Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

In recent years, with the endless emergence of meibomian gland dysfunction(MGD)diagnostic equipment, rich treatment methods, and in-depth clinical and basic research on MGD at home and abroad, the understanding of MGD has entered a new stage. MGD-related dry eye is considered to be the main cause of lipid abnormal dry eye, and its occurrence and development is a chronic and multi-factorial pathological process. This article reviews the pathogenesis, imaging analysis and clinical treatment progress of MGD-related dry eye, in order to provide scientific evidence and ideas for clinical diagnosis and therapy of MGD-related dry eye.

The role of osteoblast(OB)autophagy in regulating bone metabolism is a research hotspot in the field of biomedicine.OB autophagy can regulate osteoporosis(OP)induced by aging,oxidative stress,estrogen deficiency,and glucocorticoids(GCs)by mediating factors such as run and cysteine rich domain containing Beclin-1 interacting protein(RUBCN),silent information regulator of transcription 1(SIRT1),and osteoprotegerin(OPG).OB autophagy can also regulate OP by activating notch receptor(Notch)and forkhead box protein O subfamily(FoxO),up-regulating the expression of osteogenic transcription factors(such as Runx2 and Osterix),and mediating the amp-activated protein kinase(AMPK),mammalian target of rapamycin complex(mTOR),Wnt,and c-Jun n terminal kinase(JNK)pathways to act on OB and osteoclast(OC)differentiation.Exercise is an important means of improving OP,and its molecular mechanism is closely related to the up-regulation of phosphatidylinositol 3 kinase(PI3K),adenosine monophosphate(AMP),tumor necrosis factor-alpha(TNF-α),and SIRT1 expression.These in turn activate key factors or pathways(including AMPK,mTOR,Wnt,PI3K/protein kinase B(Akt)/mTOR,and nuclear transcription factor-KB(NF-κB)),regulate the expression of downstream target genes(β-catenin,mTOR,FoxO3a and B cell lymphoma-2(Bcl-2))to up-regulate the expression of autophagy factors(Beclin-1,autophagy related genes(ATG),and microtubule-associated protein 1 light chain 3(LC3)),and promote OB autophagy to restore the dynamic balance in the body,thereby regulating bone formation and bone resorption and improving OP.The relationships among exercise,OB autophagy and OP,however,remain unclear and there is currently a lack of systematic reviews.Here we review and analyze the mechanism of OB autophagy in relation to exercise-induced improvements in OP,and provide a new theoretical basis and research ideas for the prevention and treatment of OP.

The role of osteoblast(OB)autophagy in regulating bone metabolism is a research hotspot in the field of biomedicine.OB autophagy can regulate osteoporosis(OP)induced by aging,oxidative stress,estrogen deficiency,and glucocorticoids(GCs)by mediating factors such as run and cysteine rich domain containing Beclin-1 interacting protein(RUBCN),silent information regulator of transcription 1(SIRT1),and osteoprotegerin(OPG).OB autophagy can also regulate OP by activating notch receptor(Notch)and forkhead box protein O subfamily(FoxO),up-regulating the expression of osteogenic transcription factors(such as Runx2 and Osterix),and mediating the amp-activated protein kinase(AMPK),mammalian target of rapamycin complex(mTOR),Wnt,and c-Jun n terminal kinase(JNK)pathways to act on OB and osteoclast(OC)differentiation.Exercise is an important means of improving OP,and its molecular mechanism is closely related to the up-regulation of phosphatidylinositol 3 kinase(PI3K),adenosine monophosphate(AMP),tumor necrosis factor-alpha(TNF-α),and SIRT1 expression.These in turn activate key factors or pathways(including AMPK,mTOR,Wnt,PI3K/protein kinase B(Akt)/mTOR,and nuclear transcription factor-KB(NF-κB)),regulate the expression of downstream target genes(β-catenin,mTOR,FoxO3a and B cell lymphoma-2(Bcl-2))to up-regulate the expression of autophagy factors(Beclin-1,autophagy related genes(ATG),and microtubule-associated protein 1 light chain 3(LC3)),and promote OB autophagy to restore the dynamic balance in the body,thereby regulating bone formation and bone resorption and improving OP.The relationships among exercise,OB autophagy and OP,however,remain unclear and there is currently a lack of systematic reviews.Here we review and analyze the mechanism of OB autophagy in relation to exercise-induced improvements in OP,and provide a new theoretical basis and research ideas for the prevention and treatment of OP.

Objective To compare and find an optimal model for predicting the risk of DKD occurrence in patients with type 2 diabetes mellitus(T2DM).Methods A total of 2005 patients with T2DM were enrolled in this study from The Second Hospital of Shijiazhuang City during December 2017 to December 2022.All the subjects were divided into a training set(n=1403)and a validation set(n=602)according to the ratio of 3∶1 by simple random sampling.With the occurrence of DKD as the outcome variablein the training set,important feature variables were screened by LASSO regression.Six different machine learning models were established according to the feature variables,thenthe optimal model was determined by comparison,and anonlinerisk predictor for DKD occurrence was constructed in patients with T2DM.Results Taking the occurrence of DKD as the outcome variable in the training set,the results of LASSO regression analysis showed that the optimal value of the model was 10-fold cross validation lambda.1se=0.01662473,and 15 characteristic variables with nonzero coefficient were screened out to be related to the occurrence of DKD.The data included sex,age,family history of DM,DM duration,LDL-C,HbA1c,WBC,PDW,Scr,urine α1-microglobulin,urine β2-microglobulin,urine microalbumin,hypertension,hypokalemia,and DR.In the training set and validation set,the prediction performance of XGBoost model was better than that of other models(AUC=0.872,0.893,95%CI 0.853～0.891,0.865～0.921),the sensitivity was 0.779,0.863,and the specificity was 0.721,0.758,respectively.The F1 scores were 0.774 and 0.787.DCA analysis showed that the XGBoost model had a greater net benefit and threshold probability.According to the XGBoost model,the online predictor of DKD risk in T2DM patients was laid out,and two patients were selected for application,the results showed that the predictive value of the model was 0.185 in non-DKD patients,and the predictive value was 0.510 in DKD patients.Conclusions The XGBoost model is the best model for predicting the occurrence of DKD in T2DM patients,and an online predictor was successfully built.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective To retrieve,evaluate and summarise the best evidence on screening and management of psychological distress in patients who had ostomy for colorectal cancer.Methods Literatures on psychological distress screening and management in patients undergoing colorectal cancer ostomy were systematically searched across various websites and databases of home and abroad from inception to 20th June,2024 including Cochrane Library,PubMed,Embase,CINAHL,Web of Science,CNKI,Wangfang,VIP,UpToDate,National Guideline Clearing-house,National Comprehensive Cancer Network,the National Institute for Health and Care Excellence,Scottish Intercollegiate Guidelines Network,the International Guideline Collaboration Network,Wound,Ostomy and Continence Nurses Society,World Council of Enterostomal Therapists,Medlive,Chinese Nursing Association.The search aimed to identify evidence on psychological distress screening and management in patients with colorectal cancer and stomas,including guidelines,evidence summaries,expert consensuses,systematic reviews,and Meta-analyses.The search was limited to articles published from the inception of each database to 20th June,2024.The searched literature included guidelines,evidence summary,expert consensus,systematic review,meta-analysis,etc..Two researchers independently evaluated the quality of literature and extracted evidences,as well as checked and integrated the evidences together with a panel of evidence-based research experts.Results A total of 14 articles were included,comprising four guidelines,one expert consensus,two evidence summaries,four meta-analyses and three systematic reviews.The articles encompassed 7 dimensions with a total of 18 pieces of evidence,including one in screening timing,one in screening tools,3 in screening content,3 in drug intervention,3 in self-management,5 in psychological support and 2 in health education.Conclusion The evidence summarised in this study on the screening and management of psychological distress in patients who had ostomy for colorectal cancer is scientifically comprehensive.It provides an evidence-based basis for medical staff in prevention and management of psychological distress in patients.It is necessary to formulate a scientific management plan in clinical practice,according to the specific requirements of departments,the patients and their family members.

OBJECTIVE To investigate the risk factors for carbapenem-resistant gram-negative bacteria(GNB)bloodstream infection(BSI)in patients with hematological malignancies(HMs)and their prognosis,and to devel-op a nomogram prediction model.METHODS A total of 316 patients with HMs and GNB-BSI admitted to the First Affiliated Hospital of Xi'an Jiaotong University from Jan.2017 to Dec.2022 were selected as the training set,and 106 patients admitted from Jan.2023 to Oct.2024 were selected as the validation set.Variables were selected by lasso regression and multifactor logistic regression,and a nomogram model was constructed.The prediction model was internally validated by the receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis(DCA),respectively.RESULTS Granulocytopenia for ≥7 days(OR=14.525),use of cephalosporins/β-lactamase inhibitors within 30 days before BSI(OR=3.510),exposure history of carbapenem antibacterial drug(OR=4.840)and albumin＜30 g/L(OR=2.697)were risk factors for CR-GNB BSI in patients with HMs(P＜0.05).Septic shock(OR=6.934),central venous catheterization(OR=5.586),inappropriate empirical antibac-terial drug therapy(OR=4.744),CR-GNB infection(OR=2.916)and albumin＜30 g/L(OR=3.324)were risk factors for 30-day mortality in patients with HMs and GNB-BSI(P＜0.05).Based on these indicators,two nomogram models were constructed.The areas under the ROC curve(AUC)for the internal validation set were 0.775 and 0.849,respectively.The calibration curves demonstrated high predictive performance for the pre-diction models(P=0.998 and 0.660,respectively),and DCA showed high clinical application value for both models.CONCLUSION The nomogram prediction model constructed in this study based on multifactor analy-sis not only demonstrates good predictive value but also exhibits significant clinical efficacy,aiding in the early i-dentification of high-risk patients for targeted therapy.

BACKGROUND:Through scientific research addressing the effect of calcined deer antler slices on promoting the proliferation of bone marrow mesenchymal stem cells,it aims to provide empirical support for the integration and innovation of traditional Chinese medicine and modern regenerative medicine,and promote the widespread application of traditional Chinese medicine in the treatment of skeletal system diseases.OBJECTIVE:To investigate the effect of calcined deer antler slices on bone marrow mesenchymal stem cell proliferation.METHODS:Different calcination samples were prepared by wrapping deer antler slices with materials such as clay,yellow clay,and salted yellow clay,resulting in seven different samples(clay-cotton cloth,yellow clay-cotton cloth,salted yellow clay-cotton cloth,yellow clay-tin foil,salted yellow clay-tin foil,yellow clay-honey roasted,salted yellow clay-honey roasted antler slices).Water-soluble extract content in deer antler slices was determined before and after calcination.CCK-8 assay was used to evaluate the effects of different aqueous extracts of calcined antler slices on the proliferation activity of bone marrow mesenchymal stem cells.RESULTS AND CONCLUSION:(1)Calcination significantly increased the water-soluble extract content of deer antler slices,with the highest content observed in samples treated with yellow clay and honey.(2)Calcined deer antler slices significantly promoted bone marrow mesenchymal stem cell proliferation,among which the yellow clay-honey roasted deer antler slices have the most significant effect on promoting the proliferation of bone marrow mesenchymal stem cells.

BACKGROUND:With the increasing attention of scholars at home and abroad to children's cervical spine-related diseases,the demand for exploring the anatomical indicators and changes of cervical spine morphology and development in children of different ages is increasing.OBJECTIVE:To explore and analyze the morphological changes of children with different ages and vertebral sequences by measuring the anatomical position indexes of C2-C7 neurocentral synchondrosis in children aged 1-6 years.METHODS:Normal cervical spine CT images were retrospectively collected from 160 children aged 1-6 years at provincial tertiary hospitals.They were divided into six groups according to an age group of 1 year.The raw data of consecutively scanned cervical spine tomography images were imported into Mimics 16.0 software.The positional anatomical indexes of cervical spine segments C2-C7 in coronal and transverse planes were measured and analyzed under the two-dimensional image window by choosing the measurement tools under the toolbar of Measurements.RESULTS AND CONCLUSION:(1)The distance between the two sides of C2-C7 neurocentral synchondrosis and the distance between the left and right sides of neurocentral synchondrosis and the transverse process gradually increased with age.The overall development of vertebrae in each cervical vertebral segment was faster than the ossification of the neurocentral synchondrosis.(2)The cross-sectional angles on both sides of C2-C7 neurocentral synchondrosis gradually increased with age,and the angles between the left and right sides of neurocentral synchondrosis and the anterior and posterior edges of the vertebral body gradually decreased.Both sides of the neurocentral synchondrosis in cervical vertebral segments tended to grow toward the arch site,which mainly promoted the growth and development of the arch.(3)Except for C7,the angle between the coronal planes on both sides of the cervical spine changed little with the descending neurocentral synchondrosis of the cervical spine,and the neurocentral synchondrosis of the cervical spine was more inclined to longitudinal growth and ossification.(4)The neurocentral synchondrosis position changes in C7 were significantly different from those in the rest of the cervical vertebrae.(5)The anatomical indexes of C2-C7 neurocentral synchondrosis position in children have obvious development rules among different ages and vertebral bodies,and these rules are helpful for the clinical diagnosis and treatment of cervical spine diseases in children.