The relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor (InsR) and insulin resistance (IR) in patients with gestational diabetes mellitus (GDM) was investigated. The InsR expression and TP in skeleton muscle tissue were determined by Western blotting and immunoprecipitation in women with GDM (GDM group, n=22), normal pregnant women (normal pregnancy group, n=22) and normal non-pregnant women (normal non-pregnant group, n=13). Fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by oxidase assay and immunoradioassay. The results showed that the levels of FPG (5.61±0.78 mmol/L), FINS (15.42±5.13 mU/L) and Homeostasis model assessment-IR (HOMA-IR) (1.21±0.52) in GDM group were significantly higher than those in normal pregnancy group (4.43±0.46 mmol/L, 10.56±3.07 mU/L and 0.80±0.31 respectively) (P<0.01). The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal non-pregnant group (7.56±2.31 mU/L and 0.47±0.26 respectively) (P<0.01). There was no significant difference in the InsR expression level among the three groups (P>0.05). TP of InsR with insulin stimulation was significantly decreased in GDM group (0.20±0.05) as compared with normal pregnancy group (0.26±0.06) (P<0.01). TP of InsR with insulin stimulation in normal pregnancy group was lower than that in normal non-pregnant group (0.31±0.06) (P<0.01). TP of InsR with insulin stimulation was negatively related with HOMA-IR in GDM group (r=-0.525, P<0.01). There was no correlation between the protein expression of InsR and HOMA-IR in GDM group (r=-0.236, P>0.05). It was suggested that there is no significant correlation between the protein expression of InsR in skeletal muscle and IR in GDM, but changes in TP of InsR are associated with IR in GDM.

OBJECTIVETo investigate the expression of tripartite-motif protein 25 (TRIM25) and pyruvate kinase M2 (PKM2) protein in non-small cell lung cancer (NSCLC) and explore their role in the occurrence and progression of NSCLC.

METHODSThe expressions of TRIM25 and PKM2 protein were detected in 60 NSCLC specimens and 20 adjacent normal lung tissue (>5 cm from the lesions) with immunofluorescence histochemical method and in 10 fresh specimens of NSCLC with Western blotting. The results were analyzed in relation with the clinicopathological features of the patients.

RESULTSThe positivity rates of TRIM25 expression was 45% in the 60 lung carcinoma specimens, significantly higher than that in the 20 normal lung tissues (10%, P=0.005). TRIM25 protein was expressed in 28.6% of lung adenocarcinoma tissues and in 59.4% of squamous carcinoma tissues (P=0.017). TRIM25 protein expression was positively correlated with the TNM stages and lymph node metastasis of NSCLC (P<0.05). The expressions of PKM2 protein in 60 cases of lung carcinoma was 73.3%,while in 20 cases of normal lung tissues the expressions was 30%(P=0.001). The positivity rates of PKM2 expression differed significantly between lung adenocarcinoma and squamous carcinoma (57.1% vs 87.5%, P=0.008). An inverse correlation was noted between TRIM25 and PKM2 expressions (P=0.026).

CONCLUSIONTRIM25 and PKM2 protein may participate in the occurrence and progression of NSCLC, and their expressions are inversely correlated.

Adenocarcinoma ; enzymology ; Carcinoma, Non-Small-Cell Lung ; enzymology ; Carcinoma, Squamous Cell ; enzymology ; Carrier Proteins ; metabolism ; Humans ; Lung ; pathology ; Lung Neoplasms ; enzymology ; Lymphatic Metastasis ; Membrane Proteins ; metabolism ; Thyroid Hormones ; metabolism ; Transcription Factors ; metabolism ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases ; metabolism

The theoretical basis, location, belonging of zang-fu, treatment function and indications, applying principle and manipulation of Umbilical Ring acupoints in Zhuang medicine are explained in this paper. According to Zhuang medicine, umbilicus is an epitome of the body and all the zang-fu and organs in the body have corresponding epitomes like a fetus in front-standing position. The umbilicus is not only a micro-diagnosis system, but also a window for illness treatment that could be divided into superficial, middle and deep layer to respectively communicate different zang-fu and organs. The umbilical inner ring and outer ring are collectively called Umbilical Ring acupoints, they could dredge paths, regulate the balance of qi and blood to regulate qi, expel poison, tonify deficiency and remove stasis to treat many types of diseases in the whole body.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Medicine, Chinese Traditional ; Umbilicus ; anatomy & histology

In order to decrease the potential side-effects of human basic fibroblast growth factor (hbFGF) caused by its broadspectrum mitogenic activity, a single residue of hbFGF, the residue serine 108, was replaced with neutral alanine residue to construct a mutant of hbFGF (mhbFGF) with reduced mitogenic activity. The mutant was overexpressed in Escherichia coli BL21(DE3) by IPTG induction. The expression level of mhbFGF was about 30% of the total cellular protein. The expressed mhbFGF was purified by ionic exchange and heparin affinity chromatography from the supernatant of bacteria lysate. Measured by MTT method, the effect of mhbFGF on Balb/c 3T3 cell proliferation was much lower than that of wild-type hbFGF. The purified recombinant mhbFGF was prepared and sufficient for the following pharmacological and safety studies.

The relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor (InsR) and insulin resistance (IR) in patients with gestational diabetes mellitus (GDM) was investigated. The InsR expression and TP in skeleton muscle tissue were determined by Western blotting and immunoprecipitation in women with GDM (GDM group, n=22), normal pregnant women (normal pregnancy group, n=22) and normal non-pregnant women (normal non-pregnant group, n=13). Fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by oxidase assay and immunoradioassay. The results showed that the levels of FPG (5.61±0.78 mmol/L), FINS (15.42±5.13 mU/L) and Homeostasis model assessment-IR (HOMA-IR) (1.21±0.52) in GDM group were significantly higher than those in normal pregnancy group (4.43±0.46 mmol/L, 10.56±3.07 mU/L and 0.80±0.31 respectively) (P<0.01). The levels of FINS and HOMA-IR in normal pregnancy group were significantly higher than those in normal non-pregnant group (7.56±2.31 mU/L and 0.47±0.26 respectively) (P<0.01). There was no significant difference in the InsR expression level among the three groups (P>0.05). TP of InsR with insulin stimulation was significantly decreased in GDM group (0.20±0.05) as compared with normal pregnancy group (0.26±0.06) (P<0.01). TP of InsR with insulin stimulation in normal pregnancy group was lower than that in normal non-pregnant group (0.31±0.06) (P<0.01). TP of InsR with insulin stimulation was negatively related with HOMA-IR in GDM group (r=-0.525, P<0.01). There was no correlation between the protein expression of InsR and HOMA-IR in GDM group (r=-0.236, P>0.05). It was suggested that there is no significant correlation between the protein expression of InsR in skeletal muscle and IR in GDM, but changes in TP of InsR are associated with IR in GDM.
Adult ; Blood Glucose ; metabolism ; Blotting, Western ; Diabetes, Gestational ; blood ; metabolism ; Fasting ; blood ; Female ; Humans ; Insulin ; blood ; Insulin Resistance ; Muscle, Skeletal ; metabolism ; Phosphorylation ; Pregnancy ; Radioimmunoassay ; Receptor, Insulin ; metabolism ; Tyrosine ; metabolism

BACKGROUNDHyperbaric oxygen (HBO) intervention is a main therapeutic method and the curative effect has been certified for spinal cord injury (SCI), but the mechanisms of the neuroprotective effect of HBO on SCI remain elusive. This study aimed to observe the change in expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) after SCI at different time points and to investigate the neuroprotective mechanism of HBO on SCI in rats.

METHODSA total of 160 adult Sprague-Dawley rats, weighing between 250 and 300 g, were randomly assigned to four experimental groups (n = 40 per group). SCI group: SCI was created with a special NYU impactor of Allen's by a 25 gramcentimeter impacting energy on T10 of the spinal cord. SCI+HBO group: HBO therapy after SCI model was established. Sham operation (SH) group: only laminectomy of T10 and no impact on the spinal cord was done. SH+HBO group: HBO therapy after sham operation. The hindlimb functional recovery was evaluated using Basso, Beattie, and Bresnahan (BBB) score and the expressions of HIF-1α and VEGF were observed with fluorescent quantitation PCR and Western blotting method of six rats picked randomly from each group at different time points of 1, 3, 7, and 14 days after operation.

RESULTSRats in the SCI group and SCI+HBO group were paralyzed completely after operation with BBB 0-1 score. Rats in the SH group and SH+HBO group could walk after sham operation with BBB 20-21 score. The BBB score of rats in the SCI+HBO group (4.67±1.97 and 10.83±2.23) was higher than that in the SCI group (1.83±0.75 and 6.67±2.16) at 7 and 14 days time points obviously (P < 0.05). The expressions of HIF-1a and VEGF in the SCI group and SCI+HBO group were higher than in the SH group and SH+HBO group at any time point obviously (P < 0.05), while the SCI+HBO group presented the least expression of HIF-1α mRNA and protein (3.82±0.41 and 0.59±0.06; 2.26±0.41 and 0.37±0.05; 1.58±0.26 and 0.29±0.05) than that in the SCI group (6.36±0.58 and 0.76±0.07; 3.55±0.47 and 0.51±0.07; 2.27±0.39 and 0.40±0.06) respectively at 3, 7, and 14 days time points (P < 0.05) with significant difference and more expression of VEGF mRNA and protein (5.83±0.77 and 0.72±0.06; 4.59±0.51 and 0.63±0.06) than that in the SCI group (3.06±0.30 and 0.48±0.07; 2.25±0.24 and 0.39±0.09) respectively at 7 and 14 days time points (P < 0.05) with significant difference.

CONCLUSIONSHBO could improve the hind limb functional recovery after SCI in rats. The elevation and duration of the expression of VEGF and the reduction of expression of HIF-1α by HBO intervention may be inversely related in the repair of damaged spinal cord and neuroprotective effect.

Animals ; Hyperbaric Oxygenation ; methods ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo explore the pathological changes of pulmonary fibrosis induced by SiO2 in rats and pigs.

METHODSThe silicosis models in rats and pigs were established by non-exposure method. The pathologic changes in lung tissues of rats and pigs were observed with HE staining under a light microscopy and under a transmission electron microscopy (TEM), the expression of cytokines was detected by immunohistochemistry.

RESULTS(1) The main pathologic changes of silicosis models in rats and pigs included: in 7 ∼ 15 days after treatment, silica dusts, dust cells, a lot of macrophages, lung epithelial cells, a few neutrophils, macrophage alveolar inflammation and nodules of stage I were found in alveolar space; in 30 ∼ 90 days after treatment, many nodules of stage I-III or IV with lymphocytes infiltration were observed in respiratory bronchioles, alveoli, interlobular septa, the subpleural and around blood vessels and bronchi. (2) The expression levels of CK protein, SP-A protein, CD68, b-FGF, TNF-α, IL-6, TGF-β1, NFKappa/P50, Kappa/P65 and VEGF reduced with exposure time, but still were higher than those of the control. (3) The shed alveolar type I cells, proliferation of alveolar type II cells or macrophages and activated cellular function induced by silica were observed under TEM.

CONCLUSIONThe development of pulmonary fibrosis in silicosis models corresponded with the process from macrophages alveolar inflammation to pulmonary fibrosis.

Animals ; Cytokines ; metabolism ; Disease Models, Animal ; Epithelial Cells ; metabolism ; Female ; Lung ; cytology ; pathology ; Macrophages, Alveolar ; metabolism ; Male ; Neutrophils ; metabolism ; Rats ; Rats, Sprague-Dawley ; Silicosis ; pathology ; Swine

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10(7)/kg on day 0) and (4.0-6.8) ×10(7)/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions: Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.
Chimerism ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy, Adoptive ; Multiple Myeloma ; T-Lymphocytes

Pudilan Xiaoyan Oral Liquid has effects in clearing away heat and detoxifying,and is used to treat pharynx and throat swelling caused by the syndrome of excessive heat and toxin accumulation. Its efficacy is to relieve swelling and pain( redness,swelling and hot pain). It is included in the Chinese Pharmacopoeia of 2015 Edition,and has been listed in provincial health insurance directories of Shaanxi,Jiangsu,Liaoning,Hunan,Tianjin,Xinjiang and Hebei. It has been recommended by health departments of Beijing,Chongqing and other provinces as a preferred drug for the prevention and treatment of H1 N1 and HFMD,and listed in the diagnosis and Treatment Guide of HFMD by the Ministry of Health,the Clinical Application Guide of Chinese Patent Medicine edited by the Lung Department Disease Branch of China Association of Chinese Medicine,and the Clinical Practice Guide of Single Administration/Combined Administration of Antibiotics in Treatment of Common Infectious Diseases by China Association of Chinese Medicine. To further improve the clinician's understanding of drugs and better guide the rational clinical application,we invited front-line clinical experts from respiratory department,infectious department and dermatology of traditional Chinese and Western medicine to develop and compile the expert consensus. The consensus fully considered the clinical evidence and the expert clinical experience to give recommendations for clinical problems with evidence support and consensus suggestions for clinical problems without evidence support by the nominal group method.This consensus is based on clinical research evidence and expert experience in a simple and clear format,which provides a preliminary reference for the clinical use of the drug.
China ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs