Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes

BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

Clinical efficacy of magnetic vibration magnetoelectric therapy in the treatment of chronic prostatitischronic pelvic pain syndrome

BACKGROUND The prominent symptoms of chronic pelvic pain syndrome(CPPS)are urogenital pain,lower urinary tract symptoms,psychological problems,and sexual dysfunction.Traditional pharmacological treatments have poor efficacy and more untoward reaction and complications.Magnetic vibration magnetoelectric therapy is a non-invasive form of physiotherapy.Nevertheless,its effectiveness in improving urinary discomfort and relieving pain in patients requires further exploration.AIM To investigate the clinical efficacy of the magnetic vibration magnetoelectric therapy instrument in the treatment of chronic prostatitis(CP)/CPPS.METHODS Seventy patients with CP/CPPS were collected from the outpatient clinic and ward of the Department of Male Medicine,Jiangsu Province Hospital of Traditional Chinese Medicine,and were treated with magnetic vibration magnetoelectric therapy once a day for a period of 14 d.National Institutes of healthchronic prostatitis symptom index(NIH-CPSI),international index of erectile function 5(IIEF-5),premature ejaculation diagnostic tool(PEDT),generalized anxiety disorder(GAD),patient health questionnaire,the pain catastrophizing scale(PCS)and traditional Chinese medicine syndrome(TCMS)scores were performed before and after treatment.RESULTS The total effective rate of treatment was 58.5%,and the total NIH-CPSI score,pain symptoms,voiding symptoms,quality of life,IIEF-5,PEDT,GAD,PCS and TCMS scores all decreased significantly(P<0.05).CONCLUSION Magnetic vibration magnetotherapy is effective in improving urinary discomfort,relieving pain,improving quality of life,improving sexual dysfunction and relieving negative emotions such as anxiety in patients with CP/CPPS.

Research Progress of Drug Therapy for Diabetes

Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.

Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

Minimally invasive interventional therapy for pain

Pain interventional therapy,known as the most promising medical technology in the 21st century,refers to clinical treatment technology based on neuroanatomy,neuroimaging,and nerve block technology to treat pain diseases.Compared with traditional destructive surgery,interventional pain therapy is considered a better and more economical choice of treatment.In recent years,a variety of minimally invasive pain interventional therapy techniques,such as neuroregulation,spinal cord electrical stimulation,intervertebral disc ablation,and intrasheath drug infusion systems,have provided effective solutions for the treatment of patients with post-herpetic neuralgia,complex regional pain syndrome,cervical/lumbar disc herniation,and refractory cancer pain.

Ionizable drug delivery systems for efficient and selective gene therapy

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.

Effects of individual shock wave therapy vs celecoxib on hip pain caused by femoral head necrosis

BACKGROUND Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head(ONFH),although significant adverse reactions often follow long-term use.Extracorporeal shock wave therapy(ESWT)can delay the progression of ONFH,alleviate the pain and functional limitations it causes,and avoid the adverse effects of celecoxib.AIM To investigate the effects of individual ESWT,a treatment alternative to the use of celecoxib,in alleviating pain and dysfunction caused by ONFH.METHODS This was a randomized,controlled,double-blinded,non-inferiority trial.We examined 80 patients for eligibility in this study;8 patients were excluded based on inclusion and exclusion criteria.A total of 72 subjects with ONFH were randomly assigned to group A(n=36;celecoxib+alendronate+sham-placebo shock wave)or group B(n=36;individual focused shock wave[ESWT based on magnetic resonance imaging three-dimensional(MRI-3D)reconstruction]+alendronate).The outcomes were assessed at baseline,at the end of treatment,and at an 8-wk follow-up.The primary outcome measure was treatment efficiency after 2 wk of intervention using the Harris hip score(HHS)(improvement of 10 points or more from the baseline was deemed sufficient).Secondary outcome measures were post-treatment HHS,visual analog scale(VAS),and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores.RESULTS After treatment,the pain treatment efficiency of group B was greater than that of group A(69%vs 51%;95%CI:4.56%to 40.56%),with non-inferiority thresholds of-4.56%and-10%,respectively.Furthermore,the HHS,WOMAC,and VAS scores in group B dramatically improved during the follow-up period as compared to those in group A(P<0.001).After therapy,the VAS and WOMAC in group A were significantly improved from the 2nd to 8th wk(P<0.001),although HHS was only significantly altered at the 2 wk point(P<0.001).On the 1st d and 2nd wk after treatment,HHS and VAS scores were different between groups,with the difference in HHS lasting until week 4.Neither group had severe complications such as skin ulcer infection or lower limb motorsensory disturbance.CONCLUSION Individual shock wave therapy(ESWT)based on MRI-3D reconstruction was not inferior to celecoxib in managing hip pain and restrictions associated with ONFH.

Instrumented assisted soft tissue mobilization vs extracorporeal shock wave therapy in treatment of myofascial pain syndrome

BACKGROUND Active myofascial trigger points(TrPs)often occur in the upper region of the upper trapezius(UT)muscle.These TrPs can be a significant source of neck,shoulder,and upper back pain and headaches.These TrPs and their related pain and disability can adversely affect an individual’s everyday routine functioning,work-related productivity,and general quality of life.AIM To investigate the effects of instrument assisted soft tissue mobilization(IASTM)vs extracorporeal shock wave therapy(ESWT)on the TrPs of the UT muscle.METHODS A randomized,single-blind,comparative clinical study was conducted at the Medical Center of the Egyptian Railway Station in Cairo.Forty patients(28 females and 12 males),aged between 20-years-old and 40-years-old,with active myofascial TrPs in the UT muscle were randomly assigned to two equal groups(A and B).Group A received IASTM,while group B received ESWT.Each group was treated twice weekly for 2 weeks.Both groups received muscle energy technique for the UT muscle.Patients were evaluated twice(pre-and posttreatment)for pain intensity using the visual analogue scale and for pain pressure threshold(PPT)using a pressure algometer.RESULTS Comparing the pre-and post-treatment mean values for all variables for group A,there were significant differences in pain intensity for TrP1 and TrP2(P=0.0001)and PPT for TrP1(P=0.0002)and TrP2(P=0.0001).Also,for group B,there were significant differences between the pre-and post-treatment pain intensity for TrP1 and TrP2 and PPT for TrP1 and TrP2(P=0.0001).There were no significant differences between the two groups in the post-treatment mean values of pain intensity for TrP1(P=0.9)and TrP2(P=0.76)and PPT for TrP1(P=0.09)and for TrP2(P=0.91).CONCLUSION IASTM and ESWT are effective methods for improving pain and PPT in patients with UT muscle TrPs.There is no significant difference between either treatment method.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province,China,2014–2020

Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Virtual Reality as an Adjunct to Ketamine Infusion Therapy Increases Patient Satisfaction in the Management of Chronic Pain and Depression: A Retrospective Pilot Study

The management of patients with concomitant chronic pain (CP) and Major Depressive Disorder (MDD) remains challenging for clinicians. Current chronic pharmacologic management is often unsuccessful, or has intolerable side effects to the patients. While not restricted to patients with chronic pain, these patients are often diagnosed with depression, presenting with symptoms such as poor mood, anhedonia, and altered cognitive processes. It is estimated that a substantial proportion of treated patients do not derive a substantive benefit from traditional pharmacological treatments for depression. The present study involved a retrospective review of cases, exploring the patient-reported satisfaction with and tolerability of a novel use of virtual reality (VR), coined KVR, as an adjunct to intravenous ketamine infusion therapies. Specifically, the ketamine-virtual reality protocol was employed as a potential adjunctive intervention for patients suffering from chronic pain and depression. Visual Analog Scores (VAS) associated with pain were significantly lower on the third than on the first assessment day. Montgomery-?sberg Depression Rating Scale (MADRS) scores improved following infusion and across days (i.e., sessions). Lastly, 2/3 of patients preferred the use of VR with their ketamine infusion. The results are considered in terms of implementing prospective studies to examine whether the combination therapies have a synergistic benefit and the nature and magnitude of clinically meaningful treatment effects, if any.

Efficacy and safety of thermobalancing therapy with Dr Allen’s Device for chronic low back pain:A randomised controlled trial

BACKGROUND Lumbar disc herniation and non-specific low back pain are common conditions that seriously affect patients’health-related quality of life(HRQoL).Although empirical evidence has demonstrated that novel Thermobalancing therapy and Dr Allen’s Device can relieve chronic low back pain,there have been no randomised controlled trials for these indications.AIM To evaluate the efficacy of Dr Allen’s Device in lumbar disc herniation(LDH)and non-specific low back pain(NSLBP).METHODS A randomised clinical trial was conducted investigating 55 patients with chronic low back pain due to LDH(n=28)or NSLBP(n=27),out of which 15 were randomly assigned to the control group and 40 were assigned to the treatment group.The intervention was treatment with Dr Allen’s Device for 3 mo.Changes in HRQoL were assessed using the Numerical Pain Rating Scale and the Japanese Orthopedic Association Back Pain Questionnaire.RESULTS Thermobalancing therapy with Dr Allen’s Device showed a significant reduction in pain in the treatment group(P<0.001),with no recorded adverse effects.Both pain assessment scales showed a significant improvement in patients’perception of pain indicating improvement in HRQoL.CONCLUSION The out-of-hospital use of Thermobalancing therapy with Dr Allen’s Device for Low Back Treatment relieves chronic low back pain significantly and without adverse effects,improves the level of activity and HRQoL among patients with LDH and NSLBP.This study demonstrates the importance of this safe first-line therapy that can be used for effective at-home management of chronic low back pain.

Spa therapy relieves knee and shoulder pain:a randomized controlled trial

Objective:To study the effect of spa therapy on relieving knee and shoulder pain.Methods:Participants were randomized to an intervention group(n=26)or a control group(n=23).The intervention group received the hot spring intervention program(1-2 times a day for two weeks),while the control group didn’t receive any intervention.Primary outcomes were assessed by the Western Ontario and McMaster University Osteoarthritis Index(WOMAC)and Shoulder Pain and Disability Index(SPADI).Secondary outcomes were assessed by general physical symptoms and Short Form-36(SF-36)health survey.Results:All parameters before intervention were homogenous between the groups.At baseline,there was no significant difference in WOMAC and SPADI index between the two groups,but there was a statistically significant difference in blurred vision,which was worse in the intervention group than in the control group(P<0.05).After intervention,general physical symptoms were relieved significantly in the intervention group compared with the control group(P<0.05).WOMAC index,SPADI index,social functioning,and general physical symptoms were relieved significantly after intervention in the intervention group(P<0.05).There is a significant difference in the blurred vision before and after the comparison of the control group(P<0.05).Conclusion:Spa therapy may relieve knee and shoulder pain and improve general physical symptoms and quality of life.

Application of Wax Therapy in Pain Care of Patients with Rheumatoid Arthritis

Objective: To investigate the effect of wax therapy in pain care of patients with rheumatoid arthritis. Methods: Convenience sampling method was used to select inpatients with rheumatoid arthritis admitted to the rheumatology and immunology department of a 3A hospital in Jingzhou City. 75 patients from January 2021 to June 2021 were selected as the control group, and 75 patients from January 2022 to June 2022 were selected as the observation group. The control group was given routine nursing, and the observation group was implemented wax therapy nursing on the basis of the control group. The relief of clinical symptoms (morning stiffness time, pain score) and quality of life score of the two groups were observed. Results: After intervention, there was statistical significance between the two groups (P Conclusion: Wax therapy can improve the time of morning stiffness, the degree of pain and the quality of life of patients with rheumatoid arthritis.

Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

MATHEMATICAL MODELING AND BIFURCATION ANALYSIS FOR A BIOLOGICAL MECHANISM OF CANCER DRUG RESISTANCE

Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.

Percutaneous cervical cordotomy for managing refractory pain in a patient with a Pancoast tumor:A case report

BACKGROUND According to the World Health Organization analgesic ladder,cancer-related pain generally begins with pharmacotherapy in a stepwise approach.Nevertheless,some patients continue to experience poorly controlled pain despite medications,particularly when considering adverse effects and self-care quality.Percutaneous cervical cordotomy is an alternative interventional procedure for unremitting unilateral intractable cancer-related pain.CASE SUMMARY The patient was diagnosed with lung cancer with destruction of the brachial plexus and ribs.For 2 mo,the patient experienced progressive severe weakness and pain in the right upper extremity.Notably,the pain intensity reached an extreme level,particularly when lying supine,even under heavy sedation.This heightened pain response posed a significant challenge;as a result,the patient was unable to undergo further evaluation through magnetic resonance imaging.Ultimately,he underwent percutaneous cervical cordotomy for symptom relief,resulting in complete resolution of right arm pain.After a 3-mo follow-up,the pain did not recur,and only a flurbiprofen local patch was required for mild scapular tightness.CONCLUSION Cordotomy,under careful patient selection,appears to enhance the quality of life of patients with unilateral cancerrelated pain.

Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.

Advances in extracellular vesicle-based combination therapies for spinal cord injury

Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.

The dorsal root ganglion as a target for neurorestoration in neuropathic pain

Neuropathic pain is a severe and chronic condition widely found in the general population.The reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in patients.During the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical stimulation.Furthermore,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative therapies.Here,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic pain.More importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

Prognostic characterization of copper death-related immune checkpoint genes and analysis of immunologic and pharmacologic therapy in bladder cancer

Objective:Copper death-induced tumor cell death and immune checkpoint blockade therapy are highly selective.Combining their advantages and understanding their characteristics in bladder cancer is very important for the development of new targeted therapy.The identification of bladder cancer by screening the characteristic genes of copper death-related immune checkpoints provide a theoretical basis for the selection of adjuvant treatment options and the application of new targets.Methods:The expression samples of normal bladder tissue and bladder cancer were obtained from TCGA and GEO databases,and 13 cop-per death genes and 79 immune checkpoint genes were extracted from previous studies.The mRNA expression of prognostic genes was verified by qPCR.The copper death-related immune checkpoint genes were screened by correlation analysis to construct a prognostic model,and the differences in the efficacy of immunotherapy and chemotherapy between the high-risk group and the low-risk group were evaluated.Results:A prognostic model consisting of BTNL9,CD160,TNFRSF14 and TNFRSF18 was constructed.Its reliable predictive ability was proved in both databases,and qPCR showed that the expression levels of the four genes were significantly different between the normal group and the cancer cell group.The effect of immunotherapy in the lowrisk group was better than that in the high-risk group.Patients in the high-risk group had better chemotherapy efficacy.Conclusion:The copper death-related immune checkpoint gene model can accurately predict the prognosis of patients.Drug and immune analysis provide a basis for clinical treatment,and the discovery of potential targets provides a new solution for clinical decision-making.