed and 66 pathways of KEGG (P < 0.05) were obtained. In addition, after TT and sorafenib treatment, tumor size was markedly reduced, respectively, compared with model group. Tumor weight was significantly decreased and tumor inhibitory rate was more than 44% in TTM group. After TT treatment, many adipocytes, cracks between tumor cells and apoptosis were found. The levels of pro-Cathepsin B, Cathepsin B, Bax, Bax/Bcl2, Caspase3 and Caspase7 were markedly increased, but the level of Bcl2 was significantly reduced after TT treatment. Conclusion: TT has a broad range of effects on various signaling pathways and biological processes, including the regulation of apoptosis. It exhibits antitumor activity in an animal model of liver cancer and activates the apoptotic pathway by decreasing Sph level. This study provides valuable information regarding the potential use of TT extract in the treatment of liver cancer and highlights the importance of investigating the underlying molecular mechanisms of traditional medicines for the development of new therapeutic drugs in liver cancer.

Identification of predictors of long-term survival and prognostic outcomes in thymic squamous cell carcinoma: A real-world study.

BACKGROUND: Although thymic squamous cell carcinoma (TSCC) is among the most prevalent forms of thymic carcinoma, there are relatively few studies on this tumor type, and its staging, optimal treatment strategies, and relevant prognostic factors remain controversial. METHODS: The present study analyzed 79 patients diagnosed with TSCC between January 2008 and January 2021. Kaplan-Meier curves and Cox univariate and multivariate regression analyses were used to explore factors associated with overall survival (OS) and progression-free survival (PFS) in the overall patient cohort and patient subgroups stratified according to the TNM stage. Time-dependent receiver operating characteristic (ROC) analyses were used to compare the TNM and Masaoka systems as predictors of patient prognosis. RESULTS: The 5- and 10-year OS rates in this study were 65.5% and 49.4%, respectively, with corresponding 5- and 10-year PFS rates of 52.3% and 37.9%. Survival outcomes were better for patients with early-stage disease (p < 0.001) and patients that underwent surgical treatment (p < 0.001). Neither extent of resection (p = 0.820) nor the surgical approach (p = 0.444) influenced patient survival. In individuals with advanced disease, all forms of adjuvant therapy including radiotherapy (p = 0.021), chemotherapy (p = 0.035), and chemoradiation (p = 0.01) significantly improved patient PFS, but only adjuvant chemoradiotherapy improved patient OS (p = 0.035). When predicting the patient survival outcomes, the TNM system was slightly superior to the Masaoka system (area under the ROC curve [AUC] at 5 years: OS, 0.742 vs. 0.723; PFS, 0.846 vs. 0.816). CONCLUSION: TSCC is an orphan malignancy with a poor prognosis. TNM staging may be superior to Masaoka staging as a predictor of TSCC patient prognosis. Surgery is the mainstay of TSCC treatment. Video-assisted thoracoscopy (VATS) should be considered for selected patients. Multimodal therapy was associated with excellent results for patients with advanced TNM stage, particularly when surgery was accompanied by adjuvant chemoradiation.

The deficiency of Maged1 attenuates Parkinson's disease progression in mice.

Melanoma-associated antigen D1 (Maged1) has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, and drug addiction. However, the role of Maged1 in Parkinson's disease (PD) remains unclear. In this study, we observed that Maged1 was expressed in the dopaminergic (DA) neurons of the substantia nigra in mice and humans, which could be upregulated by the in vivo or in vitro treatment with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-Methyl-4-phenylpyridinium iodide (MPP+). Genetic ablation of Maged1 in mice attenuated motor deficits, the loss of DA neurons, and disease progression induced by MPTP. Moreover, Maged1 deficiency protected DA neurons against MPP+-induced toxicity in primary cultured cells. Mechanistically, loss of Maged1 upregulated the Akt signaling pathway and downregulated the mTOR signaling pathway in SH-SY5Y cells, which may in turn attenuate the cell apoptosis and impairment of autophagy. Consistent with it, the degeneration of midbrain and striatum among elderly Maged1 knockout mice was relatively mild compared to those in wild-type mice under physiological conditions. Taken together, this study suggested that Maged1 deficiency inhibited apoptosis and enhanced autophagy, which may provide a new potential target for the therapy of PD.

Novel strategies to reverse chemoresistance in colorectal cancer.

Colorectal cancer (CRC) is a common gastrointestinal malignancy with high morbidity and fatality. Chemotherapy, as traditional therapy for CRC, has exerted well antitumor effect and greatly improved the survival of CRC patients. Nevertheless, chemoresistance is one of the major problems during chemotherapy for CRC and significantly limits the efficacy of the treatment and influences the prognosis of patients. To overcome chemoresistance in CRC, many strategies are being investigated. Here, we review the common and novel measures to combat the resistance, including drug repurposing (nonsteroidal anti-inflammatory drugs, metformin, dichloroacetate, enalapril, ivermectin, bazedoxifene, melatonin, and S-adenosylmethionine), gene therapy (ribozymes, RNAi, CRISPR/Cas9, epigenetic therapy, antisense oligonucleotides, and noncoding RNAs), protein inhibitor (EFGR inhibitor, S1PR2 inhibitor, and DNA methyltransferase inhibitor), natural herbal compounds (polyphenols, terpenoids, quinones, alkaloids, and sterols), new drug delivery system (nanocarriers, liposomes, exosomes, and hydrogels), and combination therapy. These common or novel strategies for the reversal of chemoresistance promise to improve the treatment of CRC.

Peripheral Treg Levels and Transforming Growth Factor-ß (TGFß) in Patients with Psoriatic Arthritis: A Systematic Review Meta-Analysis.

INTRODUCTION: Studies on the level of regulatory T (Treg) cells in psoriatic arthritis (PsA) have been controversial, leading to disagreement regarding the role Treg cells play in the pathogenesis of the disease. To clarify the status of Treg cells in patients with PsA, we performed a meta-analysis to determine the levels of Treg cells and serum Treg-associated cytokines in PsA patients. METHODS: According to published data from PubMed, Web of Science, Embase, Clinical Trials.gov, MEDLINE, Web of Knowledge, Cochrane Library, and FDA.gov, we determined the Treg and Treg cytokine levels in patients with PsA. The effect estimates were pooled using a random-effects model. RESULTS: This meta-analysis included 12 studies. Compared to healthy controls (HCs), the proportions of Treg cells had no significant difference in patients with PsA (based on standardized means[SMD] = - 1.038, 95% confidence intervals[CI] = - 2.165 to 0.089, p = 0.071). On the basis of subgroup analysis, patients with PsA had a lower percentage of CD4+ Treg cells (SMD = - 1.501, 95% CI - 2.799 to - 0.202, p = 0.023) than OKT8+ Treg (SMD = 0.568, 95% CI - 2.127 to 3.263, p = 0.679). Besides, CD4+CD25+FoxP3+ Treg cells and CD4+CD25highCD127low Treg cells were both significantly decreased on the levels of PBMCs in patients with PsA (SMD = - 0.764, 95% CI - 1.404 to - 0.125, p = 0.019; SMD = - 5.184, 95% CI - 6.955 to - 3.412, p < 0.001). CD4+CD25+FoxP3+ Treg cells were particularly more abundant in the synovial fluid thanin peripheral blood (SMD = 3.288, 95% CI 2.127 to 4.449, p < 0.001). No significant difference was observed in the proportion of CD4+CD25+ Treg cells in peripheral blood and CD4+CD25+FoxP3+ Treg cells in CD4+ T cells (SMD = - 2.498, 95% CI - 7.720 to 2.725, p = 0.349; SMD = - 0.719, 95% CI - 2.525 to 1.086, p = 0.435). PsA patients had decreased cytokines such as transforming growth factor-ß (TGFß) (SMD = - 2.199, 95% CI - 3.650 to - 0.749, p = 0.003). CONCLUSIONS: Treg definition markers influence the scale of Treg cells in patients with PsA. Pathogenesis of PsA may be attributed to an insufficient or malfunctioning Treg population.

Metastatic lymph nodes and prognosis assessed by the number of retrieved lymph nodes in gastric cancer.

BACKGROUND: The prognostic value of quantitative assessments of the number of retrieved lymph nodes (RLNs) in gastric cancer (GC) patients needs further study. AIM: To discuss how to obtain a more accurate count of metastatic lymph nodes (MLNs) based on RLNs in different pT stages and then to evaluate patient prognosis. METHODS: This study retrospectively analyzed patients who underwent GC radical surgery and D2/D2+ LN dissection at the Cancer Hospital of Harbin Medical University from January 2011 to May 2017. Locally weighted smoothing was used to analyze the relationship between RLNs and the number of MLNs. Restricted cubic splines were used to analyze the relationship between RLNs and hazard ratios (HRs), and X-tile was used to determine the optimal cutoff value for RLNs. Patient survival was analyzed with the Kaplan-Meier method and log-rank test. Finally, HRs and 95% confidence intervals were calculated using Cox proportional hazards models to analyze independent risk factors associated with patient outcomes. RESULTS: A total of 4968 patients were included in the training cohort, and 11154 patients were included in the validation cohort. The smooth curve showed that the number of MLNs increased with an increasing number of RLNs, and a nonlinear relationship between RLNs and HRs was observed. X-tile analysis showed that the optimal number of RLNs for pT1-pT4 stage GC patients was 26, 31, 39, and 45, respectively. A greater number of RLNs can reduce the risk of death in patients with pT1, pT2, and pT4 stage cancers but may not reduce the risk of death in patients with pT3 stage cancer. Multivariate analysis showed that RLNs were an independent risk factor associated with the prognosis of patients with pT1-pT4 stage cancer (P = 0.044, P = 0.037, P = 0.003, P < 0.001). CONCLUSION: A greater number of RLNs may not benefit the survival of patients with pT3 stage disease but can benefit the survival of patients with pT1, pT2, and pT4 stage disease. For the pT1, pT2, and pT4 stages, it is recommended to retrieve 26, 31 and 45 LNs, respectively.

Mucosa-associated lymphoid tissue lymphoma in thymus: a SEER analysis.

OBJECTIVES: The present study explores an extremely rare disease, thymic mucosa-associated lymphoid tissue (MALT) lymphoma, for its characteristics and prognostic factors by analyzing the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: From 2000 to 2018, cases with a diagnosed thymic MALT lymphoma were extracted. Clinical characteristics, treatments, and survival patterns of these cases were analyzed. RESULTS: Thymic MALT lymphoma (n = 26) accounted for 0.09% of all MALT lymphomas. With a sex ratio of 0.53 (male/female), 68% white population was affected. Most cases were diagnosed with Ann Arbor stage I (50%), yet advanced-stage did not show worse prognosis (p = 0.236). Different treatment protocols did not influence the overall prognosis (p > 0.99). The 5- and 10- year overall survival rates were 83.1% and 78.2%, respectively. Older than 70 years may be an independent risk factor for overall survival (HR = 7.166 [95% CI 1.173-43.756], p = 0.033). CONCLUSION: Thymic MALT lymphoma is a highly rare disease with a favorable prognosis. Ann Arbor staging might not be appropriate to classify severity of this disease or its treatment. Older people may have worse survival. A standardized treatment mode needs to be established, and surgery could remain as the mainstay.

[Clinical Characteristics of 30-day Unplanned Reoperations after Thoracic Surgery].

Objective To investigate the clinical characteristics of 30-day unplanned reoperations after thoracic surgery. Methods We retrospectively analyzed the clinical data of patients with unplanned reoperations within 30 days after thoracic surgery in Peking Union Medical College Hospital from May 2016 to May 2021. Results The 30-day unplanned reoperations showed the incidence of 0.75%(79/10 543),the median hospital stay of 19(12,37) days,and the median hospitalization cost of 109 929.11(80 549.46,173 491.87) yuan.Twenty-two(27.85%) patients received blood transfusion and 26(32.91%) underwent intensive care.The period between May 2016 and May 2017 witnessed the most unplanned reoperations.The main causes of unplanned reoperations after thoracic surgery were bleeding(21.52%),chylothorax(17.72%),pulmonary air leakage(16.46%),atelectasis(13.92%),and gastroesophageal fistula(11.39%).Specifically,the main causes of unplanned reoperations in the patients of non-esophagus/cardia group were bleeding,pulmonary air leakage,atelectasis,and chylothorax,and those in the patients of esophagus/cardia group were gastroesophageal fistula,incision infection and poor healing,bleeding,and chylothorax.Among all the patients with unplanned reoperations,4 patients died,17 improved,and 58 recovered. Conclusions The patients who underwent unplanned reoperations after thoracic surgery had a long hospital stay and high hospitalization costs. Bleeding,chylothorax,pulmonary air leakage,atelectasis,and gastroesophageal fistula were the main reasons for the unplanned reoperations.

Pt@Tetraphenyl-1,3-butadiene Nanocrystals with Coreaction Acceleration and Crystallization-Induced Enhanced Electrochemiluminescence for Ultrasensitive MicroRNA Detection.

Herein, Pt@tetraphenyl-1,3-butadiene nanocrystals (Pt@TPB NCs) with high electrochemiluminescence (ECL) efficiencies as ECL emitters were developed to construct an ultrasensitive biosensing platform for the detection of microRNA-21 (miRNA-21). Interestingly, Pt@TPB NCs not only exhibited high carrier densities and electron mobilities to achieve efficient electron-hole pair recombinations for high ECL emission but also served as coreaction accelerators of endogenous coreactant-dissolved O2 with good electrocatalytic activities to produce abundant reactive oxygen species (ROS) for facilitating the interactions between TPB NCs and ROS, which further obtain intense ECL emission. Impressively, Pt@TPB NCs with dissolved O2 as coreactants displayed high ECL efficiencies (ΦECL) of 7.83, taking the ΦECL of Ru(bpy)32+/dissolved O2 ECL system as 1. Herein, Pt@TPB NCs with strong ECL signals were used as ECL emitters to combine target-induced DNA walker amplification with high conversion efficiency for the construction of an ultrasensitive ECL biosening platform which accomplished microRNA-21 detection with a low detection limit of 83.8 aM. Therefore, the developed synergy effects in Pt@TPB NCs are expected to guide the progress of highly efficient ECL emitters for sensing analysis and disease diagnosis.

A systematic review and meta-analysis of thymic mucosa-associated lymphoid tissue lymphoma.

Background: Mucosa-associated lymphoid tissue (MALT) lymphoma of the thymus is a rare disease. The present meta-analysis aims at accumulating current evidence to explore the clinical characteristics, treatments, and prognoses of thymic MALT lymphoma. Methods: We searched seven databases for studies published between the start date of database establishment and September 15, 2021. We included studies of patients with histological diagnoses and excluded those without data specifically on thymic MALT lymphoma. The quality was analyzed using an assessment tool. All data were tabulated. Pooled proportion was obtained using random-effects model. Statistical analysis was performed on R statistic software. Results: Overall, 52 case reports and 13 case series were eligible. The quality of case reports was inferior to that of case series in terms of selection (P<0.001). Based on the analysis of patients in the case reports, age, gender, concurrent diseases, and tumor size did not differ between limited-stage and advanced-stage cases. Surgery is the mainstay to treat thymic MALT lymphoma. The surgical approach and extent did not influence the occurrence of events. Patients at Ann Arbor stage I were prone to not receiving postoperative therapy (P=0.011), though it may not reduce the occurrence of events (P=0.637). The five-year overall survival (OS) rate and five-year progression-free survival (PFS) rate were 97.2% and 88.4%, respectively. Patients with advanced-stage disease were more likely to suffer events (P=0.009). Conclusions: Thymic MALT lymphoma is an extremely rare disease with a favorable prognosis. Currently available evidence is insufficient to draw solid judgments about treatment and prognosis. However, patients may benefit if thymectomy is chosen as the primary treatment. In some patients, lymph node sampling or dissection should be considered. In addition, if the patient is at an advanced-stage, postoperative therapy should be considered.

Surgical Treatment of Ectopic Mediastinal Parathyroid Tumors: A 23-Year Clinical Data Study in a Single Center.

Background. Ectopic mediastinal parathyroid glands are parathyroid glands located completely below the clavicle. At present, most literature reports on ectopic mediastinal parathyroid tumors (EMPT) are case reports or small case sequences.Methods. This study conducted a retrospective analysis of ectopic mediastinal parathyroid tumors cases treated over the past 23 years, summarizing and analyzing general conditions, preoperative positioning, postoperative pathology, intraoperative conditions, and long-term follow-up results.Results. This study enrolled 28 patients. Among them, 27 patients underwent preoperative localization diagnosis using 99mTc-sestamibi scan (MIBI) in conjunction with chest computed tomography (CT), including 26 cases of the anterior superior mediastinum and 2 cases of middle mediastinum. Postoperative pathology revealed 23 cases of parathyroid adenoma, 4 cases of parathyroid hyperplasia, and 1 case of parathyroid cyst. In this study, 12 patients underwent video-assisted thoracoscopic surgery (VATS) and thoracotomy approaches. Using Mann-Whitney U test, we discovered that VATS approach group is significantly superior in surgical time (P = 0.039) and intraoperative bleeding (P < 0.001). Within one week of surgery, 26 patients with primary hyperparathyroidism (PHPT) experienced a significant decrease in blood parathyroid hormone (PTH) (P < 0.001) and blood calcium (P < 0.001), and all achieved long-term remission.Conclusions. EMPT is most frequently performed in the anterior superior mediastinum. EMPT is predominantly parathyroid tumors, and most of them are associated with PHPT. MIBI and chest CT combination can be used for preoperative lesion localization (positive rate 96.15%). VATS can be used as a better surgical approach. PHPT patients before surgery can achieve long-term symptom relief with surgical treatment.

Use of Buried Guide Needle to Fix Inferior Eyelid Orbital Septum Fat for Tear Trough Depression Filling.

ABSTRACT: Fat fixation is a key step in filling tear trough depression with inferior eyelid orbital septum fat. The ideal position for inferior eyelid fat fixation is to cross the tear trough ligament causing tear trough depression and the orbicularis retaining ligament, with the distal end fixed at the farthest end of the dissected lacuna deep down the inferior orbicularis oculi muscle. Traditional suturing is difficult in the deep narrow lacunae, but a buried guide needle can be used to suture and fix the fat in the deepest lacuna. In this study, 264 patients who underwent tear trough filling using a buried guide needle to fix the released inferior eyelid orbital septum fat from 2017 to 2020 were followed up. The preoperative and postoperative imaging findings were compared to evaluate the effectiveness of the operation and postoperative complications. The inferior eyelid bulging, loose skin, and tear trough depression significantly improved than that before the operation. None of the patients had any severe complications, such as inferior eyelid ectropion, lagophthalmos, scar hyperplasia, and diplopia, in the long term (6 months) postoperatively. Five patients showed mild eyelid-eyeball separation and recovered in 1 month. Four patients had diplopia, and 3 patients had chemosis; all recovered in 7 days. The tear trough depression was not corrected completely in 2 patients. The operation showed satisfactory results in the improvement of tear trough depression in addition to alleviation of inferior eyelid bulging and loose inferior eyelid skin that is caused by the traditional inferior eyelid pouch removal.

Exploring the Effects of Magnesium Deficiency on the Quality Constituents of Hydroponic-Cultivated Tea (Camellia sinensis L.) Leaves.

Magnesium (Mg) plays important roles in photosynthesis, sucrose partitioning, and biomass allocation in plants. However, the specific mechanisms of tea plant response to Mg deficiency remain unclear. In this study, we investigated the effects of Mg deficiency on the quality constituents of tea leaves. Our results showed that the short-term (7 days) Mg deficiency partially elevated the concentrations of polyphenols, free amino acids, and caffeine but decreased the contents of chlorophyll and Mg. However, long-term (30 days) Mg-deficient tea displayed decreased contents of these constituents. Particularly, Mg deficiency increased the index of catechins' bitter taste and the ratio of total polyphenols to total free amino acids. Moreover, the transcription of key genes involved in the biosynthesis of flavonoid, caffeine, and theanine was differentially affected by Mg deficiency. Additionally, short-term Mg deficiency induced global transcriptome change in tea leaves, in which a total of 2522 differentially expressed genes were identified involved in secondary metabolism, amino acid metabolism, and chlorophyll metabolism. These results may help to elucidate why short-term Mg deficiency partially improves the quality constituents of tea, while long-term Mg-deficient tea may taste more bitter, more astringent, and less umami.

Silencing of circ_0000517 suppresses proliferation, glycolysis, and glutamine decomposition of non-small cell lung cancer by modulating miR-330-5p/YY1 signal pathway.

In recent years, circular RNA (circRNA) has been found to be involved in a variety of cancer processes. More and more attention has been paid to the research of circRNA in lung cancer. This study aims to investigate whether circ_0000517 affected the physiology of non-small cell lung cancer (NSCLC) and the underlying mechanism. The results demonstrated that circ_0000517 was highly expressed in lung cancer tissues and cells, and overexpression of circ_0000517 was negatively correlated with the prognosis of NSCLC patients. Silencing of circ_0000517 significantly inhibited the proliferation, glycolysis, and glutamine decomposition of NSCLC cells in vitro and repressed the growth of xenografted tumors in vivo. Moreover, knockdown of circ_0000517 attenuated the expression of PCNA, HK2, LDHA, ASCT2, and GLS1. Further study found that circ_0000517 targeted miR-330-5p and miR-330-5p targeted YY1. In addition, miR-330-5p inhibitor reversed inhibition of cancer cell proliferation, glycolysis, and glutamine decomposition induced by si-circ_0000517. In conclusion, our study revealed that silencing of circ_0000517 improved the progression of NSCLC through regulating miR-330-5p/YY1 axis.

Cough Inhibition Activity of Schisandra chinensis in Guinea Pigs.

Chronic cough is very common in respiratory clinics, and no effective drugs are available. Schisandra chinensis (Turcz.) Baill. (S. chinensis), an important traditional Chinese medicine, has been extensively prescribed for patients with a persistent cough. Preliminary research indicated that 95% ethanol extracts (EE) of S. chinensis showed remarkable antitussive activity in guinea pigs exposed to cigarette smoke (CS). To find out the antitussive ingredients of S. chinensis, EE was divided into four fractions according to the polarity: petroleum ether extract (PEE), ethyl acetate extract (ECE), n-butyl alcohol extract, and residue extract. The antitussive, antioxidant, and anti-inflammatory effects of the four fractions were evaluated in a guinea pig model of cough hypersensitivity induced by CS exposure. Eighteen main constituents of the two effective fractions, PEE and ECE, were identified using ultra-high-pressure liquid chromatography electronic spray ion time-of-flight mass spectrometry. The cough inhibition activities of compound 1, 3, 9, 10, 17 were evaluated on citric acid induced acute cough guinea pigs. The results showed that the antitussive activity of EE was almost all contained in PEE and ECE. The 16 major peaks in PEE were identified as 15 lignans (1-12 and 14-16) and 1 triterpene (compound 13), and 3 major peaks (1, 17, and 18) in ECE were also identified as lignans. Three doses of five compounds brought about a significant decrease in number of cough efforts (P < .01), and the cough inhibition rates were between 40.9% and 85.1%. Therefore, lignans are the antitussive ingredients of S. chinensis.

Paeoniflorin elicits the anti-proliferative effects on glioma cell via targeting translocator protein 18 KDa.

As a natural compound isolated from Paeoniae radix, Paeoniflorin (PF) has been shown the antitumor effects in various types of human cancers including glioma, which is one of the serious tumors in central nervous system. Translocator protein 18 KDa (TSPO) has been shown to be relevant to the glioma aetiology. However, the regulation of PF in TSPO and neurosteriods biosynthesis on glioma is still unclear. In the present study, the glioma cell (U87 and U251) were cultured and used to quantify the bindings of PF on TSPO. Results indicated that there was not significant different between IC50 of PF and TSPO ligand PK11195. Moreover, PF exerted the anti-proliferative effects in glioma cell with a dose dependent inhibition from 12.5 to 100 µM in vitro. Consistent with the effects of PK11195, lowered levels on progesterone, allopregnanolone, as well as TSPO mRNA were induced by PF (25 and 50 µM). Furthermore, a xenograft mouse model with U87 cell-derived was significant inhibited by PF treatment, as well as the PK11195 administration. These results demonstrate that PF exerts its antitumor effects associated with the TSPO and neurosteroids biosynthesis in glioma cells could be a promising therapeutic agent for glioma therapy.

A study on the Fe3O4@Fructus mori L. polysaccharide particles with enhanced antioxidant activity and bioavailability.

Molecular conformation is closely related to the functional properties of macromolecules. In order to prove that the bioactivity of mulberry fruit polysaccharides (MFPs) is greatly affected by the conformation, and to improve adsorption properties, we have designed Fe3O4@MFPNPs core-shell nanoparticles. The spherical Fe3O4@MFPNPs have been successfully synthesized with particle size distribution in the ranges of 3-10 nm and 68-164 nm, which are smaller than their previously prepared original polysaccharides and MFP-Fe(iii). The Fe3O4@MFPNPs showed better antioxidant activity in comparison to MFP and MFP-Fe(iii). The difference in the antioxidant activity between Fe3O4@MFPNPs and MFP-Fe(iii), both of which were modified based on elemental iron, may be attributed to their different conformations: MFP-Fe(iii) were rod-shaped, while Fe3O4@MFPNPs were spherical. Furthermore, Fe3O4@MFPNPs also exhibited greater absorption in the small intestine, which can promote its application in human health.