The 2-(2-phenylethyl)chromones were separated from agarwood of Aquilaria agallocha Roxb. and their anti-KRAS mutant non-small cell lung cancer (NSCLC) activities were evaluated. 2-(2-Phenyethyl)chromones in agarwood were separated and purified by silica gel, RP-18 reverse phase silica gel, MCI gel CH20P, Diol, and semi preparative HPLC chromatography techniques, while the structures of the compounds were identified by extensive spectroscopic analysis, such as 1D and 2D NMR and ESI-MS. The cell counting kit 8 (CCK-8) assay was used to screen the anti-tumor activity of the isolated monomeric compounds on three KRAS-mutant NSCLC cells. The cell proliferation, cloning formation, adhesion ability, and cell cycle arrest activity of compound 8 were analyzed. Molecular docking and Western blot experiments were used to study the mechanism of compound 8. The in vivo anti-tumor activity of the compound 8 was evaluated by zebrafish cell derived xenograft (CDX) model. Nineteen known 2-(2-phenylethyl)chromones were isolated from the ethyl acetate extract of agarwood. On A549 (KRAS G12S) cells, compounds 8, 10, and 19 showed good inhibitory activity, on H23 (KRAS G12C) cells, compounds 7, 8, and 19 showed good inhibitory activity, and on H358 (KRAS G12C) cells, compounds 8, 10, and 16 showed good inhibitory activity. Compound 8 had the best inhibitory activity in all three cell lines. It effectively inhibited cell proliferation, clone formation, adhesion ability, and arrested the H23 cell cycle at G2/M phase. Compound 8 could also inhibit the expression of c-Met and its downstream signaling pathways, effectively inhibiting tumor growth in zebrafish CDX model. In conclusion, among the nineteen known 2-(2-phenylethyl)chromones, compound 8 had the best activity and significantly inhibited the proliferation of KRAS-mutant NSCLC cells by arresting the cells in the G2/M phase.

AIM To study the chemical constituents from salt-processed Citri Reticulatae Semen and their antioxidant activities.METHODS The 85% ethanol extract from salt-processed Citri Reticulatae Semen was isolated and purified by silica gel,D101 macroporous resins,MCI,ODS,Sephadex LH-20 and semi-prepative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their antioxidant activities in vitro of the ethanol extract of Citri Reticulatae Semen,salt-processed Citri Reticulatae Semen and all the obtained compounds were evaluated by DPPH and ABTS+assay.RESULTS Sixteen compounds were isolated and identified as limonin(1),obacunone(2),nomilin(3),deacetyl nomilin(4),kaempferol(5),nobiletin(6),diosmetin(7),isosakuranetin(8),hesperetin(9),epicatechin(10),trans-p-menthane-1α,2β,8-triol(11),byakangelicin(12),vanillin(13),p-coumaric acid(14),4-[(1-ethoxy-2-hydroxy)ethyl]phenol(15),catechol(16).Compound 10 showed strong DPPH free radical scavenging activity,with an IC50 value of(0.015±0.001)μmol/mL,and strong ABTS+radical scavenging activity,with an IC50 value of(0.010±0.005)μmol/mL.CONCLUSION Compounds 8,11,15-16 are isolated from genus Citrus for the first time,5,12,14 are obtained from Citri Reticulatae Semen for the first time.Compound 10 shows obvious antioxidant activities.After salt roasting,the antioxidant activity of the ethanol extract of Citri Reticulatae Semen is enhanced.

AIM To study the chemical constituents from the leaves of Citrus reticulata Blanco and their anti-inflammatory activities.METHODS The 85%ethanol extract from the leaves of C.reticulata was isolated and purified by silica gel,D101 macroporous resin,MCI,ODS and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The Griess method was used to determine their inhibitory activities on lipopolysaccharide-induced NO production in macrophages RAW 264.7 cells.The mice foot swelling inflammation model induced by carrageenan was established,and the levels of IL-1β,TNF-α were detected.RESULTS Twelve compounds were isolated and identified as nobiletin(1),tangeretin(2),5-demethylinoblitin(3),5,4'-dihydroxy-6,7,8,3'-tetramethoxy flavone(4),5-hydroxy-7,8,3',4'-trimethoxyflavanone(5),3,5,6,7,8,3',4'-heptamethoxyflavanone(6),hesperetin(7),5-hydroxy-6,7,3',4'-tetramethoxyphenone(8),β-balsam alcohol(9),stigmaster-5-en-3β-alcohol(10),p-hydroxybenzaldehyde(11),vanillin(12).Compounds 1,4,6,7,10 and 12 had strong inhibitory activites on NO release in LPS-induced RAW 264.7 cells,and the IC50 values were(25.21±2.10),(37.77±0.50),(38.19±1.58),(21.89±1.73),(43.81±1.18),(47.98±2.55),(41.23±1.11),(43.80±1.43)μmol/mL,respectively.Compounds 2-3 reduced IL-1β and TNF-α levels(P＜0.05,P＜0.01).CONCLUSION Compounds 6-7,9 are isolated from this plant for the first time.Compounds 1-4,8 exhibit strong in vitro anti-inflammatory activities,and compounds 2-3 exhibit significant in vivo anti-inflammatory activities.

Objective: To investigate the quality of life and associated factors in patients with coronary heart disease (CHD) in China. Methods: A cross-sectional study of 25 provinces and cities in China was performed from June to September 2020. A questionnaire was used to collect the socio-demographic and clinical information of patients with CHD, while the European Five-dimensional Quality of Life Scale (EQ-5D) was used to assess the quality of life. Multiple linear regression model was performed to analyze the associated factors. Results: The median age of the 1 075 responders was 60 (52, 67) years, and 797 (74.1%) were men. The EQ-5D and EQ-VAS indices were 0.7 (0.5, 0.8) and 60.0 (40.0, 80.0). Among the five dimensions in the quality of life scale, the frequency of anxiety/depression was the highest (59.8%), while problems in self-care was the lowest (35.8%). In the multiple linear regression model, female, increasing age, obesity, comorbidity(ies), anxiety/depression, social media channels, and receiving the CABG therapy were associated with the lower EQ-5D index (all P<0.05). In addition, increasing age, obesity, comorbidity (ies), depression, anxiety and depression, social media channels, and receiving the CABG therapy were associated with lower EQ-VAS index (all P<0.05). Conclusion: Over half of the patients with CHD in China have a low quality of life, which is related to gender, age, obesity, treatment pathway, the presence or absence of comorbidity (ies), and psychological state. In addition to managing the adverse effects of traditional socio-demographic factors on the quality of life, clinical practices should pay attention to the psychological state of patients. Moreover, establishing a WeChat group for doctor-patient communication could improve the quality of life of CHD patients.
Male ; Humans ; Female ; Quality of Life/psychology* ; Self Report ; Cross-Sectional Studies ; Coronary Disease ; Surveys and Questionnaires ; Obesity

Objective: To explore the feasibility and safety of the gasless transoral vestibular robotic thyroidectomy using skin suspension. Methods: The clinical data of 20 patients underwent gasless transoral vestibular robotic thyroidectomy in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from February 2022 to May 2022 were retrospectively analyzed. Among them, 18 were females and 2 were males, aged (38.7±8.0) years old. The intraoperative blood loss, operation time, postoperative hospital stay, postoperative drainage volume, postoperative pain visual analogue scale (VAS) score, postoperative swallowing function swallowing impairment score-6 (SIS-6), postoperative aesthetic VAS score, postoperative voice handicap index-10 (VHI-10) voice quality, postoperative pathology and complications were recorded. SPSS 25.0 was used for statistical analysis of the data. Results: The operations were successfully completed without conversion to open surgery in all patients. Pathological examination showed papillary thyroid carcinoma in 18 cases, retrosternal nodular goiter in 1 case, and cystic change in goiter in 1 case. The operative time for thyroid cancer was 161.50 (152.75, 182.50) min [M (P₂₅, P₇₅), the same below] and the average operative time for benign thyroid diseases was 166.50 minutes. The intraoperative blood loss 25.00 (21.25, 30.00) ml. In 18 cases of thyroid cancer, the mean diameter of the tumors was (7.22±2.02) mm, and lymph nodes (6.56±2.14) were dissected in the central region, with a lymph node metastasis rate of 61.11%. The postoperative pain VAS score was 3.00 (2.25, 4.00) points at 24 hours, the mean postoperative drainage volume was (118.35±24.32) ml, the postoperative hospital stay was 3.00 (3.00, 3.75) days, the postoperative SIS-6 score was (4.90±1.58) points at 3 months, and the postoperative VHI-10 score was 7.50 (2.00, 11.00) points at 3 months. Seven patients had mild mandibular numbness, 10 patients had mild cervical numbness, and 3 patients had temporary hypothyroidism three months after surgery and 1 patient had skin flap burn, but recovered one month after surgery. All patients were satisfied with the postoperative aesthetic effects, and the postoperative aesthetic VAS score was 10.00 (10.00, 10.00). Conclusion: Gasless transoral vestibular robotic thyroidectomy using skin suspension is a safe and feasible option with good postoperative aesthetic effect, which can provide a new treatment option for some selected patients with thyroid tumors.
Male ; Female ; Humans ; Adult ; Middle Aged ; Thyroidectomy/adverse effects* ; Robotic Surgical Procedures/adverse effects* ; Retrospective Studies ; Blood Loss, Surgical ; Hypesthesia/surgery* ; Neck Dissection/adverse effects* ; Thyroid Neoplasms/surgery* ; Pain, Postoperative/surgery* ; Postoperative Complications/etiology*

This study was designed to investigate the role of activation of the ferroptosis pathway in the inhibition of esophageal cancer proliferation and metastasis by realgar, using esophageal cancer Eca109 and KYSE150 cells as the target cells. The rate of inhibition and half-inhibitory concentration (IC₅₀) were measured by the CCK-8 method; clone formation ability was measured by clone formation assay; the changes in reactive oxygen species (ROS) were detected by flow cytometry; the ultrastructure of the cells was observed by transmission electron microscopy; the distribution of intracellular iron particles was observed by Prussian blue staining; the expression of glutathione peroxidase 4 (GPX4) was detected by immunofluorescence staining; the scratch assay was used to detect the cell migration ability; the Transwell assay was used to detect the cell invasion ability; and western blotting was used to detect E-cadherin, Slug and N-cadherin protein expression in the cells. The results show that realgar inhibited the proliferation of Eca109 and KYSE150 cells in a time- and concentration-dependent manner, and the IC₅₀ of Eca109 and KYSE150 cells was 64.297 and 51.337 μmol‧L^-1, respectively. Compared with the control group, many mitochondria in the cytoplasm of Eca109 and KYSE150 cells in the realgar 2IC₅₀ group were swollen and blue-stained particles of different sizes and amounts were found, and ROS fluorescence intensity was significantly increased while GPX4 protein expression was significantly reduced (P < 0.01). Compared with the realgar group, the proliferation, migration, membrane penetration and Slug and N-cadherin protein expression were significantly increased, and the cell inhibition rate and E-cadherin protein expression were significantly decreased in Eca109 and KYSE150 cells in the realgar+ZVAD-FMK group (P < 0.05). The proliferation, migration, membrane penetration and Slug and N-cadherin protein expression were significantly decreased, and the cell inhibition rate and E-cadherin protein expression were significantly increased of Eca109 and KYSE150 cells in the realgar +erastin group (P < 0.05). The above results show that realgar inhibited the proliferation of Eca109 and KYSE150 cells and induced partial ferroptosis in the cells, and the proliferation and metastasis effects of realgar on esophageal cancer cells may work through partial ferroptosis pathway activation.

Objective: To evaluate the feasibility, safety, and short-term efficacy of robotic lateral neck dissection via combined axillary-retroauricular approach for N1b papillary thyroid carcinoma (PTC). Methods: Thirty patients with cT1-2N1bM0 PTC who received robotic lateral neck dissection via combined axillary-retroauricular approach were included in the Department of Otorhinolaryngology of Sun Yat-sen Memorial Hospital from December 2016 to December 2020. There were 10 males and 20 females, with a median age of 34.5 years and a median body mass index of 25.55 kg/m². The clinical, surgical, complications, pathology and follow-up data were analysed with SPSS 25.0 software package. Results: The median operative time of 30 patients was 255.50 min, the median operative blood loss was 69.00 ml, and the median postoperative hospital stay was 6.00 days. The incidence of postoperative temporary recurrent laryngeal nerve paralysis was 3.33% (1/30), temporary hypoparathyroidism was 16.67%(5/30), temporary accessory nerve injury was 3.33% (1/30), hematoma was 3.33% (1/30) and chylous leakage was 3.33% (1/30). The median visual analogue scale (VAS) score was 8.00, and the follow-up time was 13-38 months, with a median of 25.5 months. One case showed cervical lymph node recurrence 14 months after surgery. The most recent dynamic recurrence risk stratification showed 21 patients (70.00%) had excellent responses. Conclusions: Robotic lateral neck dissection via combined axillary-retroauricular approach for unilateral cN1b PTC is safe, feasible and aesthetic. The short-term efficacy and dynamic recurrence risk stratification results of short-term follow-up are satisfactory. It can provide a surgical option for cN1b PTC patients.
Adult ; Carcinoma, Papillary/surgery* ; Female ; Humans ; Male ; Neck Dissection/methods* ; Retrospective Studies ; Robotic Surgical Procedures ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/surgery* ; Thyroidectomy/methods*

Objective: To investigate the safety, efficacy, locally control and survival results of transoral Da Vinci robotic surgery for salvage treatment of locally recurrent nasopharyngeal carcinoma. Methods: This retrospective study included 33 patients with locally recurrent nasopharyngeal carcinoma (stage rT1-2, partial rT3) underwent transoral Da Vinci robotic surgery between October 2017 and January 2020. There were 20 males and 11 females, with an average age of (47.9±10.5) years. The lesions were localized in nasopharyngeal cavity in 14 cases, with extending to parapharyngeal space in 6 cases and the floor of sphenoid sinus in 13 cases. Transnasal endoscopy was used to assist surgery if necessary. SPSS 25.0 statistical software was used for statistical analysis. Results: Transoral robotic nasopharyngectomy was successfully performed in all cases without conversion to open surgery, of which 13 cases were combined with transnasal endoscopic surgery. The average operation time was (126.2±30.0) min, ranging from 90 to 180 min. The postoperative pathological margin was R0 (31 cases) and R1 (2 cases), with no tumor residue. Complications of surgery mainly included symptoms of headache, nasal dryness and velopharyngeal insufficiency without nasopharyngeal hemorrhage. Follow-up time was from 3 to 54 months. One case had tumor recurrence 11 months after operation, 1 case had ipsilateral cervical lymph node metastasis 27 months after operation, 2 cases had distant metastasis and 1 case died of nasopharyngeal hemorrhage 3 months after operation. The 1-year, 2-year and 3-year overall survival rates were 97.0%, 96.0% and 92.9%, respectively and the local recurrence free rates were 97.0%, 95.7% and 91.7%, respectively. Conclusion: Transoral robotic nasopharyngectomy is safe and feasible for local recurrent nasopharyngeal carcinoma in selected patients, with higher local control rate and quality of life.
Adult ; Female ; Humans ; Male ; Middle Aged ; Nasopharyngeal Carcinoma/surgery* ; Nasopharyngeal Neoplasms/pathology* ; Neoplasm Recurrence, Local/surgery* ; Quality of Life ; Retrospective Studies ; Robotic Surgical Procedures

Objective: To evaluate multidrug resistant loop-mediated isothermal amplification (MDR-LAMP) assay for the early diagnosis of multidrug-resistant tuberculosis and to compare the mutation patterns associated with the Methods: MDR-LAMP assay was evaluated using 100 Results: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDR-LAMP were 85.5%, 93.6%, 96.7%, and 74.4% for the detection of resistance to isoniazid and rifampicin, respectively, and 80.5%, 92.3%, 98.6%, and 41.4% for the detection of Conclusion MDR-LAMP is a rapid and accessible assay for the laboratory identification of rifampicin and isoniazid resistance of
Antitubercular Agents ; Bacterial Proteins/genetics* ; Catalase/genetics* ; DNA, Bacterial/analysis* ; DNA-Directed RNA Polymerases/genetics* ; Drug Resistance, Multiple, Bacterial/genetics* ; Isoniazid ; Molecular Diagnostic Techniques/methods* ; Mutation ; Mycobacterium tuberculosis/isolation & purification* ; Nucleic Acid Amplification Techniques/methods* ; Oxidoreductases/genetics* ; Phenotype ; Rifampin ; Whole Genome Sequencing

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*