OBJECTIVE To elucidate the mechanisms responsible for the inhibitory effects of limonene on the proliferation of non-small cell lung cancer(NSCLC) by non-targeted metabolomics and additional approaches. METHODS The CCK-8 assay was utilized to evaluate the inhibitory effects of limonene on NSCLC A549 cell viability and to ascertain the IC50. In vitro experiments, encompassing colony formation, flow cytometry, iron content assessment, and mitochondrial staining, were conducted to assess the anti-lung cancer and iron-induced cell death effects of limonene. Metabolomic analysis was employed to identify potential pathways influenced by limonene, and Western blotting was carried out to validate pivotal proteins within these pathways. RESULTS In comparison to the control group, the limonene-treated group demonstrated a significant, dose-dependent reduction in A549 cell proliferation and colony formation. Optical microscopy revealed cellular detachment and pronounced changes in cellular morphology following exposure to limonene. Limonene induced apoptosis in A549 cells and arrested them in the G0-G1 phase of the cell cycle. Confocal microscopy unveiled diminished mitochondrial fluorescence and an augmented intracellular iron content, indicative of the classical phenomenon of ferroptosis. Metabolomic investigations unveiled divergent metabolic pathways, including glutathione(GSH) metabolism, arginine biosynthesis, D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism, with many of them intricately linked to intracellular GSH synthesis. Western blotting experiments underscored a marked reduction in the levels of SLC40A1, SLC7A11(xCT), and GPX4 proteins within the cells post-limonene treatment. CONCLUSION Limonene may induce ferroptosis in lung cancer cells by reducing GSH synthesis and increasing Fe2+ levels.

Objective:To evaluate the efficacy and safety of pembrolizumab plus nab-paclitaxel and platinum as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (R/M HNSCC).Methods:This was a prospective, single-arm, open label, phase 2 clinical study enrolling patients at the Cancer Hospital of the Chinese Academy of Medical Sciences with R/M HNSCC treated with pembrolizumab plus nab-paclitaxel and cisplatin or carboplatin. After six cycles of treatment, patients received pembrolizumab as maintenance therapy until disease progression or intolerable toxicity or completion of 35 cycles of treatment. The primary endpoint was objective response rate, and secondary endpoints included overall survival, progression-free survival, and safety profile. Efficacy was evaluated according to the response evaluation criteria in solid tumors 1.1, survival analysis was performed using the Kaplan-Meier method, and adverse events were assessed using the America National Cancer Institute Common Terminology Criteria for Adverse Events 5.0.Results:A total of 30 patients with R/M HNSCC were enrolled from 23 April 2021 to 22 March 2023, including 28 males and 2 females, with a median age of 67 years. The median follow-up time was 14.5 months, the objective response rate was 70.0%, the disease control rate was 96.7%, and the median progression-free survival and overall survival of all patients were 11.6 months and 18.8 months, respectively. Median duration of response was up to 17.3 months. Grade≥3 treatment-related adverse events were leukopenia (26.7%), neutropenia (26.7%), peripheral neurotoxicity (3.3%), rash (3.3%), hyperalgesia (3.3%), and immune-related pneumonitis (3.3%). The most common immune-related adverse event was hypothyroidism (40.0%).Conclusion:Pembrolizumab combined with nab-paclitaxel and platinum shows encouraging antitumor activity accompanied with a manageable safety profile in untreated R/M HNSCC patients in China.

Objective:To observe the effect of well-designed board sanding training on the upper extremity motor functioning of hemiplegic stroke survivors.Methods:Sixty stroke survivors with hemiplegia were randomly divided into an observation group (30 cases) and a control group (30 cases). All received conventional rehabilitation. The observation group′s training involved intelligent board sanding, while the control group′s training involved traditional sanding.Results:After the treatment, significant improvement was observed in the Fugl-Meyer upper extremity scores, modified Barthel index scores and reported shoulder pain in both groups, with the observation group′s averages significantly better than those of the control group. After the intervention, the average scores of both groups on the modified Ashforth scale had also improved significantly.Conclusions:Supplementing conventional rehabilitation treatment with intelligent board sanding can significantly improve upper extremity motor function and ability in the activities of daily living of stroke survivors with hemiplegia while somewhat relieving shoulder pain. The effect is better than with traditional board sanding.

Objective To study the clinical use of microwave scalpel in hepatectomy for hepatocellular carcinoma without hepatic vascular inflow occlusion.Methods A retrospective study was conducted on the clinical data of 126 consecutive patients with hepatocellular carcinoma who were treated at the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Sun Yat-sen University from December 2015 to August 2018.The patients included 111 males and 15 females,with ages which ranged from 25 to 75 years.These patients were divided into two groups by the different surgical resection methods:the microwave scalpel hepatectomy (MSH) group which employed microwave scalpels to perform hepatectomy (n =42),and the ultrasound scalpel hepatectomy (USH) group which employed ultrasound scalpels (n =84).The perioperative conditions which included baseline data,amount of intraoperative bleeding,liver function after operation,and morbidity of postoperative complications were compared.Results There were no significant differences in the preoperative indexes which included tumor diameter,number of tumors,levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) between the 2 groups (all P ＞ 0.05).In the MSH group,the amount of intraoperative bleeding was 100.0 (100.0,200.0) ml,which was significantly lower than the 300.0 (100.0,400.0) ml in the USH group (P ＜ 0.05).Compared with the USH group,the levels of AST and ALT on postoperative day 1,3,7 after operation in the MSH group were significantly lower (all P ＜ 0.05),and the corresponding albumin levels were significantly higher than the USH group (P ＜0.05).The incidence of complications was 4.8％ (2/42) in the MSH group which was significantly lower than that of 20.2％ (17/84) in the USH group (P ＜ 0.05).Conclusion Microwave scalpel significantly reduced intraoperative bleeding and postoperative complications,and led to less liver functional injury.

Objective To analyze the clinical features of patients with coronavirus disease 2019 (COVID-19) in Shanghai and to investigate the risk factors for disease progression to severe cases. Methods The clinical data of 292 adult patients with COVID-19 hospitalized in Shanghai Public Health Clinical Center from January 20, 2020 to February 10, 2020 were retrospectively analyzed, including 21 severe patients and 271 mild patients. The demographic characteristics, epidemiological history, history of underlying diseases and laboratory examinations were compared between the two groups. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using hi-square test. The binary logistic regression equation was used to analyze the risk factors for the progression of patients to severe cases. Results Among the 292 patients, 21 were severe cases with the rate of 7.2% (21/292). One patient died, and the mortality rate was 4.8% in severe patients. The severe patients aged (65.0±15.7) years old, 19 (90.5%) were male, 11 (52.4%) had underlying diseases, 7 (33.3%) had close relatives diagnosed with COVID-19. The mild patients aged (48.7±15.7) years old, 135 (49.8%) were male, 74 (27.3%) had underlying diseases, 36 (13.3%) had close relatives diagnosed with COVID-19. The differences between two groups were all significant statistically ( t =-4.730, χ 2 =12.930, 5.938 and 4.744, respectively, all P <0.05). Compared with the mild patients, the levels of absolute numbers of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine, serum cystatin C, C reactive protein (CRP), procalcitonin , D -dimer, pro-B-type natriuretic peptide (proBNP), serum myoglobin, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum troponin I (cTnI) in severe patients were all significantly higher ( U =2 091.5, 1 928.0, 1 215.5, 729.0, 1 580.5, 1 375.5, 917.5, 789.5, 1 209.0, 1 434.0, 638.0, 964.5, 1 258.0 and 1 747.5, respectively, all P <0.05), while the levels of lymphocyte count, albumin, transferrin, CD3 + T lymphocyte count, CD8 + T lymphocyte count and CD4 + T lymphocyte count in severe patients were all significantly lower ( U =1 263.5, t =4.716, U =1 214.0, 962.0, 1 167.5 and 988.0, respectively, all P <0.05). Further logistic regression analysis showed that the albumin (odds ratio ( OR )=0.806, 95% CI 0.675-0.961), CRP ( OR =1.016, 95% CI 1.000-1.032), serum myoglobin ( OR =1.010, 95% CI 1.004-1.016), CD3 + T lymphocyte count ( OR =0.996, 95% CI 0.991-1.000) and CD8 + T lymphocyte count ( OR =1.006, 95% CI 1.001-1.010) at admission were independent risk factors for the progression of COVID-19 patients to severe illness (all P <0.05). Conclusions Severe cases of patients with COVID-19 in Shanghai are predominantly elderly men with underlying diseases. Albumin, CRP, serum myoglobin, CD3 + T lymphocyte count and CD8 + T lymphocyte count could be used as early warning indicators for severe cases, which deserve more clinical attention.

Parenteral nutrition-associated liver disease (PNALD) is a liver dysfunction caused by various risk factors presented in patients receiving total parenteral nutrition (TPN). Omega-6 rich Intralipid® and omega-3 rich Omegaven® are two intravenous lipid emulsions used in TPN. TPN could affect the hepatic expression of genes in anti-oxidative stress, but it's unknown whether TPN affects genes in drug metabolism. In this study, either Intralipid®- or Omegaven®-based TPN was administered to mice and the expression of a cohort of genes involved in anti-oxidative stress or drug metabolism was analyzed, glutathione (GSH) levels were measured, and protein levels for two key drug metabolism genes were determined. Overall, the expression of most genes was downregulated by Intralipid®-based TPN ( and ). Omegaven® showed similar results as Intralipid® except for preserving the expression of and and increasing . Total GSH levels were decreased by Intralipid®, but increased by Omegaven®. CYP3A11 protein levels were increased by Omegaven®. In conclusion, TPN reduced the expression of many genes involved in anti-oxidative stress and drug metabolism in mice. However, Omegaven® preserved expression of , suggesting another beneficial effect of Omegaven® in protecting liver functions.

Objective To investigate the roles of cerebral metabolic rate for oxygen (CMRO2) monitoring in the evaluation of cerebral function after cardiopulmonary resuscitation (CPR) through transcranial doppler (TCD) and SjvO2. Methods In this prospective/retrospective analysis, we included 46 cases admitted to the general intensive care unit (GICU) of the Second Affiliated Hospital of Soochow University from January 2012 to December 2014. Upon admission, TCD and SjvO2 were performed,and the patients' characteristics were recorded. Based on the CPC score upon GICU discharge, the patients were divided into two groups with satisfactory cerebral function and poor cerebral function, respectively. Then the clinical symptoms, cerebral blood flow (CBF), a-vDO2, SjvO2 and CMRO2 were analyzed, followed by investigating their correlation with the prognosis of cerebral function. The measurement data that were normally distributed were presented by mean ± standard deviation. Student's t test was utilized for the inter-group comparison. Correlation analysis was performed. ROC was plotted, followed by evaluating roles of each index in the specificity and sensitivity of nervous prognosis. Results No statistical differences were noted in the gender, age, initial monitoring indicators, ICU duration and initial GCS between the two groups (P>0.05). The CA-ROSC time and APACHE II score in the satisfactory cerebral function group were significantly shorter than those of the poor cerebral function group (P<0.05). The SjvO2 in the satisfactory cerebral function group was significantly lower than that of the poor function group (67.33±10.30 vs. 76.89±13.08, t=-3.579, P<0.05). The Vs and Vd as revealed by TCD in the satisfactory function group were higher than those of the poor function group, together with the CBF. Significant decrease was noted in the PI and RI in the satisfactory function group compared with that of the poor function group (P<0.05). Besides, the CMRO2 and a-vDO2 in the satisfactory function group showed significant increase compared with those of the poor function group (P<0.05). ROC indicated that CMRO2, CBF, a-vDO2 and SjvO2 could be utilized for the evaluation of cerebral function, among which CMRO2 showed the highest accuracy for the cerebral function prognosis. Conclusions CMRO2, CBF, a-vDO2 and SjvO2 were associated with cerebral function prognosis. CMRO2 was the most appropriate parameter to evaluate the oxygen metabolism in brain tissues, which could evaluate the prognosis of cerebral function.

BACKGROUND AND OBJECTIVES: For the present study, we investigated the factors that influence the quality of standardized treatment for patients with post-cardiac arrest syndrome (PCAS) to improve the quality of PCAS treatment. SUBJECTS AND METHODS: We collected data on patients with cardiac arrest (CA) who were admitted to the intensive care units (ICUs) of 11 hospitals-Class II Grade A or above-in Suzhou from January to October 2013. Indexes of standardized treatment were observed within 72 hrs of CA. We analyzed monitoring techniques, monitoring frequency, ICU human and material resources, and intensivists' knowledge of PCAS treatment to explore how those factors affected the management of patients with PCAS. RESULTS: The bed/nurse ratio and the frequency with which core temperature was recorded correlated closely with the implementation of therapeutic hypothermia (TH) within 6 hrs of CA. The bed/doctor ratio and intensivists' knowledge about PCAS correlated closely with high-quality blood glucose control within 6 hrs of CA. Furthermore, the frequency with which core temperature was recorded was an independent factor influencing the quality of TH implementation, and the number times blood gas was analyzed was an independent factor influencing how well partial pressure of carbon dioxide was kept within the normal range in the 6 hrs after CA. CONCLUSION: The frequency of core temperature measurements and the number of times blood gas is analyzed are the most important factors influencing the quality of standardized treatment for patients with PCAS.
Blood Glucose ; Carbon Dioxide ; Heart Arrest ; Humans ; Hypothermia, Induced ; Intensive Care Units ; Partial Pressure ; Passive Cutaneous Anaphylaxis ; Reference Values

Objective:To elucidate the factors influencing the differences in the survival rates of esophageal squamous cell carcinoma (ESCC) patients between the rural and urban regions in China. Methods:A total of 36,723 ESCC patients derived from the clinical data-bases containing 500,000 esophageal and gastric cardia carcinoma cases (1973-2015) of the Henan Key Laboratory for Esophageal Can-cer Research of the First Affiliated Hospital, Zhengzhou University, were analyzed. Of these patients, 33,625 were from the rural re-gions (91.6%), comprising 20,906 male patients with an average age of 58.98 ± 8.71 years and 12,719 females with an average age of 59.59 ± 8.53 years. The remaining 3,098 were from the urban regions and composed of 2,089 male patients with an average age of 60.84±9.10 years and 1,009 females with an average age of 62.46 ± 9.14 years. All the patients underwent radical esophagectomy, de-tailed histopathological diagnosis, and TNM staging. Chi square test, Kaplan-Meier, Log-rank, and Cox proportional hazards regression model were used to analyze the differences between ESCC patients from rural regions and those from urban regions and among the risk factors in prognosis. Results:Kaplan-Meier and Log-rank analysis results showed that the ESCC patients from the rural regions had significantly higher overall survival than the urban patients (χ2=12.971, P=0.000). Further analysis showed that rural patients≥50 years old and diagnosed with stage IIa and IIb (middle stage) ESCC had higher survival rates than urban patients in males and females (male:χ2=16.188, P<0.001;female:χ2=5.019, P=0.025). However, the survival rates of rural and urban patients with stage 0,Ⅰa,Ⅰb (early stage) and Ⅲa, Ⅲc, and Ⅳ (late stage) were similar (P>0.05). The results of Cox proportional hazards regression model analysis showed that age, gender, and TNM stages were independent risk factors for rural and urban ESCC patients. When the rural and urban ESCC patients were both considered, the Cox proportional hazards regression model analysis results showed that male ESCC patients≥50 years old, urban residence, and TNM stages were independent risk factors. Conclusion:Rural ESCC patients have significantly high-er overall survival than urban patients. Male, age of≥50 years old, urban residence, and TNM stages were independent risk factors for ESCC patient survival.

Objective:To characterize the clinical and epidemiological changes, treatments, and prognoses of primary esophageal small cell carcinoma (PESC). Methods:A retrospective analysis was conducted using the clinical epidemiology data of 529 PESC patients se-lected from the clinical databases of 500,000 esophageal and gastric cardiac carcinomas of the Henan Key Laboratory for Esophageal Cancer Research (1992-2015). Among these patients, 241 cases were included in the survival analysis. The five-year survival rate was calculated using Kaplan-Meier analysis, and the differences in survival rates were compared using the Log-rank analysis model. Re-sults:All 529 PESC cases were analyzed, which accounted for 0.2%of esophageal cancers diagnosed in the same period. The incidence of PESC increased annually (R2=0.574). The survival rates for 1-, 2-, 3-, and 5-year of 241 PESC patients were 55%, 40%, 29%, and 9%, respectively, and the median survival time was 21.9 months. On the basis of the VALSG criteria of lung small cell carcinoma, a statisti-cal difference was observed in the overall survival rates for limited and extensive diseases (P=0.003), with the median survival time of 24.3 and 17.5 months, respectively. Furthermore, significant differences were observed on survival with various treatment modalities (P=0.004). The median survival time of PESC patients treated with combined surgery and radiochemotherapies (28.8 months) was lon-ger than those with either chemotherapy (17.8 months, P=0.015) or chemoradiotherapy (14.5 months, P=0.004). In limited disease pa-tients, the median survival time was longer in patients treated with surgery (27.7 months) than in those without surgery (16.2 months, P=0.007). Notably, the biopsy diagnosis before surgery for PESC was only 40.8%. Conclusion:PESC is a rare malignant carcinoma with increasing incidence. PESC presents poor prognosis, and the survival rate can be improved through combined therapies based on sur-gery. A high misdiagnosis rate for PESC is observed before surgery with biopsy.