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 investigate the improvement mechanism of Huatan tongmai decoction on rats with polycystic ovary syndrome （PCOS） by regulating autophagy through phosphatidylinositol-3-kinase（PI3K）/protein kinase B（AKT）/mammalian target of rapamycin （mTOR） pathway. METHODS A total of 40 rats were randomly divided into blank group （purified water）， model group （purified water）， traditional Chinese medicine group [Huatan tongmai decoction， 24 g/（kg·d）] and chemical drug group [metformin， 0.16 g/（kg·d）]， with 10 rats in each group. Except for blank group， other groups were given a combination of high-fat diet and intragastric administration of 1 mg/kg letrozole suspension to establish PCOS rat model. After modeling， they were given relevant medicine or water intragastrically， once a day， for 42 consecutive days. After the last administration， the pathological and ultrastructural changes of ovarian tissue were observed. The levels of follicle stimulating hormone （FSH）， testosterone （T）， estradiol （E2） ，luteinizing hormone （LH） in serum were detected，and the LH/FSH ratio was calculated. mRNA expressions of Beclin-1， p62 and microtubule-associated protein 1 light chain 3 （LC3） in ovarian tissue were detected. The expressions of related proteins of PI3K/AKT/mTOR pathway and autophagy in rat ovarian tissues were also detected. RESULTS Compared with blank group， the pathological damage and ultrastructural changes of the ovarian tissue in the model group rats were obvious， and a large number of autophagosomes could be seen in cells. The levels of T and LH and the LH/FSH ratio in serum， as well as mRNA and protein expressions of Beclin-1 and LC3， were increased significantly （P＜0.05）， while the levels of E2 and FSH in serum， as well as mRNA and protein expressions of p62 and the phosphorylation levels of PI3K， AKT and mTOR proteins in ovarian tissue， were significantly decreased （P＜0.05）. Compared with model group， the pathological damage of ovarian tissue in the administration groups was significantly reduced， the number of autophagosomes was smaller， and the expression levels of the above indicators were significantly reversed （P＜0.05）. CONCLUSIONS Huatan tongmai decoction can inhibit autophagy in ovarian granular cells by activating the PI3K/AKT/mTOR pathway， regulate the secretion of sex hormones， alleviate pathological damage in ovarian tissues， and promote normal follicular development， thereby exerting an ameliorative effect on PCOS rats.

Traditional Chinese medicine of Polygonum cuspidatum has been utilized in China for thousands of years. Its primary active compound, polydatin, exhibits a variety of pharmacological effects including the regulation of glucose and lipid metabolism, suppression of cough and asthma, as well as antibacterial and anti-inflammatory properties. However, conventional methods for polydatin production are inadequate to satisfy the market demand. This study aims to explore the green and efficient preparation of polydatin. With resveratrol as the substrate, we efficiently synthesized polydatin by using the triple mutant IGW (Y14I/I62G/M315W) of the glycosyltransferase UGT_BS based on a strategy of two-enzyme coupled with one-pot and realized the recycling of uridine diphosphate-glucose (UDPG). The conditions of the two-enzyme reaction were optimized. Under the conditions of 35 ℃, pH 8.0, IGW: AtSuSy1 activity ratio of 3:4, dimethyl sulfoxide (DMSO) volume fraction of 5%, uridine diphosphate (UDP) concentration of 0.10 mmol/L, and sucrose concentration of 0.6 mol/L, the conversion of 2 mmol/L resveratrol reached 80.6% within 1 h, and the proportion of polydatin was over 90%. This study achieved the recycling of UDPG via a two-enzyme coupling system and shortened the reaction time. At the same time, the fed-batch strategy was adopted, and the yield of polydatin reached 6.28 g/L after 24 h in the one-pot coupling reaction, which provided a new strategy for green and efficient preparation of polydatin.
Stilbenes/chemistry* ; Glucosides/biosynthesis* ; Resveratrol ; Fallopia japonica/chemistry* ; Glycosyltransferases/genetics*

Objective:To investigate the mechanism of proanthocyanidin (PA) in regulating the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs), and to explore the effects of PA on the expression and nuclear translocation of transcription factor EB (TFEB) and on the autophagy-lysosome pathway.Methods:PDLSCs were divided into control group and PA group, which were subjected to RNA sequencing analysis (RNA Seq) to detect differentially expressed genes. The osteogenic differentiation ability and autophagy level were observed by real-time fluorescence quantitative PCR (RT-qPCR) analysis, alkaline phosphatase (ALP) staining and transmission electron microscope (TEM), respectively. Scratch assay and Transwell assay were used to detect the migration ability of PDLSCs. Lysotracker and immunofluorescence staining were used to detect the biogenesis of lysosomes. The total protein expression of transcription factor EB (TFEB) as well as that in cytoplasm and nucleus were detected by Western blotting. Confocal laser scanning microscope (CLSM) was used to observe the nuclear translocation of TFEB. The PDLSCs were treated with small interfering RNA (siRNA) technology to knock down the expression levels of TFEB gene with or without PA treatment. Western blotting was used to analyze the expressions of autophagy-related proteins Beclin1 and microtubule-associated protein 1 light chain 3 (LC3B), as well as osteogenic-related proteins runt-related transcription factor 2 (RUNX2), ALP, and osteocalcin in PDLSCs.Results:Compared with the control group, the osteogenic-related and autophagy-related genes showed differential expression in PDLSCs after PA treatment ( P<0.05). The mRNA expression levels of osteogenic-related genes RUNX2 (2.32±0.15) and collagen type Ⅰ alpha 1 (COL1α1) (1.80±0.18), as well as the autophagy related genes LC3B (1.87±0.08) and Beclin1 (1.63±0.08) were significantly increased in the PA group, compared with the control group (1.01±0.16, 1.00±0.10, 1.00±0.07, 1.00±0.06, respectively, all P<0.01). Compared with the control group, the PA group had higher ALP activity, and more autophagosomes and autophagolysosomes observed by TEM. PA promoted the migration of PDLSCs ( P<0.05) and the increased number of lysosomes and the expression of lysosomal associated membrane protein 1 (LAMP1). In the PA group, the relative expression level of total TFEB protein (1.49±0.07) and the nuclear/cytoplasmic expression of TFEB protein (1.52±0.12) were significantly higher than the control group (1.00±0.11, 1.00±0.13, respectively) ( t=6.43, P<0.01; t=5.07, P<0.01). The relative nuclear/cytoplasmic fluorescence intensity of TFEB in the PA group (0.79±0.09) was increased compared with the control group (0.11±0.08) ( t=8.32, P<0.01). Knocking down TFEB significantly reduced the expression of TFEB (1.00±0.15 vs 0.64±0.04), LAMP1 (1.00±0.10 vs 0.69±0.09), Beclin1 (1.00±0.05 vs 0.60±0.05), and LC3B Ⅱ/Ⅰ (1.00±0.06 vs 0.73±0.07) in PDLSCs ( P<0.05, P<0.05, P<0.01, P<0.01). When TFEB gene was knocked down, the expression levels of Beclin1 (1.05±0.11), LC3B Ⅱ/Ⅰ (1.02±0.09), RUNX2 (1.04±0.10), ALP (1.04±0.16), and osteocalcin (1.03±0.15) proteins were significantly decreased in the PA group compared with the pre-knockdown period (1.28±0.03, 1.44±0.11, 1.38±0.11, 1.62±0.11, 1.65±0.17, respectively) ( P<0.05, P<0.01, P<0.05, P<0.01, and P<0.01, respectively). Conclusions:PA promotes the osteogenic differentiation of PDLSCs through inducing the expression and nuclear translocation of TFEB and activating the autophagy-lysosome pathway.

The molar anchorage control in orthodontic treatment is a key concern of clinicians and a hot spot in the field of orthodontic clinical research.Good molar anchorage control is a prerequisite for the success of orthodontic treatment.In recent years,clear aligner treatment has been favored by orthodontists and patients because of its aesthetics,comfort and other advantages.However,the unique biomechanical mechanism of clear aligner system has brought new changes and challenges for dentists to understand the anchorage con-trol in orthodontics.This article provides a systematic review of the research methodology,clinical efficacy and enhanced strategy of mo-lar anchorage control in clear aligner treatment,with the aim to provide a reference for the clinical research and technical development of molar anchorage control in clear aligner treatment.

Objective Visual electrophysiology and optical correlation tomography angiography(OCTA)were used to investigate differences in preoperative retinal function in patients with type 2 diabetic cataract(DC)without obvious retinopathy(NDR)and to determine the clinical application of whole-process blood glucose man-agement(WBGM)for improving postoperative vision in DC patients.Methods This study investigated the preop-erative and postoperative visual electrophysiology(N75,P100,photopic FERG,and scotopic FERG),peripapil-lary retinal nerve fiber layer(pRNFL)and peripapillary capillary vessel density(ppVD)data,as well as trends in these data changes during blood glucose management intervention.Results As the course of T2DM progressed,FBG and HbA1c increased,the N75 and P100 lategraduancy periods of patients gradually lengthened,and the photopic FERG,scotopic FERG,pRNFL,and ppVD values decreased at each postoperative time point.At the same time,the best corrected visual acuity(BCVA)of patients after surgery gradually decreased(P<0.05).Compared with that at 1 week after surgery,the BCVA of Group A(without whole-process blood glucose manage-ment)gradually increased at 1 month and 3 months after surgery but showed a downward trend at 1 year after sur-gery.The BCVA of Group B(with whole-process blood glucose management)gradually stabilized at 1 month after surgery,and at all time points after surgery,the BCVA of Group B was better than that of Group A.The results showed that N75 and P100 in Group A were greater than those in Group B,while the photopic and scotopic FERG,pRNFL,and ppVD(%)in Group A were lower than those in Group B.In addition,N75 and P100 in Group A showed a gradual prolongation trend at various time points after surgery,while photopic FERG,scotopic FERG,pRNFL,and ppVD(%)showed a gradually decreasing trend.However,the above data in Group B gradu-ally stabilized at 3 months after DC surgery,approaching the preoperative level of the group(P<0.05).In the state of whole blood glucose management,although N75 and P100 both reached their longest durations at 1 week af-ter surgery,N75,P100,photopic FERG,scotopic FERG,and pRNFL showed a gradually decreasing trend at 1 month and 3 months after surgery,while ppVD(%)gradually increased(P<0.05).At various time points from 3 months to 1 year after surgery,the overall trend of the above indicators remained stable and close to the preoperative values(P>0.05).Conclusion According to the results of the quantitative analysis of visual electrophysiology and OCTA,in DC patients without obvious retinopathy and with the worsening of diabetes,retinal function decreased,but whole-process blood glucose management effectively restored retinal function and improved visual quality after surgery.

Objective:To understand the current situation of fear of dementia among the elderly in Changsha and its related factors in order to provide empirical evidence for lowering the level of dementia fear among the elderly and formulating effective strategies.Methods:From July to September 2022, 300 elderly people living in communities in Changsha were surveyed using a random sampling method.Data were collected via a questionnaire for general information, the Fear of Dementia Scale, the Social Support Rating Scale, and the Generalized Anxiety Disorder Scale, and multiple linear regression was used to analyze related factors for fear of dementia in the elderly.Results:For elderly people in Changsha, the fear of dementia score was 46.00(33.25, 59.00), the social support score was 40.00(34.00, 44.75), and the generalized anxiety disorder score was 3.00(2.00, 4.00).According to analysis by Spearman's correlation, the level of fear of dementia among the elderly in Changsha was positively correlated to the level of generalized anxiety( r=0.232, P<0.01)and negatively correlated to the level of social support( r=-0.226, P<0.01).Multiple linear regression analysis revealed that level of education( β=-2.385, t=-3.201, P=0.002), family history of dementia( β=10.801, t=4.151, P<0.001), frequency of physical examination( β=-2.601, t=-3.497, P=0.001), and social support( β=-0.347, t=-3.093, P=0.002)were related factors for fear of dementia in the elderly in Changsha. Conclusions:Fear of dementia among the elderly in Changsha is at a moderate level, and there is no widespread generalized anxiety.Family history of dementia, education level, frequency of physical examination, and level of social support are relevant factors for fear of dementia.To lessen the level of fear of dementia, specific intervention methods should be formulated according to the relevant factors.

Objective This research was to evaluate the integrity of visual pathways in patients with Parkinson disease(PD)by visual evoked potential(VEP),especially those with visual hallucinations.Methods A total of 76 PD patients were enrolled in this study.According to the presence or absence of visual hallucinations,they were divided into two groups:24 patients with visual hallucinations and 52 patients without visual hallucinations.At the same time,22 sex-and age-matched healthy controls were selected.All subjects underwent VEP test,and Unified Parkinson's Disease Rating Scale(UPDRS),Hoehn&Yahr stage(H-Y stage)and Mini-mental State Examination(MMSE)were performed for PD patients.Results The latencies of N75,P100 and N135(88.26±10.47)ms,(118.48±8.53)ms,(144.71±9.48)ms were significantly longer in PD patients with visual hallucinations than in those without visual hallucinations[(79.00±6.96)ms,(108.60±7.01)ms,(135.95±8.21)ms](P<0.001).However,the amplitudes of N75-P100 and N135-P100[4.35(2.73,7.30)μV]、[6.40(4.15,9.90)μV]were significantly lower in PD patients with visual hallucinations than in those without visual hallucinations[7.10(5.28,9.98)μV]、[9.05(6.30,12.60)μV](P<0.001,P=0.037).Correlation analysis showed that P100 latency was positively correlated with H-Y stage,UPDRS-I,UPDRS-II,and UPDRS-III scores(r=0.537,P=0.007),(r=0.635,P=0.001),(r=0.594,P=0.004)and(r=0.558,P=0.005)in PD visual hallucinations group.Conclusion The integrity of the visual pathway is impaired in PD patients with visual hallucinations.As the progression of the disease,the impairment of visual pathway may be further deteriorated,which may extend beyond the upper pathways of visual pathway to the brain.

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.