Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

ObjectiveTo investigate the correlation among the botanical characteristics， biological characteristics， chemical composition， and medicinal properties and efficacy of traditional Chinese medicines （TCM） from latex-containing plants， so as to strengthen the theory of "identifying symptoms for qualities" and provide a reference for the development and utilization of the latex-containing plant resources. MethodStatistics on the meridians for properties and tastes， efficacy， medicinal parts， family and genus， and chemical components of TCM from latex-containing plants were carried out. A total of 53 TCM from latex-containing plants included in the 2020 edition of the Chinese Pharmacopoeia were screened by mining the Chinese Botanical Journal， Chinese Materia Medica， Dictionary of Traditional Chinese Medicines， and related literature. In addition， their meridians for properties and tastes， medicinal parts， chemical components， and TCM classifications were summarized and statistically analyzed by using Excel 2013 and ChiPlot 2023.3.31 software. ResultIt was found that latex-containing plants were mainly distributed in one kingdom， one phylum， two classes， and 20 families， and most of the TCM from latex-containing plants belonged to Dicotyledonaceae under Angiosperms. In terms of properties and tastes， plain>cold>warm>cool>hot and bitter>pungent>sweet>sour>salty. In terms of meridians， liver>lung>kidney>spleen=large intestine=stomach>heart>bladder=gallbladder=small intestines. In terms of medicinal parts， roots （root， rhizomes， tuberous root， and root bark）>resin>seed>whole herb （whole herb and above-ground part）>stem （stem and branch）>fruit>leaf>flower=skin. In terms of research on chemical components， they were mostly glycosides. In terms of TCM classification， they were mostly medicines for activating blood circulation and removing blood stasis. ConclusionThe TCM from latex-containing plants is mainly plain， with a uniform warm and cold distribution. The tastes are mainly bitter and pungent， and the major meridians are the liver and lung. The roots and resins are mainly used as medicines. The components mostly contain glycosides， alkaloids， and volatile oils， and most of them are medicines for activating blood circulation and removing blood stasis， as well as for removing heat and toxins. There is a certain degree of correlation among the growth habits， medicinal parts， chemical components， and the properties， tastes， and efficacy of the TCM from latex-containing plants. It may provide a reference for resource development and utilization of TCM from latex-containing plants.

ObjectiveThe relevant laws among the biological characteristics， medicinal parts， growth environment， and medicinal properties and efficacy of traditional Chinese medicines （TCM） from fungi were excavated， so as to strengthen the theory of distinguishing symptoms for quality and provide a reference for the development and utilization of TCM from fungi. MethodThe medicinal parts， meridians for properties and tastes， heterotrophic mode， and efficacy of commonly used TCM from fungi were summarized. By consulting the Compendium of Materia Medica， Shennong Materia Medica， Flora of China， and literature， the TCM from fungi indexed in the 2020 edition of the Chinese Pharmacopoeia and some local pharmacopeias were checked. ResultA total of 28 common TCM from fungi were selected. Different TCMs from fungi have different meridians for properties and tastes， medicinal parts， habits， and growth environments. The relevant information was counted. Among the four properties， plain>cold>warm. Among the five tastes， sweet>bitter>light>pungent=salty. In terms of medicinal parts， fruiting body>sclerotia>complex>spermia=outer skin=other. In terms of meridians， lung>liver=heart>spleen=kidney>stomach. In terms of habits， parasitism>saprophysis>symbiosis=facultative parasitism=facultative saprophysis. ConclusionTCM from fungi are mainly parasitic and saprophytic， and the plain property and sweet taste the most. The meridians are mostly lung， heart， and liver. Nourishment and diuresis are the main efficacy. There is a certain correlation between the color， habit， medicinal parts， and growth environment of TCM from fungi and their properties， tastes， and efficacy， providing comprehensive literature reference and theoretical basis for their in-depth research， clinical use， and resource development.

ObjectiveTo investigate the functions and characteristics of traditional Chinese medicine （TCM） from plant skin and their Chinese patent medicines and explore the related laws of the medicinal tissue， property， taste， efficacy， and clinical application， so as to strengthen the theory of identifying symptoms for qualities and provide references for the development and utilization of TCM from plant skin and their Chinese patent medicines. MethodBy reviewing the 2020 edition of the Chinese Pharmacopoeia and some local pharmacopeias， TCM from plant skin and their Chinese patent medicines were screened out， and the characteristics， functions， and precautions of TCM from plant skin and their Chinese patent medicines were summarized. Statistical analysis was carried out with Excel. ResultA total of 62 TCM from plant skin were found， mainly distributed in one kingdom， three phyla， and 31 families. In terms of the family genus， Rutaceae>Leguminosae>Cucurbitaceae. In terms of the medicinal tissue， bark>root bark>fruit bark>seed bark. In terms of property and taste， warm>cold>plain>cool>hot， and bitter>sweet=pungent>acidic. In terms of meridians， lung>liver>spleen>heart>colorectal>kidney>stomach=bladder. In terms of TCM classification， most of them belong to the category of heat-clearing medicines. There were 485 types of Chinese patent medicines from plant skin， with the most Chinese patent medicines containing Citri Reticulatae Pericarpium. Among the forms of administration， pills were the most predominant. In terms of the tastes of the medicines， bitter and sweet flavors predominated. In terms of functions， medicines for strengthening the body resistance were the most. For the precautions， contraindications during pregnancy were the most common. ConclusionThere is a correlation among medicinal tissue， property， taste， efficacy， and clinical application of TCM from plant skin. It is also necessary to pay attention to the contraindications of the medicines and rationally choose TCM from plant skin and their Chinese patent medicines under the guidance of TCM theory based on syndrome differentiation and treatment.

Objective To investigate the detection rate,epidemiology and resistance mechanism of methicil-lin-resistant Staphylococcus aureus(MRSA)in a hospital in recent 5 years.Methods A total of 762 strains of non repetitive Staphylococcus aureus detected from 2016 to 2020 in a hospital were collected retrospectively.Methicillin-sensitive Staphylococcus aureus(MSSA)was 392 strains(MSSA group)and 370 strains caused by MRSA(MRSA group),and 95 strains of MRSA isolated in 2020 were further used for resistance mechanism.Staphylococcus aureus was identified and tested for drug sensitivity by Vitek 2 automatic microbial system.Molecular epidemiological typing was determined by multilocus sequence typing.The biofilm formation was performed by crystal violet staining.PCR amplification was used to detect drug resistance genes,virulence genes and biofilm related genes,and logistic regression analysis was used to investigate the independent risk factors of its occurrence.Results The detection rate of MRSA in past five years was 48.56％,mainly was from pus samples and secretion samples(38.38％,33.51％respectively).MRSA was found in the general sur-gery(18.65％)and otorhinolaryngology(12.70％).ST88 was the most common multilocus sequence typing(37.89％),and followed by ST951(24.21％).Moderate biofilm formation was the most common,accounting for 74.73％.Multivariate regression analysis showed that compared with MSSA group,hypoproteinemia,en-docrine system diseases,wound infection and history of antibiotic use within six months were the independent risk factors for infection in MRSA group.Compared with the control group,hospital transfer,wound infection and tumor were independent risk factors for infection in MRSA group(P＜0.05).Conclusion The detection rate of MRSA in a hospital is high,and the carrying rate of various drug-resistant genes is high.The hospital should pay attention to the prevalence of MRSA and related risk factors,so as to prevent it early.

Fever of unknown origin(FUO)is a difficulty in clinical diagnosis and treatment.Patients with FUO come to seek medical consultation usually with fever as the main complaint,and the accompanying symptoms and signs are generally atypical.The pathogenesis of FUO remains conflicting in the field of modern western medicine,and its treatment is still focused on empirical anti-inflammatory management,which has the deficiency of delayed diagnosis,limited therapeutic options,poor therapeutic effects,and obvious adverse reactions.In the field of traditional Chinese medicine(TCM),FUO generally results from the dysfunction of zang-fu organs and the imbalance of yin and yang,and has the clinical features of long duration of illness,unknown etiology,complexity of illness,recurrent attacks,and difficult to be cured.Based on the six-meridian syndrome differentiation,Chief Physician LI Chuang-Peng pointed out that the pathogenesis of FUO is characterized by the combined disease of shaoyin and yangming,and put forward the therapeutic principle of warming shaoyin and unblocking yangming.He proposed the use of Dahuang Fuzi Decoction(mainly composed of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata)plus Yiyi Fuzi Baijiang Powder(mainly composed of Coicis Semen,Aconiti Lateralis Radix Praeparata and Patriniae Herba)to subside fever and eliminate pathogen,together with Asari Radix et Rhizoma for guiding the medicine directly to the shaoyin.Moreover,therapies of strengthening and activating spleen and stomach,nourishing yin to produce fluid,and unblocking the blood vessels can be used for eliminating the pathogen and supporting the healthy qi.

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.