Objective:To identify and validate the key genes of ferroptosis in phospholipase A2 receptor (PLA2R) associated membranous nephropathy through bioinformatics analysis and in vitro experiments, and to explore the potential role of ferroptosis in PLA2R associated membranous nephropathy (PMN). Methods:The GSE115857 dataset obtained by retrieving the Gene Expression Omnibus (GEO) database and the ferroptosis-related genes obtained by retrieving the FerrDb database were intersected. The intersected genes were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key ferroptosis genes associated with PMN were identified by intersecting genes selected using support vector machines-recursive feature elimination and least absolute shrinkage and selection operator regression. The results were validate by real-time PCR, cell counting kit-8, Western blotting and immunofluorescence in human renal podocyte line AB 8/13 from both the control group and model group.Results:A total of 25 genes related to ferroptosis of PMN were obtained, and GO and KEGG analysis showed that these genes were mainly involved in cell ferroptosis metabolism. The key ferroptosis genes of PMN obtained by machine learning method were activating transcription factor 3 ( ATF3) and coiled coil domain containing 6 ( CCDC6). The results of in vitro experiments showed that the human renal podocyte line AB 8/13 in the model group was significantly deformed and retracted compared with the control group. The surface area density of foot processes was significantly reduced, and the podocyte cytoskeleton was allosteric. The morphology of F-actin was disordered and the expression of synaptopodin was decreased. The cell proliferation activity was significantly decreased ( P<0.05). The expression of PLA2R protein was increased ( P<0.05), and the expression of GPX4 protein was decreased ( P<0.01). The protein and mRNA levels of ATF3 and CCDC6 were significantly up-regulated (all P<0.05). Conclusions:Ferroptosis may be one of the key mechanisms in the occurrence and development of PMN. In vitro experiments show that ATF3 and CCDC6 are the key genes in the ferroptosis of PMN podocytes, which provides new insights and ideas for the pathogenesis of PMN.

Liver Cancer is a prevalent malignant tumor worldwide,with various treatment options available. Among these, ablation therapy holds a significant role in liver cancer treatment due to its minimally invasive nature and lower complication rate. This article reviews the indications and contraindications of liver cancer ablation,the basic principles of different ablation techniques,and their advantages and limitations in clinical applications for liver cancer. Each ablation technique possesses unique characteristics regarding therapeutic efficacy,application scope,and complication profiles,necessitating the selection of the most appropriate approach tailored to the patient′s specific condition and tumor attributes. Furthermore,this article also discusses the potential role of ablation therapy in multidisciplinary treatment,highlighting its synergistic application with liver transplantation,interventional therapy,and immunotargeted therapy to significantly improve outcomes for unresectable liver cancer. Specifically,ablation therapy can induce an anti-tumor immune response by locally destroying the tumor,offering a potential application prospect for combining ablation with immunotherapy. Looking forward,with advances in nanotechnology,artificial intelligence,and image-guided techniques,ablation therapy is expected to progress towards higher precision,personalization,and safety,offering optimized treatment options for liver cancer patients.

Objective:To explore the characteristics of T cells and natural killer (NK) cells in cerebrospinal fluid of patients with multiple sclerosis (MS).Methods:Cerebrospinal fluids from patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls attending the Second Hospital of Lanzhou University from January 2023 to October 2024 were collected and analyzed by single-cell RNA sequencing (scRNA-seq) and flow cytometry, and T and NK cell characteristics were summarized and compared in the two groups. The proposed time-series analysis was used to explore the differentiation trajectories of T cells and NK cells.Results:A total of 3 patients with RRMS and 3 healthy controls underwent scRNA-seq, and 6 patients with RRMS and 4 healthy controls underwent flow cytometry. The composition of cerebrospinal fluid T and NK cell subtypes was similar in the RRMS group and the healthy control group, but the proportion of the cell subtypes differed. The RRMS group exhibited significantly higher frequencies of CD4 +Naive T- IL7R [1 529/9 055(16.89%) vs 1 423/9 910(14.36%), χ2=22.980, P<0.001], CD4 +Naive T- CCR7 [1 573/9 055(17.37%) vs 948/9 910(9.57%), χ2=250.114, P<0.001], and CD4 +Naive T- LTB [1 369/9 055(15.12%) vs 1 079/9 910(10.89%), χ2=75.336, P<0.001] subsets compared to controls. Conversely, the control group demonstrated greater proportions of CD4 +Th1- GZMA [1 255/9 910(12.66%) vs 719/9 055(7.94%), χ2=113.213, P<0.001] and CD8 +Tem- GZMK cells [1 607/9 910(16.22%) vs 1 232/9 055(13.61%), χ2=25.326, P<0.001] than the RRMS group. The transcription factors and gene expression of each T cell subtype were also different between the 2 groups, and CD4 initial T cells and CD8 effector T cells were located at the beginning and the end of the differentiation trajectory, respectively. Conclusions:The cerebrospinal fluid of MS patients is characterized by increased expression of genes involved in T cell differentiation and over-activation of immune cells.

OBJECTIVE To investigate the clinical efficacy and safety of Shouhui tongbian capsule combined with linaclotide in the treatment of constipation-predominant irritable bowel syndrome （IBS-C）. METHODS A total of 97 IBS-C patients admitted to Nanyang First People’s Hospital between March 2022 and February 2024 were enrolled. Using a random number table method， patients were divided into control group （n＝46） and observation group （n＝51）. On the basis of routine treatment， the control group was given Linaclotide capsules orally， while the observation group received Linaclotide capsules combined with Shouhui tongbian capsule orally. The treatment course for both groups was 4 weeks. Clinical efficacy， Irritable Bowel Syndrome Severity Scale （IBS-SSS）， stool frequency， Bristol Stool Form Scale （BSFS）， Irritable Bowel Syndrome Quality of Life Questionnaire （IBS-QOL） score， gastrointestinal hormone levels， anorectal manometry parameters， and the occurrence of adverse reactions were compared between the two groups. RESULTS Two patients in the control group and three patients in the observation group dropped out due to adverse reactions. The effective rate in the observation group （87.50%） was significantly higher than that in the control group （68.18%）（P＜0.05）. Compared with pre-treatment， both groups showed significant increase in post-treatment stool frequency， BSFS score， serum substance P， and motilin levels. Conversely， IBS-SSS scores， IBS-QOL scores， serum vasoactive intestinal peptide levels， anal-rectal pressure difference， rectal compliance， rectal sensation threshold， and defecation threshold were significantly reduced （P＜0.05）. The observation group demonstrated superior outcomes to the control group （excluding rectal sensation and defecation thresholds， P＜0.05）. No significant difference in the incidence of adverse reactions was observed between the two groups （P＞0.05）. CONCLUSIONS Compared with linaclotide monotherapy， Shouhui tongbian capsule combined with linaclotide improves gastrointestinal hormone function and anorectal manometry parameters in IBS-C patients， alleviates clinical symptoms， improves quality of life， and exhibits favorable safety.

ObjectiveTo observe the clinical efficacy and safety of Mailuoning compound solution in the treatment of hip joint pain via nerve blocks around the hip joint. MethodsFrom March 2015 to March 2019，a total of 136 patients with hip joint pain who met the inclusion criteria were admitted and divided into an observation group and a control group according to the random number table method. Among them，six cases fell off due to failure to complete five treatments，and finally， 130 patients entered clinical observation，with 65 cases in each group. The observation group used Mailuoning compound solution for nerve blocks around the hip joint（including obturator nerve，femoral nerve branch，superior gluteal nerve， and hip fascia）. The control used Mailuoning compound solution for a simple obturator nerve block. The differences in the visual analogue scale （VAS） and Harris score of hip joint of the two groups before and after treatment were observed. Any adverse drug reactions and adverse events during the treatment of the patients were recorded. ResultsThe VAS score of the two groups was significantly decreased after treatment （P<0.01）. The observation group had a more significant decrease compared to the control group（P<0.01）. The total Harris score of hip joint， pain degree，function score， and motion of joint of the two groups were significantly improved after treatment （P<0.01）. Compared with the control group，the improvement in the total Harris score of hip joint， pain degree，and function score was more significant in the observation group （P<0.01）. The clinical efficacy based on the Harris score of hip joint of the two groups was compared. The excellent and good rate of the observation group was 84.62% （55/65）， which was significantly better than that of the control group ［56.92% （37/65）］ （χ²=12.05，P<0.01）. The follow-up results showed that the patients who achieved excellent and good results had stable curative effects and low recurrence rates，and there was no significant difference in recurrence rate between the two groups. Case analysis showed that after treatment of femoral head necrosis，the saccular transparent shadow of the femoral head was significantly reduced，and the number of bone trabeculae increased. The low-density shadow decreased as can be seen on hip X-rays. In patients with hip osteoporosis after treatment，the number of bone trabeculae increased， and the low density shadow reduced. ConclusionThe use of Mailuoning compound solution for nerve blocks around the hip joint gives full play to the synergistic effect of Mailuoning compound solution and nerve block. It can effectively relieve hip joint pain，promote the recovery of hip joint function，reduce the disability rate，and improve the quality of life of patients. Early intervention is an important link in the treatment of hip joint pain diseases，which can effectively control the development of the patient's disease. Mailuoning compound solution is a new idea and method to treat hip joint pain through neuroregulation，which is easy to operate，with high safety and good therapeutic effect. In future studies，a larger sample size is needed，and more in-depth research should be conducted on the imaging changes and mechanisms of action for various hip joint pain diseases.

Liver Cancer is a prevalent malignant tumor worldwide,with various treatment options available. Among these, ablation therapy holds a significant role in liver cancer treatment due to its minimally invasive nature and lower complication rate. This article reviews the indications and contraindications of liver cancer ablation,the basic principles of different ablation techniques,and their advantages and limitations in clinical applications for liver cancer. Each ablation technique possesses unique characteristics regarding therapeutic efficacy,application scope,and complication profiles,necessitating the selection of the most appropriate approach tailored to the patient′s specific condition and tumor attributes. Furthermore,this article also discusses the potential role of ablation therapy in multidisciplinary treatment,highlighting its synergistic application with liver transplantation,interventional therapy,and immunotargeted therapy to significantly improve outcomes for unresectable liver cancer. Specifically,ablation therapy can induce an anti-tumor immune response by locally destroying the tumor,offering a potential application prospect for combining ablation with immunotherapy. Looking forward,with advances in nanotechnology,artificial intelligence,and image-guided techniques,ablation therapy is expected to progress towards higher precision,personalization,and safety,offering optimized treatment options for liver cancer patients.

Objective:To identify and validate the key genes of ferroptosis in phospholipase A2 receptor (PLA2R) associated membranous nephropathy through bioinformatics analysis and in vitro experiments, and to explore the potential role of ferroptosis in PLA2R associated membranous nephropathy (PMN). Methods:The GSE115857 dataset obtained by retrieving the Gene Expression Omnibus (GEO) database and the ferroptosis-related genes obtained by retrieving the FerrDb database were intersected. The intersected genes were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key ferroptosis genes associated with PMN were identified by intersecting genes selected using support vector machines-recursive feature elimination and least absolute shrinkage and selection operator regression. The results were validate by real-time PCR, cell counting kit-8, Western blotting and immunofluorescence in human renal podocyte line AB 8/13 from both the control group and model group.Results:A total of 25 genes related to ferroptosis of PMN were obtained, and GO and KEGG analysis showed that these genes were mainly involved in cell ferroptosis metabolism. The key ferroptosis genes of PMN obtained by machine learning method were activating transcription factor 3 ( ATF3) and coiled coil domain containing 6 ( CCDC6). The results of in vitro experiments showed that the human renal podocyte line AB 8/13 in the model group was significantly deformed and retracted compared with the control group. The surface area density of foot processes was significantly reduced, and the podocyte cytoskeleton was allosteric. The morphology of F-actin was disordered and the expression of synaptopodin was decreased. The cell proliferation activity was significantly decreased ( P<0.05). The expression of PLA2R protein was increased ( P<0.05), and the expression of GPX4 protein was decreased ( P<0.01). The protein and mRNA levels of ATF3 and CCDC6 were significantly up-regulated (all P<0.05). Conclusions:Ferroptosis may be one of the key mechanisms in the occurrence and development of PMN. In vitro experiments show that ATF3 and CCDC6 are the key genes in the ferroptosis of PMN podocytes, which provides new insights and ideas for the pathogenesis of PMN.

Objective:To explore the characteristics of T cells and natural killer (NK) cells in cerebrospinal fluid of patients with multiple sclerosis (MS).Methods:Cerebrospinal fluids from patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls attending the Second Hospital of Lanzhou University from January 2023 to October 2024 were collected and analyzed by single-cell RNA sequencing (scRNA-seq) and flow cytometry, and T and NK cell characteristics were summarized and compared in the two groups. The proposed time-series analysis was used to explore the differentiation trajectories of T cells and NK cells.Results:A total of 3 patients with RRMS and 3 healthy controls underwent scRNA-seq, and 6 patients with RRMS and 4 healthy controls underwent flow cytometry. The composition of cerebrospinal fluid T and NK cell subtypes was similar in the RRMS group and the healthy control group, but the proportion of the cell subtypes differed. The RRMS group exhibited significantly higher frequencies of CD4 +Naive T- IL7R [1 529/9 055(16.89%) vs 1 423/9 910(14.36%), χ2=22.980, P<0.001], CD4 +Naive T- CCR7 [1 573/9 055(17.37%) vs 948/9 910(9.57%), χ2=250.114, P<0.001], and CD4 +Naive T- LTB [1 369/9 055(15.12%) vs 1 079/9 910(10.89%), χ2=75.336, P<0.001] subsets compared to controls. Conversely, the control group demonstrated greater proportions of CD4 +Th1- GZMA [1 255/9 910(12.66%) vs 719/9 055(7.94%), χ2=113.213, P<0.001] and CD8 +Tem- GZMK cells [1 607/9 910(16.22%) vs 1 232/9 055(13.61%), χ2=25.326, P<0.001] than the RRMS group. The transcription factors and gene expression of each T cell subtype were also different between the 2 groups, and CD4 initial T cells and CD8 effector T cells were located at the beginning and the end of the differentiation trajectory, respectively. Conclusions:The cerebrospinal fluid of MS patients is characterized by increased expression of genes involved in T cell differentiation and over-activation of immune cells.

As resident immune cells of central nervous system(CNS),microglia play a key role in immune surveillance and tissue repair.They can be activated by various types of pathological factors to form M1 or M2 phenotype,which mediates neuroinflam-mation or neuroprotective effects.At the same time,when the homeostasis of the microenvironment in which the neuron is located is broken,"signal"molecules are also released to induce microglial activation through ligand-receptor binding.Therefore,the regulation of microglia-neuron connection is of great significance for treatment of nervous system diseases.This article reviews the signaling mole-cules involved in the two-way interaction between microglial cells and neurons,and elucidates the immune mechanisms of microglia-neuron,thus providing a basis for targeted treatment of CNS diseases related to microglia activation.

As the incidence of chronic kidney disease (CKD) increases year by year, the number of patients with CKD is increasing year by year before or during pregnancy. Pregnancy management is increasingly important for patients with kidney disease, and women with CKD face a number of challenges during pregnancy, such as the risk of kidney disease progression, fetal growth restriction, the potential teratogenicity of medications, and an increased risk of complications such as preeclampsia and preterm birth. In order to ensure a good outcome for pregnant women and the fetus, it is necessary for multidisciplinary physicians in the department of nephrology, obstetrics, reproductive health and other departments to assess the risk of pregnancy in patients with CKD in a standardized manner, adjust medication in a timely manner, and closely monitor to detect maternal and fetal complications early, stabilize the patient′s condition, and determine the safest time for pregnancy and delivery.