[Objective] To explore the therapeutic effects of intravenous immunoglobulin (IVIG) on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC). [Methods] C57BL/6 mice were randomly assigned to the control group, the DSS group (model) and the DSS+IVIG group (treatment). The DSS group and the DSS+IVIG group received 3% DSS in drinking water to establish the acute UC mouse model. During the experiment, the DSS+IVIG group received IVIG (1 g/kg/2d) via tail vein injection, while the DSS group received equivalent saline via tail vein injection at the same dose and frequency. The symptoms of the mice were observed, body weight changes were recorded, and the disease activity index (DAI) was calculated daily. At the end of the experiment, hematoxylin-eosin (HE) staining was used to observe the pathological changes and inflammatory cell infiltration of colon tissue; Periodic acid-Schiff (PAS) staining was used to quantify the number of goblet cells; Luminex was used to detect the levels of inflammatory-related cytokines (such as TNF-α, IL-6 and MMPs) in colon; western blot and qRT-PCR were respectively used to detect the protein expression and mRNA levels of tight junction proteins (ZO-1, Occludin, Claudin-3). [Results] DSS induced weight loss, diarrhea, bloody stool, increased DAI score, and shortened colon length in mice. Compared with DSS group, after the administration of IVIG, the DAI score was significantly reduced (P<0.001), colon length was increased (P<0.001), infiltration of inflammatory cells and pathological damage were alleviated in colonic mucosa (P<0.001), the number of goblet cells were increased (P<0.05), and the levels of inflammatory-related cytokines TNF-α, IL-6, IL-6R, MMP2, MMP3 and Chitinase3like1 were decreased (all P<0.05). Western blot and qRT - PCR results showed that IVIG significantly up-regulated the protein expression of ZO-1, Occludin and claudin-3 (all P<0.05) and the mRNA levels of ZO-1 and Occludin (all P<0.05). [Conclusion] IVIG has protective effects on colitis by inhibiting the pathological release of inflammatory-related cytokines such as TNF-α, IL-6 and MMPs and restoring the integrity of intestinal barrier.

OBJECTIVES: To investigate the protective effect of catalpol against triptolide-induced liver injury and explore its mechanism to test the Fuzheng Zhidu theory for detoxification. METHODS: C57BL/6J mice were randomized into blank control group, catalpol group, triptolide group and triptolide+catalpol group. After 13 days of treatment with the agents by gavage, the mice were examined for liver tissue pathology, liver function, hepatocyte subcellular structure, lipid peroxidation, ferrous ion deposition and expressions of ferroptosis-related proteins in the liver. In a liver cell line HL7702, the effect of catalpol or the ferroptosis inhibitor Fer-1 on triptolide-induced cytotoxicity was tested by examining cell functions, Fe²⁺ concentration, lipid peroxidation, ROS level and the ferroptosis-related proteins. RESULTS: In C57BL/6J mice, catalpol significantly alleviated triptolide-induced hepatic injury, lowered the levels of ALT, AST and LDH, and reversed the elevation of Fe²⁺ concentration and MDA level and the reduction of GP_X level. In HL7702 cells, inhibition of ferroptosis by Fer-1 significantly reversed triptolide-induced elevation of ALT, AST and LDH levels. Western blotting and qRT-PCR demonstrated that catalpol reversed abnormalities in expressions of SLC7A11, FTH1 and GPX4 at both the mRNA and protein levels in triptolide-treated HL7702 cells. CONCLUSIONS The combined use of catalpol can reduce the hepatotoxicity of triptolide in mice by inhibiting excessive hepatocyte ferroptosis through the SLC7A11/GPX4 pathway.
Animals ; Phenanthrenes/toxicity* ; Ferroptosis/drug effects* ; Diterpenes/toxicity* ; Epoxy Compounds/toxicity* ; Mice, Inbred C57BL ; Hepatocytes/metabolism* ; Mice ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Iridoid Glucosides/pharmacology* ; Liver/metabolism* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Male ; Amino Acid Transport System y+/metabolism*

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Nonalcoholic fatty liver disease （NAFLD） is one of the most common complications of type 2 diabetes mellitus （T2DM）. Cell death caused by iron-lipid disorder is a new mode of regulating programmed cell death， which is characterized by lipid peroxidation induced by the accumulation of lipid reactive oxygen species and excessive accumulation of iron ions induced by iron metabolism disorders. Among them， iron homeostasis disorder and metabolic pathway disorder are the main causes of iron-lipid disorder， which play an important role in a variety of pathological processes related to cell death. Because the liver is an important organ for iron storage and lipid metabolism， iron-lipid disorder is an ideal target for liver disease， and inhibition of iron-lipid disorder may become a new strategy for the treatment of NAFLD. However， the pathogenic relationship and mechanism between NAFLD and iron-lipid disorder have not been fully elucidated. Based on the complex molecular regulation mechanism of iron-lipid disorder， by expounding the role of iron-lipid disorder in NAFLD and its related mechanism， this paper summarizes the research status of traditional Chinese medicine on the target treatment of NAFLD in recent years， so as to provide a new perspective and point out a new direction for the treatment of NAFLD in the future.

OBJECTIVE To explore the characteristics and regulations of adverse drug reactions （ADR） caused by apatinib， and to provide a reference for the safe use of apatinib in clinic. METHODS Case and group reports on ADR and safety evaluation of apatinib were retrieved from Chinese and English databases such as CNKI， Wanfang medical network， VIP and PubMed since its listing in 2014， literature data were extracted and statistically analyzed after screening. RESULTS Totally 101 cases were included， involving 221 ADR. In the above cases， the male-to-female ratio was 1.24∶1， with the highest proportion of patients aged 51 to 70 years， most of the patients were given a dose of 500 mg or more， and the patients given low dose of apatinib combined with other antitumor drugs were also likely to have ADR. One to two types of adverse reaction were the most common， while the types could reach up to six. Most ADR occurred within 30 days after medication， and the systems/organs involved were mainly the cardiovascular system damage，skin and its accessories damage， gastrointestinal system damage and urinary system damage； the main clinical manifestations were hypertension/aggravation，hand-foot syndrome，abdominal pain diarrhea and albuminuria， etc. Hypertension/aggravation， hand-foot syndrome and myelosuppression were the most common serious ADR. Most ADR could be improved/cured by suspension of administration， dose downregulation and symptomatic treatment. All 4 patients who died had underlying diseases， and their ECOG scores all ≥2 points. Special ADR （such as reversible posterior encephalopathy syndrome， psychiatric disorders， and cognitive impairment） were mostly caused by apatinib itself， or may be caused by apatinib in combination with the primary or underlying disease. CONCLUSIONS Advanced age， large dose， combination medication， underlying diseases and poor physical condition might be the high risks for ADR caused by apatinib. It is recommended to monitor the blood pressure，urine protein and skin of hands and feet of all patients with medication on a daily basis，pay attention to the occurrence of special ADR， and timely detect abnormal states and give effective intervention，so as to avoid the aggravation of ADR and other secondary ADR.

Objective:To describe and analyze suicide risk of patients with schizophrenia,major depressive disorder,and bipolar disorder.Methods:A total of 2 016 patients with schizophrenia,903 patients with major de-pressive disorder,and 381 patients with bipolar disorder from inpatients,clinics,or communities who met the diag-nostic criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition were recruited.All patients were interviewed by psychiatrists using the Mini International Neuropsychiatric Interview to diagnose mental disor-ders and assess suicide risk,as well as Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)to as-sess symptoms.Differences and risk factors of suicide risk among three types of mental disorders were explored u-sing multivariate logistic regression analysis.Results:In the past one month,37 patients with schizophrenia(1.8％),516 patients with major depressive disorder(57.1％),and 102 patients with bipolar disorder(26.8％)had suicide risk.Compared with patients with schizophrenia,suicide risk in patients with major depressive disorder(OR=36.50)and bipolar disorder(OR=20.10)increased.Female(OR=1.87),smoking(OR=1.76),family history of suicide(OR=5.09),higher score of CRDPSS hallucination(OR=1.80),and higher score of CRDPSS depression(OR=1.54)were risk factors of suicide risk of patients.Conclusions:Suicide risk of patients with ma-jor depressive disorder and bipolar disorder is higher than that of patients with schizophrenia.In clinical practice,it is important to regularly assess suicide risk of patients.Patients who experience symptoms of hallucination and de-pression should be paid more attention to.

Objective:To explore the clinical characteristics and related socio-demographic factors of schizo-phrenia patients with different ages of onset.Methods:Totally 2 016 patients with schizophrenia aged 15 to 70 were selected according to the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.All of the patients were interviewed by psychiatrists using the Mini International Neuropsy-chiatric Interview to diagnose schizophrenia,Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)and the Positive and Negative Syndrome Scale(PANSS)to assess symptoms.The cut-off points were 18 and 25 years old for three age groups,i.e.early onset(EOS),youth onset(YOS)and adult onset(AOS).Statistical analy-ses were performed by analysis of variance Pearson correlation analysis,and multivariate linear regression.Results:The early-onset patients had the highest total PANSS score(73.8±28.0)and CRDPSS score(11.7±5.4).Fe-male gender,high education level,Han ethnicity,early onset age,and slower onset of illness were negatively corre-lated with the total and dimension score of PANSS scale and CRDPSS scale(standardized regression coefficient:0.04-0.47),and income level and smoking were negatively correlated with those score(standardized regression coefficient:-0.04--0.14).Conclusion:Early-onset schizophrenia patients have more severe symptoms,and fe-male,high education level,early-onset disease,and chronic onset are the risk factors of symptom severity in patients with schizophrenia.

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.

BACKGROUND:The osteogenic differentiation of mesenchymal stem cells is regulated by a variety of molecules.Long non-coding RNA(lncRNA)has attracted much attention because they can participate in regulating a variety of biological processes,but the regulatory role of lncRNA on osteogenic differentiation of mesenchymal stem cells has not been fully explored. OBJECTIVE:To explore the effect of lncRNA Gm16104 on osteogenic differentiation of C3H10T1/2 mesenchymal stem cells. METHODS:The C3H10T1/2 mesenchymal stem cells were induced into osteogenic differentiation by bone morphogenetic protein-2.Alkaline phosphatase staining was performed to identify the osteogenic differentiation of the cells 5 days after osteogenic induction.Expression levels of alkaline phosphatase and lncRNA Gm16104 were detected by qRT-PCR after 0,1,3,and 5 days of osteogenic differentiation.After transfection of the overexpression plasmid of pcDNA-Gm16104,the osteogenic differentiation was identified by alkaline phosphatase staining and qRT-PCR 4 days after osteogenic induction.The expression levels of osteogenesis-related signalling pathway proteins were detected by western blot assay. RESULTS AND CONCLUSION:(1)After 5 days of osteogenic induction,alkaline phosphatase activity was significantly increased.(2)Compared with 0 days,expression levels of the osteogenic marker gene alkaline phosphatase increased and expression levels of Gm16104 decreased after 1,3,and 5 days of osteogenic induction.(3)Transfection of C3H10T1/2 cells with pcDNA-Gm16104 plasmid significantly increased the expression level of Gm16104.(4)Overexpression of Gm16104 inhibited alkaline phosphatase activity,the expression levels of the osteogenic marker gene alkaline phosphatase and the osteogenesis-related transcription factor Osterix.(5)Overexpression of Gm16104 inhibited phosphorylated protein expression of PI3K and Akt.(6)The above results suggest that overexpression of Gm16104 may inhibit osteogenic differentiation of C3H10T1/2 mesenchymal stem cells through the PI3K/Akt signaling pathway.

Objective To study the clinical effect of levosimendan combined with recombinant human brain natriuretic peptide(rhBNP)on patients with acute heart failure.Methods A total of 100 patients with acute heart failure in the hospital from December 2019 to December 2021 were selected as the research sub-jects.According to different treatment options,the subjects were divided into the control group,levosimendan group,rhBNP group and combined treatment group,with 25 cases in each group.The control group received traditional conventional diuretic,tube expansion and other treatment;the levosimendan group was treated with levosimendan on the basis of the control group;the rhBNP group was treated with rhBNP on the basis of the control group;the combined treatment group was treated with levosimendan and rhBNP on the basis of the control group.The improvement of New York Heart Association(NYHA)classification,death,rehospitaliza-tion rate,6-minute walking distance,improvement of serological indicators and adverse reactions were recor-ded in each group.Results Before treatment,there was no significant difference in baseline data between the groups(P>0.05).On the 1 st and 3 rd day after treatment,the improvement of NYHA classification in the combined treatment group was better than that in the other groups(P<0.05),and the improvement of NY-HA classification in the levosimendan group and rhBNP group was better than that in the control group(P<0.05).The readmission rate within 6 months after treatment in the combined treatment group was lower than that in the other groups(P<0.05).At 5 and 9 days after treatment,the 6-minute walking distance in the combined treatment group was longer than that in the other groups(P<0.05).At 9 days after treatment,the left ventricular ejection fraction(LVEF)in the combined treatment group was higher than that in the other groups(P<0.05),and the level of N-terminal B-type natriuretic peptide(NT-proBNP)in the combined treatment group was lower than that in the other groups(P<0.05).No significant difference was found in the comparison of the occurrence of adverse reactions among the four groups(P>0.05).Conclusion The combina-tion of levosimendan and rhBNP in the treatment of patients with acute heart failure is superior to traditional treatment and monotherapy in early clinical improvement,and dose not increase the incidence of adverse reactions.