BACKGROUND: Immune checkpoint inhibitors (ICIs) have been included in various neoadjuvant therapy (NAT) regimens for non-small cell lung cancer (NSCLC). However, due to the relatively short period for the use of ICIs in NAT, patients' clinical outcomes with different regimens are uncertain. Our study aims to examine the efficacy of neoadjuvant immunotherapy (NAIT) for NSCLC patients and compare the overall survival (OS) and event-free survival (EFS) of patients receiving different NAT regimens. METHODS: This study retrospectively included 308 NSCLC patients treated with different NAT regimens and subsequent surgery in National Cancer Center between August 1, 2016 and July 31, 2022. Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the prognosis of patients. RESULTS: With a median follow-up of 27.5 months, the 1-year OS rates were 98.8% and 96.2%, and the 2-year OS rates were 96.6% and 85.8% in patients of the NAIT and neoadjuvant chemotherapy (NACT) group, respectively (hazard ratio [HR], 0.339; 95% confidence interval [CI], 0.160-0.720; P = 0.003). The 1-year EFS rates were 96.0% and 88.0%, and the 2-year EFS rates were 92.0% and 77.7% for patients in the NAIT and NACT groups, respectively (HR, 0.438; 95% CI, 0.276-0.846; P = 0.010). For patients who did not achieve pathological complete response (pCR), significantly longer OS ( P = 0.012) and EFS ( P = 0.019) were observed in patients receiving NAIT than those receiving NACT. Different NAT regimens had little effect on surgery and the postoperative length of stay (6 [4, 7] days vs . 6 [4, 7] days, Z = -0.227, P = 0.820). CONCLUSIONS NAIT exhibited superior efficacy to NACT for NSCLC, resulting in longer OS and EFS. The OS and EFS benefits were also observed among patients in the NAIT group who did not achieve pCR.
Humans ; Carcinoma, Non-Small-Cell Lung/mortality* ; Male ; Female ; Lung Neoplasms/mortality* ; Middle Aged ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy/methods* ; Retrospective Studies ; Aged ; Adult ; Kaplan-Meier Estimate ; Treatment Outcome ; Immunotherapy/methods*

Objective To observe the levels of serum thymidine kinase 1(TK1)and secreted protein Dikkopf-1(DKK1)in patients with advanced non-small cell lung cancer(NSCLC),and analyze the relation-ship between serum TK1,DKK1 and the prognosis of NSCLC.Methods This study adopted a prospective co-hort study method,a total of 91 chemotherapy patients with advanced NSCLC admitted in Jinshan Branch of Shanghai Sixth People's Hospital from January 2020 to June 2021 were enrolled as the research objects.All patients received the detection of serum TK1 and DKK1 on admission,completed 4 chemotherapy cycles in Jinshan Branch of Shanghai Sixth People's Hospital and were followed up for 3 months.The disease remission rate was evaluated according to the relevant standards.The patients with complete remission and partial re-mission were included in the good prognosis group,and those with the stable and progressive lesions were in-cluded in the poor prognosis group.The levels of serum TK1 and DKK1 were compared between the two groups.Logistic regression was used to analyze the relationship between the levels of serum TK1 and DKK1 and the prognosis of patients with advanced NSCLC.Results Among 91 patients with advanced NSCLC who received chemotherapy,threre were 58 cases(63.74％)in the good prognosis group,and 33 cases(36.26％)in the poor prognosis group.The levels of serum carcinoembryonic antigen(CEA),TK1 and DKK1 in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).Logistic regression anal-ysis showed that the high levels of serum TK1 and DKK1 were the influencing factors of poor prognosis in pa-tients with advanced NSCLC(OR＞1,P＜0.05).The receiver operating characteristic curve was drawn,and the results showed that the area under the curve of serum TK1,DKK1 alone and combined for predicting the poor prognosis in patients with advanced NSCLC was＞0.700,all of which had certain predictive value,and the predictive value of the combined detection was the highest.Conclusion The abnormal increase of serum TK1 and DKK1 levels may indicate a high risk of poor prognosis in patients with advanced NSCLC.Early monito-ring of serum TK1 and DKK1 levels in patients has certain positive significance for predicting and evaluating the prognosis of patients.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67％,8.83％,16.16％,22.16％and 30.83％,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.
Humans ; Mice ; Animals ; Depression/drug therapy* ; Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba

Objective:To retrieve, evaluate and integrate the best evidence of home exercise rehabilitation for peritoneal dialysis patients, so as to provide basis for formulating home exercise rehabilitation plan for peritoneal dialysis patients.Methods:Evidence-based problems were constructed according to the PICO (population, intervention, control and outcome) principle. The home exercise rehabilitation guideline, expert consensus, evidence summary, systematic review, and randomized controlled trial of peritoneal dialysis patients were systematically searched in the evidence-based resource databases such as UpToDate, British Medical Journal (BMJ) Best Practice, Guidelines International Network, and in the comprehensive databases such as PubMed, Embase, and Web of Science. The retrieval time limit was from the establishment of the database to November 20, 2021. Two researchers with evidence-based knowledge independently evaluated the quality of the article and the level of evidence.Results:A total of 10 articles were included, including one evidence summary, one practical suggestion, one expert consensus, two systematic reviews, and five randomized controlled trials. A total of 24 best evidences were summarized from 8 aspects, including applicable population, starting time, exercise evaluation, exercise prescription formulation, exercise type, exercise frequency and duration, exercise intensity and exercise precautions.Conclusions:The best evidence of home exercise rehabilitation for peritoneal dialysis patients provides a certain evidence-based basis for the selection of home exercise rehabilitation programs for peritoneal dialysis patients.

Valproic acid is a first-line broad-spectrum antiepileptic drug, however, the pharmacokinetics of valproic acid are affected by many factors, such as heredity, drug combination and so on. So, how to realize the individualized dosing regimen of valproic acid has received much attention. Population pharmacokinetics combines classical pharmacokinetic principles and population statistical models to quantitatively evaluate the influence factor of drug concentration in the patient population. Thus, it can optimize characterization of the differences among individuals. This article reviews the researches about valproic acid in recent years, and summarizes the effect of the factors on the metabolism of valproic acid, such as drug combination and gene polymorphism. Additionally, focus on the latest research progress of individual administration of valproic acid under the guidance of population pharmacokinetics.

Objective To report the experience of the arterial switch operation(ASO) for Taussig-Bing anomaly and late outcomes.Methods From January 2001 to December 2015,57 patients were underwent arterial switch operation for Taussig-Bing anomaly in Fudan university affiliated children's hospital cardiac center,Median age and weight at operation was 63(37.5-88.5)days, 4.1(3.4-5.0)kg, respectively.29 patients with Arch anomalies(50.9%), 23 patients with unusual coronaries(40.3%),according to have arch anomaly or not and surgery time, dividing the patients into two groups, group A(have, n=29)and group B(not have, n=28), earlier experience into group 1(2001-2008, n=27), later experience into group 2(2009-2015, n=30), respectively.Results The Mortality was12.3%, the mortality of group A and group B was 13.8%, 10.7%(P>0.05),group 1 and group 2 was 22.2%, 3.3%(P<0.05) respectively, follow up was complete in 47 patients with a mean follow-up of(6.2±3.5) years , three patients lost, there was no late mortality, the actual survival at 1, 5year was 87%, 87%, respectively.Reintervention was required in 10 patients(21.3%), the aorta-PA valve diameter ratio was a risk factor for reintervention(group A P=0.02, group B P=0.04) ,and 1,2,5year free of reintervention was 95.6%, 86.6%, 77.2%, respectively.Conclusion The ASO approach can be applied to Taussig-Bing anomaly with acceptable mortality , and it is the procedure of choice at our institution.One stage to repair TBA with aortic arch abnormalities did not influence outcomes.The aorta-PA valve diameter ratio<0.5 was a risk factor for reintervention.

Objective: To investigate the clinicopathological features, morphological characteristics, immunophenotypes of littoral cell angioma (LCA) in spleen, and to provide new evidence for making diagnosis and avoiding misdiagnosis.Methods: Clinicopathological data, histological characteristics of 13 cases of LCA were retrospectively studied and immunohistochemical staining was imposed on the paraffi-nembedded specimens, and 5 cases of cavernous hemangioma, 4 cases of normal littoral cells of spleens were used as control groups, simultaneously.Results: All the 13 LCA patients included 7 males and 6 females, aged from 39 to 70 years with an average of 54.2 years and a median age of 55 years.Among these tumor patients, 6 cases were accompanied by malignances, benign tumors or inflammation states at abdominal cavities, and 7 cases were accidentally discovered by physical examinations.Grossly, spleens contained solitary or multiple gray red nodules ,which ranged from 0.5 to 6.2 cm in diameter.Histologically, tumors were composed by anastomosing vascular spaces which were lining by plump, rounded to cuboidal littoral cells that extended into vascular lumens.Usually, papillary frameworks that were covered by these cells were also seen extending into the lumens in some areas.Other types of histiocytoid cells were identified in lumens and the sizes were larger than the littoral cells.Both types of cells absented cytologic atypia.Immunohistochemical study demonstrated that the littoral cells in all cases were positive for vascular endothelial and histiocyte markers, such as CD21, CD31, CD68, polyclone FⅧRAg and ERG, while these cells were negative for CD8, CD34, and WT-1.These findings manifested that immunophenotype of littoral cell in LCA distinctive from that in controls.Conclusion: LCA is a benign lesion, which frequently occurs in the elderly.Its etiology remains confusion, however, immune dysregulation may associate with it because of the concomitance with other tumor or inflammation in some cases.The littoral cells in LCA show a hybrid endothelial-histiocytic phenotype on immunohistochemistry, therefore these cells may have features that intermediate between those of endotheliocytes and histiocytes.Emphasizing the histological findings and immunophenotypes is significant for diagnosis and differential diagnosis.

[ABSTRACT]OBJECTIVETo investigate the effect of accurate airway humidification on hemorrhage, pharyngalgia, mucosal edema and sputum viscosity in patients with low-temperature plasma coblation-assisted tonsillectomy.METHODS58 cases were divided into three groups by using random numbers.In accurate airway humidification group, atomizing inhalation was carried out by AIRVOTM series apparatus; in oxygen atomizing group, budesonide suspension was used; in control group, saline was used. We evaluated the hemorrhage, pharyngalgia, mucosal edema and sputum viscosity in 3 consecutive postoperative days.RESULTSPharyngalgia in accurate airway humidification group and in oxygen atomizing group were both significantly reduced than that of the control group (P<0.001). Besides, in accurate airway humidification group, mucosal edema and sputum viscosity were significantly improved than that of the oxygen atomizing group (P<0.05) and control group (P<0.05).CONCLUSIONAccurate airway humidification could reduce the complications such as pharyngalgia, mucosal edema and purulent sputum after low-temperature plasma coblation-assisted tonsillectomy, and could accelerate recovery from surgery.