AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.

In order to further standardize the vaccination of kidney transplant candidates and recipients in China, the Branch of Organ Transplantation of Chinese Medical Association has organized experts in kidney transplantation and infectious diseases. Based on the "Vaccination of Solid Organ Transplant Candidates and Recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice", and in combination with the clinical reality of infectious diseases and vaccination after organ transplantation in China, as well as referring to relevant recommendations from home and abroad in recent years, these guidelines are formulated from aspects such as epidemiology, types of vaccines, vaccination principles, target population, and specific vaccine administration. The "Guidelines for Vaccination of Kidney Transplant Candidates and Recipients in China" aims to provide theoretical reference for medical workers in the field of kidney transplantation in China, regarding the vaccination of kidney transplant candidates and recipients. It is expected to better guide the vaccination of kidney transplant candidates and recipients, reduce the risk of postoperative infection, and improve survival outcomes.

Objective: To investigate the efficacy，safety and feasibility of regional lymph node dissection in laparoscopic radical surgery for bladder cancer under the guidance of indocyanine green fluorescence imaging. Methods: A total of 30 patients with muscle invasive bladder cancer (T2/T3NxM0) who volunteered to enter the clinical trial were randomly divided into the indocyanine green imaging guided laparoscopic regional lymph node dissection group (n=15) and the standard pelvic lymph node dissection group (n=15).The number of positive lymph nodes，operation time，intraoperative bleeding volume，incidence of lymph leakage，and tumor recurrence and metastasis rate 2-year after surgery were collected. Results: The number of positive lymph nodes was (4.20±1.66) and (4.60±1.72) respectively in the indocyanine green and standard groups，with no statistically significant difference (P>0.05).There were no statistically significant difference in the tumor recurrence and metastasis rates 2-year after surgery between the two groups (P>0.05).However，the indocyanine green group had shorter operation time，less intraoperative bleeding volume，and lower incidence of lymphatic leakage than the standard group (P<0.05). Conclusion: Indocyanine green fluorescence imaging guided laparoscopic lymph node dissection has comparable clinical efficacy to standard lymph node dissection，but with fewer complications.

Objective To develop an expert consensus on subcutaneous injection for allergen-specific immunotherapy.Methods Relevant domestic and intemational literature was reviewed,and nursing experts who had experiences in subcutaneous injection of allergen-specific immunotherapy were interviewed to form the initial draft of the consensus.A total of 85 experts from 42 hospitals nationwide were invited to participate in discussions.2 rounds of expert consultations,adjustments,revisions,and improvements were made to the initial draft,and an online meeting was held to form the final version of the consensus.The content approved by more than 75％of the expert group is adopted,or it will be discussed or deleted.Results The expert consensus includes operational standards for subcutaneous injection of allergen-specific immunotherapy,identification and management of adverse reactions,and health education.Conclusion The consensus demonstrates strong scientific rigor and practicality,providing guidance for nursing practices in the field of clinical allergology.

Objective:To investigate the central mechanism of moxibustion in treating chronic inflammatory visceral pain(CIVP)and its analgesic effect from the perspective of the p38 mitogen-activated protein kinase(MAPK)/Ets-like transcription factor 1(ELK1)signaling pathway in the spinal cord. Methods:Clean-grade male Sprague-Dawley rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion(HPM)group,a sham-HPM group,a p38 MAPK inhibitor group,and a dimethyl sulfoxide(DMSO)group.CIVP rat models were prepared using an enema mixture of 2,4,6-trinitrobenzene sulfonic acid solution and 50%ethanol.The HPM group was treated with HPM;the sham-HPM group was treated the same as the HPM group,but the moxa cones were not ignited;rats in the p38 MAPK inhibitor group received L5-L6 intrathecal injection of p38 MAPK inhibitor(SB203580);rats in the DMSO group received L5-L6 intrathecal injection of 2%DMSO.Abdominal withdrawal reflex(AWR),mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were used to observe pain-related behaviors in each group.Hematoxylin-eosin staining was used to observe the morphological changes in rat colon tissue.Western blotting and real-time quantitative reverse-transcription polymerase chain reaction were used to detect the phosphorylated protein and mRNA expression of apoptosis signal-regulating kinase 1(ASK1),MAPK kinase(MKK)3/6,p38 MAPK,ELK1,and mitogen and stress-activated protein kinase 1(MSK1)in the spinal cord. Results:Compared with the normal group,CIVP rats had severe colonic inflammatory injuries,and the pathological injury scores increased significantly,along with increased AWR scores under different colorectal distension(CRD)stimulation pressures and decreased MWT and TWL;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,MSK1,ASK1,MKK3,and MKK6 all increased in the spinal cord(P<0.01).After HPM treatment,the colon injuries were repaired,and the pathological injury scores decreased;under different CRD stimulation pressures,the AWR scores decreased,and the MWT and TWL increased;the mRNA and phosphorylated protein expression of p38 MAPK,ELK1,ASK1,and MKK3 in the spinal cord also decreased,with statistically significant differences compared with the model group and the sham-HPM group(P<0.01).There were no significant differences in the above indicators between the HPM group and the p38 MAPK inhibitor group(P>0.05),and the same was true regarding the comparisons between the model group and the DMSO group. Conclusion:HPM exerted analgesic effects via downregulating the mRNA and phosphorylated protein expression of ASK1,MKK3,p38 MAPK,and ELK1 in the spinal cord of CIVP rats.The inhibition of spinal p38 MAPK/ELK1 signaling pathway activation may be one of the mechanisms by which HPM relieves pain in CIVP.

Objective:To explore the therapeutic mechanism of electroacupuncture(EA)in treating Parkinson disease(PD)using Tandem mass tag(TMT)quantitative proteomics technology. Methods:Forty-eight PD patients were randomly divided into a control group and an observation group,with 24 patients in each group.The control group received routine drug treatment,while the observation group received EA in addition to the routine drug treatment.EA was administered for 30 min per session,3 times a week,for a total of 12 weeks.Nine patients from each group were randomly selected to provide peripheral blood serum samples before and after treatment for TMT quantitative proteomics analysis.Differentially expressed proteins between the two groups were compared,and bioinformatics analysis was performed.The screened differentially expressed proteins were validated using enzyme-linked immunosorbent assay(ELISA). Results:In the observation group,scores on the unified Parkinson disease rating scale(UPDRS),UPDRS Ⅱ,and UPDRS Ⅲ were significantly reduced after treatment(P<0.05).In the control group,these scores tended to increase,but the changes were not statistically significant(P>0.05).After treatment,the UPDRS and UPDRS Ⅲ scores in the observation group were significantly lower than those in the control group(P<0.05).The observation group showed 62 differentially expressed proteins,while the control group had 36.Compared to the control group,the observation group had 142 differentially expressed proteins.These proteins were primarily involved in the cyclic adenosine monophosphate(cAMP)signaling pathway,T helper(Th)1 and Th2 cell differentiation,ATP-binding cassette transporter,vascular endothelial growth factor signaling pathway,and high-affinity immunoglobulin E receptor(FcεRI)signaling pathway.ELISA verification indicated that after EA treatment,the levels of α-Synuclein(αSyn)and heat shock protein beta 1(HSPB1)in the observation group were significantly lower than those in the control group(P<0.05),while the regulator of G-protein signaling 10(RGS10)level was significantly higher(P<0.05). Conclusion:EA,combined with routine drug therapy,can significantly improve clinical symptoms of PD,potentially through the regulation of the cAMP signaling pathway and the contents of differentially expressed proteins of αSyn,HSPB1,and RGS10.

Objective:To discuss the factors related to the prognosis in the alpha fetoprotein(AFP)negative hepatocellular carcinoma(HCC)patients,and to construct the nomogram for predicting the survival time of the patients.Methods:The retrospective analysis on data of 2 064 cases of AFP negative HCC patients extracted from the Surveillance,Epidemiology,and End Results(SEER)Database was conducted,and all the patients were divided into training cohort and internal validation cohort at a ratio of 7∶3,and 101 AFP negative HCC patients from the Integrated Traditional Chinese and Western Medicine Hospital in Hunan Province were regarded as the external validation cohort.The univariate Cox regression analysis results were incorporated into the multivariate analysis,and the independent risk factors for the AFP negative HCC patients were obtained by multivariate Cox analysis to build a cancer specific survival(CSS)prognosis nomogram for the AFP negative HCC patients.The predictive efficacy and clinical utility of the nomogram were evaluated by time-dependent receiver operating characteristic curve(ROC),calibration plots,and decision curve analysis(DCA).The total score obtained from the nomogram was used for the risk stratification to compare the degree of risk discrimination between the nomogram and the American Joint Committee on Cancer(AJCC)staging system.Results:Ten independent risk factors were selected by multivariate Cox regression analysis to construct 3-year,4-year,and 5-year CSS prognostic nomograms for the AFP negative HCC patients,including the patient's age,pathological grade,surgical status,radiotherapy status,chemotherapy status,lung metastasis status,tumor size,tumor T stage,tumor M stage,and marital status.The area under curve(AUC)for the 3-year,4-year,and 5-year time-dependent ROC in the training cohort were 0.807(95%CI:0.786-0.828),0.804(95%CI:0.782-0.826),and 0.813(95%CI:0.790-0.835),respectively.In the internal validation cohort,they were 0.776(95%CI:0.743-0.810),0.772(95%CI:0.737-0.808),and 0.789(95%CI:0.752-0.826),and in the external validation cohort,they were 0.773(95%CI:0.677-0.868),0.746(95%CI:0.620-0.872),and 0.736(95%CI:0.577-0.895).The calibration plots verified that the nomogram fitted well with the perfect line.The DCA curve revealed that the net benefit of the nomogram was significatly higer than that of the AJCC staging system at certain probability thresholds compared with AJCC staging,the nomogram had a better ability to identify high-risk individuals.Conclusion:The serum AFP expression is one of the prognostic markers for the HCC patients.For those patients with AFP negative expression in serum,different considerations should be taken.The nomogram model based on multiple risk factors is a promising clinical tool for assessing the CSS in the AFP negative HCC patients.

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

Objective To investigate the efficacy,safety and feasibility of laparoscopic lymph node dissection guided by indocyanine green(ICG)fluorescence imaging.Methods A total of 30 patients with muscle-invasive bladder cancer(MIBC,T2/T3NxM0)who were admitled to the Cangzhou People's Hospital during Mar.2018 and Jun.2022 were included.The lymph nodes were cleared with ICG fluorescence imaging first,and then the remaining lymph nodes were cleared according to the standard pelvic lymph node range.The lymph node positive rate of ICG fluorescence imaging guided laparoscopic lymph node precise dissection and standard pelvic lymph node dissection was analyzed by self-comparison.Results ICG fluorescence imaging guided laparoscopic lymph node precise dissection needed shorter operation time than standard pelvic lymph node dissection[(21.80±6.80)min vs.(47.70±10.73)min,P＜0.05].There was no significant difference in the lymph node positive rate between the two approaches[(11.34±9.06)％vs.(12.36±9.43)％,P＞0.05],but the former approach caused less damage on blood vessels and nerves.Conclusion Indocyanine green fluorescence imaging guided laparoscopic lymph node dissection has comparable efficacy to standard pelvic lymph node dissection,which can reduce ineffective lymph node dissection,shorten the operation time,and reduce the risk of complications.

Objective To investigate the potential value of exosomes derived from rat ectoderm mesenchymal stem cells(EMSCs-exo)for repairing secondary spinal cord injury.Methods EMSCs-exo were obtained using ultracentrifugation from EMSCs isolated from rat nasal mucosa,identified by transmission electron microscope,nanoparticle tracking analysis(NTA),and Western blotting,and quantified using the BCA method.Neonatal rat microglia purified by differential attachment were induced with 100 μg/L lipopolysaccharide(LPS)and treated with 37.5 or 75 mg/L EMSCs-exo.PC12 cells were exposed to 400 μmol/L H2O2 and treated with EMSCs-exo at 37.5 or 75 mg/L.The protein and mRNA expressions of Arg1 and iNOS in the treated cells were determined with Western blotting and qRT-PCR,and the concentrations of IL-6,IL-10,and IGF-1 in the supernatants were measured with ELISA.The viability and apoptosis of PC12 cells were detected using CCK-8 assay and flow cytometry.Results The isolated rat EMSCs showed high expressions of nestin,CD44,CD105,and vimentin.The obtained EMSCs-exo had a typical cup-shaped structure under transmission electron microscope with an average particle size of 142 nm and positivity for CD63,CD81,and TSG101 but not vimentin.In LPS-treated microglia,EMSCs-exo treatment at 75 mg/L significantly increased Arg1 protein level and lowered iNOS protein expression(P<0.05).EMSCs-exo treatment at 75 mg/L,as compared with the lower concentration at 37.5 mg/L,more strongly increased Arg1 mRNA expression and IGF-1 and IL-10 production and decreased iNOS mRNA expression and IL-6 production in LPS-induced microglia,and more effectively promoted cell survival and decreased apoptosis rate of H2O2-induced PC12 cells(P<0.05).Conclusion EMSCs-exo at 75 mg/L can effectively reduce the proportion of M1 microglia and alleviate neuronal apoptosis under oxidative stress to promote neuronal survival,suggesting its potential in controlling secondary spinal cord injury.