Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

Objective To explore the anti-inflammatory and analgesic mechanism of Yinlian Tongfeng granules by network pharmacology. Methods Three main active components of Yinlian Tongfeng granules were collected from TCMSP database to predict its effective targets. Based on the network information of active components and targets, the anti-inflammatory and analgesic related targets were established by using protein-protein interaction information. The enrichment analysis of KEGG biological pathway and go function enrichment were carried out to construct the active component-target-signal pathway network and explain the main mechanism of anti-inflammatory and analgesic. Results 37 targets were closely related to anti-inflammation and analgesic effects of Yinlian Tongfeng granules, mainly on Prostaglandin endoperoxide synthase 2(PTGS2), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factors (TNF). The mechanism of action may relate to the regulation of nuclear transcription factor B signaling pathway(NF-κB). Conclusion The study predicted the anti-inflammatory and analgesic mechanism of Yinlian Tongfeng granules, and provided theoretical basis for further verification and interpretation of its mechanism.

Objective:To comprehensively analyze the medical resources and services supply in the cancer field of China.Methods:Data of 2018 were sampled from 41 tertiary public cancer hospitals in China, and the factor analysis method was used to extract common factors in resources or services, scoring respectively. Pearson correlation analysis was used in the collinearity test of the variables of both groups of common factors, while the second-order clustering method was used to analyze characteristic differences between the hospitals, and category difference was compared with t test. Results:Resource evaluation covered the two dimensions of basic resources(medical service and basic assurance resources)and high-end resources(high-end talents and academic resources). Service evaluation covered the two dimensions of medical service assurance(clinical services and basic assurance)and disciplinary sphere of influence(discipline construction and clinical efficiency). The factor of basic manpower and beds was significantly correlated with that of medical service and basic assurance( r=0.811, P<0.001), while the factor of high-end talents and academic resources was significantly correlated with that disciplinary construction and resource efficiency( r=0.906, P<0.001). The second-order cluster analysis found the 41 cancer hospitals as two categories, with the first category of five in Guangdong, Shanghai, Beijing and Tianjin, and the second category of the rest 36 hospitals. Significant differences were found between the two categories in terms of resource scoring, service scoring, high-end resources and disciplinary sphere of influence( P<0.001). Meanwhile, the GDP per capita of the cities in which these hospitals are located also had significant differences( P<0.001). Conclusions:Development of public tertiary cancer hospitals in China was imbalanced, as their differences were mainly found in levels of disciplinary development and efficiency of clinical services, which were closely related to the high-end talents and academic resources of the hospital in question.Furthermore, high quality medical care was mostly located in regions of higher development. The authors recommend to take a balanced consideration of the differences and distribution of cancer care services in China, in terms of performance classification of public hospitals and establishment of regional cancer centers of the country.

Objective To investigate the anti-inflammatory and analgesic effects of the active fractions of Tongfeng granules on rats with arthritis induced by complete Freund's adjuvant. Methods 56 SD rats were randomly divided into seven groups, blank group, model group, total flavonoids group, total organic acid group, total alkaloid group, Tongfeng granule group and positive control group. Except for the blank group, the remaining 6 groups established joints pathological model of inflammation. 15 days after the successful modeling, intragastric drug administration was continued for 30 days. The swelling of ankle joint, WBC, N%, IL-6, IL-10, TNF-α and the histopathology of joint were measured. Results Comparing with the model group, each effective fraction group of Tongfeng granules, Gout granules and positive control group decreased the ankle joint swelling rate significantly (P<0.01) and reduced fibrous tissue proliferation. There was no significant difference in WBC and N% of neutrophils. They significantly reduce the level of serum IL-6 and TNF-α, and increase the level of IL-10 (P<0.05, P<0.01). Conclusion This study clarifies the anti-inflammatory and analgesic effects of active fractions of Tongfeng granules and provides a basis for further clinical medication and preparation development.

Objective:To explore the application of games combined with speech training in rehabilitation care for language development retardation in high-risk children aged 2 to 5 years.Methods:Totally 190 high-risk children aged 2 to 5 years with language development retardation admitted from January 2016 to December 2018 in Luzhou People's Hospital were selected by convenient sampling, and divided into observation group ( n=95) and control group ( n=95) according to the random number table. Children in the control group received conventional speech training, while children in the observation group received speech training combined with games for 6 months. The effects of rehabilitation training were observed in the two groups, and the speech development quotient of the children was evaluated using the Gesell Developmental Schedules (GDS) . The satisfaction rate to rehabilitation of parents of two groups were compared. Results:After 6 months of training, the effective rates of rehabilitation training were 86.32% (82/95) in the observation group and 73.68% (70/95) in the control group, and the difference was statistically significant ( P<0.05) . The GDS scores were (60.36±8.25) in the observation group and (56.67 ± 7.84) in the control group, and the difference was statistically significant ( P<0.05) . The satisfaction rate of parents of children in the observation group on rehabilitation effect, service attitude, professional skills, and humane care were higher than those in the control group, and the differences between the two groups were statistically significant ( P<0.05) . Conclusions:In high-risk children aged 2 to 5 years with language development retardation, speech training combined with games can improve children's speech development quotient and promote their rehabilitation.

Objective: A retrospective research was made to summarize the clinical characteristics, treatment methods, results of the adult cases with sagittal fracture of mandibular condyle (SFMC). Methods: One hundred and fifty-one cases of hospitalized patients were enrolled. The age, sex, etiology, level of fracture, degree of displacement, associated facial fractures, treatment methods and results were retrospectively analyzed. Results: The patient′s age ranged from 16 to 81 years old, with a median age of 38.5 years. The male to female ratio was 2.97∶1. The most involved age group was 20-29 years old [35.1% (53/151)]. Falls [53.6% (81/151)] were the most common cause. According to the classification of He (2009) and Duan (2011), the most common type of SFMC was type A [60.5% (130/215)] and the displacement type [80.9% (174/215)]. Eighty-six point zero percent (185/215) of SFMC were treated by surgery. The surgical rates of type A, B and M fractures were 91.5% (119/130), 79.6% (43/54) and 88.5% (23/26), with significant differences between the groups (P<0.05). The surgical rates of the displacement and dislocation type were 89.7% and 100%, with significant differences. The differences between the fixations of type A, type B and type M fractures were statistically significant. The follow-up results showed that, 78.7% (59/75) of patients treated with surgery had normal occlusion, no joint symptoms and no limited mandibular movement. Patients treated with conservative therapy had good occlusion and an average maximum mouth opening of 36.25 mm with malunion occurred in 5/6 of the condyles. Conclusions Under appropriate surgical indications, surgical treatment of SFMCs could achieve significantly better outcomes than conservative treatment.

Objective A retrospective research was made to summarize the clinical characteristics, treatment methods, results of the adult cases with sagittal fracture of mandibular condyle (SFMC). Methods One hundred and fifty-one cases of hospitalized patients were enrolled. The age, sex, etiology, level of fracture, degree of displacement, associated facial fractures, treatment methods and results were retrospectively analyzed. Results The patient′s age ranged from 16 to 81 years old, with a median age of 38.5 years. The male to female ratio was 2.97∶1. The most involved age group was 20?29 years old [35.1% (53/151)]. Falls [53.6% (81/151)] were the most common cause. According to the classification of He (2009) and Duan (2011), the most common type of SFMC was type A [60.5% (130/215)] and the displacement type [80.9% (174/215)]. Eighty-six point zero percent (185/215) of SFMC were treated by surgery. The surgical rates of type A, B and M fractures were 91.5% (119/130), 79.6% (43/54) and 88.5% (23/26), with significant differences between the groups (P＜0.05). The surgical rates of the displacement and dislocation type were 89.7% and 100%, with significant differences. The differences between the fixations of type A, type B and type M fractures were statistically significant. The follow?up results showed that, 78.7% (59/75) of patients treated with surgery had normal occlusion, no joint symptoms and no limited mandibular movement. Patients treated with conservative therapy had good occlusion and an average maximum mouth opening of 36.25 mm with malunion occurred in 5/6 of the condyles. Conclusions Under appropriate surgical indications, surgical treatment of SFMCs could achieve significantly better outcomes than conservative treatment.

Objective To observe the effects of different Mongolian acupuncture methods on neurons form in frontal lobe and NO-cGMP signaling pathways in rats with chronic stress depression; To explore biological mechanism of different Mongolian acupuncture methods for depression.Methods The male SD rats were randomly divided into control group, model group, fluoxetine group, Mongolian silver acupuncture group, Mongolian acupuncture three modulation methods group, and the combination of acupuncture with fluoxetine group (8 rats in each group). Except for control group, other rats were kept alone. Rats receive different treatment 1 hour before stimulations. Behavior changes were observed after 28 days. Hippocampus and frontal lobe tissues were collected. Frontal lobe neurons form changes were observed through different dyeing methods. The content of NO-cGMP was detected by radioimmunoassay and nitrate reductase method.Results Results of Nissl's staining showed that the neuronal pyramidal cells in the frontal lobe of model group rats arranged disorderedly, morphology was not intact and the number was obviously reduced. Nissl's staining got shallow and the most were blurry. The form of the frontal lobe neurons in Mongolian acupuncture three modulation methods group and Mongolian acupuncture group were good, Nissl's staining was dark blue. HE staining results showed that cytomembrane of frontal lobe neurons in model group rats ruptured, and structure was not clear. some cells fell off and formed into cavities. In Mongolian acupuncture three modulation methods group and Mongolian silver acupuncture group, the frontal lobe cells arranged regularly, cellular level was rich, and the nerve cell membrane was complete. The content of NO-cGMP in frontal lobe and hippocampus tissues was significantly elevated in model group. Mongolian acupuncture, Mongolian acupuncture three modulation methods, fluoxetine, and the combination of acupuncture with fluoxetine treatments all could reverse the changes.Conclusion Different Mongolian acupuncture methods may treat depression through regulating and controlling the expression of NO-cGMP.

To study the abnormal distribution of type Ⅳ collagen and laminin chains in glomerular basement membrane (GBM) in membranous nephropathy (MN).Methods 52 cases of MN were collected and staged according to electron microscopic morphological characteristics,and 10 cases of kidney tissues of minimal change disease were used as normal GBM control.Distribution pattern of or5 (Ⅳ) chain,laminin α5and β2 chains,and laminin α2 and β1 chains were detected using immunofluorescence method.Results In minimal change disease,α5 (Ⅳ) chain,laminin α5 and β2 chains all showed continuously linear positive expression along GBM,and laminin α2 and β1 chains were negatively expressed in GBM.In stage Ⅰ MN,α5 (Ⅳ) chain,laminin α.5 and β2 chains all showed continuous linear positive expression along GBM.In stage ⅡMN,the expression of α5 (Ⅳ) chain was increased and showed abundant spikes on the basis of continuous linear positive staining along GBM,and the expression of laminin α5 and β2chains was increased,and segmental spikes were seen on the basis of continuous linear positive staining along GBM.In stage ⅢMN,the expression of α5 (Ⅳ),laminin α5 and β2 chains was also enhanced and segmental double tracks were seen.The expression of laminin α2 chain was negative in GBM in stage ⅠMN,but granular positive expression along GBM was seen in stage Ⅱ and stage Ⅲ MN.No positive expression of laminin β1chain was seen in GBM in different stages in MN.Conclusion The GBM thickness in MN originates not only from intrinsic type Ⅳ collagen chains and laminin chains,but also from laminin α2chain,which only exist in glomerulus mesangium in normal condition.

Objective To analyze the clinical characteristics of children with knee joint diseases and discuss the curative effect of arthroscopy.Methods Eighty-nine children with knee joint diseases in Department of Orthopedics,the First Affiliated Hospital of Xinxiang Medical University from October 2012 to October 2015 were selected,and they were given knee arthroscopic surgery according to the disease types and characteristics,such as meniscal suture,suture plus angioplasty and synovectomy etc.All the symptoms,signs and the joint functions were recorded preoperatively and postoperatively.At the end of follow-up,surgical results were analyzed according to Lysholm score and International Knee Documentation Committee Knee evaluation form (IKDC) classification standard.Results The patients with discoid meniscus tear were the most,accounting for 55.55％ (55/99 knees).All patients were followed up for 6-30 months(the average time was 21 months) to find that all symptoms were relieved or disappeared within 1 year after operation.The outcome was evaluated according to the Tegner knee function:76 knees (76.76％) were markedly effective,16 knees (16.16％) were effective,6 knees (6.06％) were invalid and 1 knee (1.01％) was poor,and the excellent rate was 92.92％.The curative effect was evaluated according to Lysholm knee function score and IKDC score at the last follow-up.The Lysholm score in preoperation [(52.46 ± 4.79) scores] improved to (96.52 ± 3.97) scores in postoperation,and the difference was significant (t =-36.24,P ＜ 0.05);the IKDC score in preoperation [(46.52 ± 10.25) scores] improved to (90.67-± 5.89) scores in postoperation,and the difference was significant (t =-50.69,P ＜ 0.05).There was no joint infection,blood vessel or nerve damage and so on.Conclusions Meniscus tear is common in children with knee joint diseases,and most common is discoid lateral meniscus tear,and arthroscopy can have satisfactory outcome,with no obvious complications.Therefore,arthroscopic surgery is an ideal method for surgical treatment of children with knee joint disease.