LIU Ruifen's Experience in Treating Endometrial Hyperplasia with Three-staged Stasis Dispelling Method / 中医杂志

This paper summarized professor LIU Ruifen's clinical experience in treating endometrial hyperplasia. It is believed that the core pathogenesis of endometrial hyperplasia is internal obstruction of uterus and intrauterine collaterals by latent stasis. Based on the clinical manifestations， the menstrual cycle is divided into three stages， that is menstrual period， menstrual leakage period， and clear menstrual period， and the method of “three-staged stasis dispelling” is proposed. During the menstrual period， it is appropriate to move qi and invigorate blood， dissolve stasis and disperse concretions， with self-made Gongqing Formula （宫清方）. For menstrual leakage period， it is suggested to boost qi and clear heat， dispel stasis and stanch bleeding， with self-made Tongyong Zhixue Formula （通用止血方）. In terms of clear menstrual period， the method of dissolving phlegm and dissipating masses， moving qi and dispelling stasis is advised， and self-made Zhitong Tiaoxue Formula （止痛调血方） can be used. Simultaneously， attention should be paid to the combination of syndrome differentiation and disease differentiation， as well as collaborative diagnosis and treatment with traditional Chinese and Western medicine.

Quality control mechanism of mitochondria by 3,4-dihydroxybenzaldehyde through OGT-PINK1 pathway / 中国中药杂志

Based on the O-GlcNAc transferase(OGT)-PTEN-induced putative kinase 1(PINK1) pathway, the mechanism of 3,4-dihydroxybenzaldehyde(DBD) on mitochondrial quality control was investigated. Middle cerebral artery occlusion/reperfusion(MCAO/R) rats were established. SD rats were randomized into sham operation group(sham), model group(MCAO/R), DBD-L group(5 mg·kg~(-1)), and DBD-H group(10 mg·kg~(-1)). After 7 days of administration(ig), MCAO/R was induced in rats except the sham group with the suture method. Twenty-four h after reperfusion, the neurological function and the percentage of cerebral infarct area were measured. Based on hematoxylin and eosin(HE) staining and Nissl staining, the pathological damage of cerebral neurons was examined. Then the ultrastructure of mitochondria was observed under the electron microscope, and the co-localization of light chain-3(LC3), sequestosome-1(SQSTM1/P62), and Beclin1 was further detected by immunofluorescence staining. It has been reported that the quality of mitochondria can be ensured by inducing mitochondrial autophagy through the OGT-PINK1 pathway. Therefore, Western blot was employed to detect the expression of OGT, mitophagy-related proteins PINK1 and E3 ubiquitin ligase(Parkin), and mitochondrial kinetic proteins dynamin-like protein 1(Drp1) and optic atrophy 1(Opa1). The results showed that MCAO/R group had neurological dysfunction, large cerebral infarct area(P<0.01), damaged morphological structure of neurons, decreased number of Nissl bodies, mitochondrial swelling, disappearance of mitochondrial cristae, decrease of cells with LC3 and Beclin1, rise of cells with P62(P<0.01), inhibited expression of OGT, PINK1, and Parkin, up-regulated expression of Drp1, and down-regulated expression of Opa1 compared with the sham group(P<0.01). However, DBD improved the behavioral deficits and mitochondrial health of MCAO/R rats, as manifested by the improved morphology and structure of neurons and mitochondria and the increased Nissl bodies. Moreover, DBD increased cells with LC3 and Beclin1 and decreased cells with P62(P<0.01). In addition, DBD promoted the expression of OGT, PINK1, Parkin, and Opa1 and inhibited the expression of Drp1, enhancing mitophagy(P<0.05, P<0.01). In conclusion, DBD can trigger PINK1/Parkin-mediated brain mitophagy through the OGT-PINK1 pathway, which plays a positive role in maintaining the health of the mitochondrial network. This may be a mitochondrial therapeutic mechanism to promote nerve cell survival and improve cerebral ischemia/reperfusion injury.

Discussion on the pathogenesis and therapeuticthoughts in traditional Chinese medicine of flat foot,based on the theory of"spleen-kidney-muscle-bone" / 现代医院

By combing and summarizing the interpretation of"spleen-kidney-muscle-bone"related theories in tra-ditional Chinese medicine classics and combining with clinical practice,this paper innovatively puts forward the pathogenesis and treatment ideas of congenital flat foot in traditional Chinese medicine,in order to provide theoretical basis and beneficial reference for the holistic treatment of flat foot in traditional Chinese medicine.

The role of intravoxel incoherent motion diffusion-weighted imaging in distinguishing diabetic nephropathy from non-diabetic renal disease in diabetic patients / 中华内科杂志

Objective:To investigate the intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in the differential diagnosis of diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) among patients with type 2 diabetes mellitus (T2DM).Methods:A diagnostic test. In this prospective study, patients with T2DM who underwent both IVIM-DWI and renal biopsy at the First Medical Center of Chinese PLA General Hospital between October 2017 and September 2021 were consecutively enrolled. IVIM-DWI parameters including perfusion fraction (f), pure diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were measured in the renal cortex, medulla, and parenchyma. Patients were divided into the DN group and NDRD group based on the renal biopsy results. IVIM-DWI parameters, clinical information, and diabetes-related biochemical indicators between the two groups were compared using Student′s t-test or Mann-Whitney U test. The correlation of IVIM-DWI parameters with diabetic nephropathy histological scores were analyzed using Spearman′s correlation analyzes. The diagnostic efficiency of IVIM-DWI parameters for distinguishing between DN and NDRD were assessed using the receiver operating characteristic (ROC) curves. Results:A total of 27 DN patients and 23 NDRD patients were included in this study. The DN group comprised 19 male and 8 female patients, with an average age of 52±9 years. The NDRD group comprised 16 male and 7 female patients, with an average age of 49±10 years. The DN group had a higher D* value in the renal cortex and a lower f value in the renal medulla than the NDRD group (9.84×10 -3 mm 2/s vs. 7.35×10 -3 mm 2/s, Z=-3.65; 41.01% vs. 46.74%, Z=-2.29; all P<0.05). The renal medulla D* value was negatively correlated with DN grades, interstitial lesion score, and interstitial fibrosis and tubular atrophy (IFTA) score ( r=-0.571, -0.409, -0.409; all P<0.05) while the renal cortex f value was positively correlated with vascular sclerosis score ( r=0.413, P=0.032). The renal cortex D* value had the highest area under the curve (AUC) for discriminating between the DN and NDRD groups (AUC=0.802, sensitivity 91.3%, specificity 55.6%). Conclusion:IVIM-derived renal cortex D* value can be used non-invasively to differentiate DN from NDRD in patients with T2DM that can potentially facilitate individualized treatment planning for diabetic patients.

Clinical significance of loss of chromosome Y in patients with multiple myeloma / 中华检验医学杂志

Objective:To explore the risk stratification and prognostic significance of loss of chromosome Y (LOY) in patients with multiple myeloma (MM).Methods:The clinical data of 193 male patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from January 2018 to January 2020 were analyzed retrospectively and divided into a normal karyotype group(178) and a LOY karyotype group (15) according to the results of their primary conventional cytogenetics. Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis, between the two groups. The clinical prognostic significance of LOY was summarized through survival analysis and Cox regression. Results:Among the newly diagnosed male MM patients, 8%(15/178) were confirmed with LOY cases. The proportion of patients with Revised International Staging System(R-ISS) stage Ⅲ was significantly higher in the LOY group (8/15) than that in the normal karyotype group (40/178)(χ 2=7.052, P<0.01). A higher proportion of 1q21 amplification also occurred in the LOY group (10/13 vs 77/162)(χ 2=4.159, P<0.05). The proportion of complete response(CR)/stringent complete response(sCR) in the normal karyotype group after the fourth chemotherapy (63/171) was significantly higher than that in the LOY group (1/15)(χ 2=5.564, P<0.05). The proportion of progressive disease (PD) was lower in the normal karyotype group (16/171 vs 4/15) (χ 2=4.306, P<0.05). The 2-year progression-free survival (PFS) of MM patients for the LOY group was significantly shorter compared to that for the normal karyotype group ( Z=?3.201, P<0.01). Univariate survival analysis showed that PFS was significantly shorter in newly diagnosed MM patients with Creatinine(Cr)≥93 μmol/L, β 2-microglobulin (β 2-MG)≥4.0 mg/L, serum free light chain(sFLC)<0.06, bone marrow plasma cells (BMPC)≥30%, R-ISS stage Ⅲ, failure to achieve CR/sCR after the fourth chemotherapy, with LOY, 1q21 amplification, P53 deletion and t(4;14) ( P<0.05). Cox regression analysis showed that Cr≥93 μmol/L( HR=4.460, 95% CI 1.615-12.314, P=0.004), sFLC<0.06( HR=2.873, 95% CI 1.206-6.849, P=0.017), failure to achieve CR/sCR after the fourth chemotherapy( HR=3.522, 95% CI 1.437-8.634, P=0.006)and with LOY( HR=3.485, 95% CI 1.473-8.249, P=0.006)were independent risk factors for PFS in newly diagnosed MM patients. Conclusions:LOY is an independent risk factor for poor prognosis. It is important for the clinical outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Influencing Factors of Horizontal Movement Distance of Bodies in High Falling Deaths / 法医学杂志

OBJECTIVES@#To explore the influencing factors of the horizontal distance of bodies in the high falling scene and the feasibility of inferring the falling mode based on it.@*METHODS@#A total of 614 high falling deaths and 15 cases of corpse dumping from high altitudes were collected. The relationship between the horizontal distance and the falling height, as well as the sex, age and manner of death (suicide, accident and corpse dumping) were observed.@*RESULTS@#The horizontal distance increased with the increase of falling height, and the difference among the height groups was statistically significant. The horizontal distance decreased with the increase of the age of the deceased, in each height group, the difference between the group over 60 years old and other age groups was statistically significant (P<0.05). The horizontal distance of male deceased was (1.99±0.27) m, which was greater than that of female deceased (1.88±0.19) m, and the difference was statistically significant in partial height groups (P<0.05). Roof falls had a greater horizontal movement distance than window falls. Except for the >20-30 m group, there was no significant difference in horizontal distance between suicide high falls and accidental high falls in other height groups.@*CONCLUSIONS@#The horizontal distance is affected by the falling height, the sex and age of the victim, and the spatial characteristics of the falling starting point.

Clinical efficacy of short-term deep sedation after decompressive craniectomy with hematoma removal in patients with hypertensive intracerebral hemorrhage / 中国基层医药

Objective:To investigate the efficacy and safety of short-term deep sedation after conventional decompressive craniotomy with hematoma removal in patients with hypertensive intracerebral hemorrhage.Methods:Sixty patients with hypertensive intracerebral hemorrhage who underwent conventional decompressive craniotomy with hematoma removal in the People′s Hospital of Yueqing, China between March 2018 and May 2019 were included in this study. They were randomly divided into deep sedation and light sedation groups ( n = 30/group). The deep sedation group was administered propofol (0.6-1.2 mg/kg/h) combined with sedate fentanyl to achieve the level of sedation to Richmond Agitation-Sedation Scale (RASS) -3 to -4 points and to the level of pain to Critical Care Pain Observation Tool (CPOT) 0-1 point. The duration of sedation and analgesia was for 48 hours. The light sedation group was administered propofol (0.2-0.5 mg/kg/h) combined with sedate fentanyl to achieve the level of sedation to RASS -1 to -2 points and to the level of pain to CPOT 0-1 point. The duration of sedation and analgesia was rehemorrhage for 48 hours. Patients in the two groups were intravenously administered Urapidil to control blood pressure to be 120-160/60-90 mmHg. In addition, all patients were subjected to mechanical ventilation, dehydration, reduction of intracranial pressure, anti-infection and symptomatic treatment. At 0, 6, 12, 24 and 48 hours after surgery, heart rate, mean arterial pressure, intracranial pressure, recurrence of hemorrhage, ventilator-associated pneumonia, lower extremity deep venous thrombosis, and gastrointestinal bleeding were monitored. Results:At 6, 12, 24 and 48 hours after surgery, the heart rate, mean arterial pressure, and intracranial pressure in the deep sedation group were significantly lower than those in the light sedation group ( P < 0.05 or P < 0.01). The recurrence of rehemorrhage and the incidence of gastrointestinal bleeding in the deep sedation group were 3.33% (1/30) and 6.67% (2/30), respectively, which were significantly lower than those in the light sedation group [10.00% (3/30), 20.00% (6/30), χ2 = 1.071, 2.307, both P < 0.05). There were no significant incidences in ventilator-associated pneumonia [30.00% (9/30) vs. 23.30% (7/30), χ2 = 0.340, P > 0.05] and lower extremity deep venous thrombosis [10.00% (3/30) vs. 6.67% (2/30), χ2 = 0.340, P > 0.05]. Conclusion:Short-term deep sedation after conventional decompressive craniotomy with hematoma removal can lower the heart beat, mean arterial pressure, intracranial pressure, the postoperative recurrence of hemorrhage, and the incidence of gastrointestinal bleeding in patients with hypertensive cerebral hemorrhage.

In vitro antibacterial effects of imipenem combined with conventional antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae / 中国基层医药

Objective:To investigate the in vitro antibacterial effects of imipenem combined with common antibiotics on bla KPC-2 type carbapenem resistant klebsiella pneumoniae (CRKP) targeting bla KPC-2 gene. Methods:Six strains of unrepeated bla KPC-2 type confirmed by polymerase chain reaction and DNA sequence were isolated in Yueqing People's Hospital, China between January 2018 and January 2019 were included in this study. The susceptibility rate of imipenem against nine conventionally used antibiotics was determined. The sensitivity test of imipenem combined with eight antibiotics was performed with the checkerboard method. Fractional inhibitory concentration was calculated to assess the efficacy of imipenem combined with common antibiotics. The in vitro treatment time-antibacterial effect curve was drawn to evaluate the antibacterial effects. Results:The resistance rate of six strains of bla KPC-2 type was 100.00% (6/6) for imipenem, meropenem, ceftazidime, ciprofloxacin, rifampicin and cefotaxime, and it was 66.67% (4/6) for minocycline and clavulanic acid and 33.33% (2/6) for tigecycline. Imipenem combined with tigecycline had a better antibacterial effect and exhibited a synergistic effect on four strains of bla KPC-2 type CRKP and an additive effect on two strains of Bla KPC-2 type CRKP. The curve of time for in vitro treatment of KPN2 with imipenem combined with tigecycline against bactericidal effect revealed that the antibacterial rate of imipenem at the 1/2 minimum inhibitory concentration combined with tigecycline at the 1/4 minimum inhibitory concentration was > 95% at (t+2) and the antibacterial effect could maintain (t+10) hours to (t+12) hours. The antibacterial rate of imipenem combined with tigecycline against strain 002 was gradually decreased with time, and the growth curve of strain 002 rised gradually. Conclusion:In vitro drug sensitivity test revealed that imipenem combined with tigecycline exhibits a good synergistic effect on bla KPC-2 type CRKP. Findings from this study provide a reference for clinical treatment of bla KPC-2 type CRKP.

Crystal structure of SARS-CoV-2 papain-like protease

The pandemic of coronavirus disease 2019 (COVID-19) is changing the world like never before. This crisis is unlikely contained in the absence of effective therapeutics or vaccine. The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays essential roles in virus replication and immune evasion, presenting a charming drug target. Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology, inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development. In this study, we sought to provide structural frameworks for PLpro inhibitor design. We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111S, which shares many structural features of SARS-CoV PLpro. This crystal form has unique packing, high solvent content and reasonable resolution 2.5 Å, hence provides a good possibility for fragment-based screening using crystallographic approach. We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture. We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARS-CoV-2 with the IC

Recent advances in emerging three-dimensional in vitro models for sport-related traumatic brain injury / 生物医学工程学杂志

Sports-related traumatic brain injury (srTBI) is a traumatic brain injury (TBI) caused by sports, which can result in cognitive and motor dysfunction. Currently, research on the molecular mechanism of srTBI and related drug development mainly relies on monolayer culture models and animal models. However, many differences exist in cell populations and inflammatory responses between these models and human pathophysiological processes. Most of the researches derived from the models can't effectively conducted translational research. Emerging three-dimensional (3D)

Effect of (, TLZT) gel preparation on p53 /miR-502-5p /NF-κBp65 in synovial tissue of knee osteoarthritis / 中国骨伤

OBJECTIVE@#To observe effects of (, TLZT) gel preparation on p53, miR-502-5p, NF-κBp65 in synovial tissue of knee osteoarthritis (KOA), and to explore mechanism of TLZT gel preparation in treating KOA.@*METHODS@#Thirthy-six Wistar rats aged 8 weeks and weighed 200 to 220 g (meaned 208 g) were randomly divided into normal group, model group and traditional Chinese medicine (TCM) group, 12 rats in each group. KOA model was established by modified Hulth method. After 4 weeks of modeling, TCM group treated with TLZT gel preparation for external use, 3 times daily for 2 weeks;normal group and model group were fed normally without intervention. After treatment, morphological changes of specimens in each group were observed, changes of miR-502-5p in synovial tissue were detected by qPCR, and contents of p53, NF-κBp65, IL-1β, TNF-α, MMP-13 in synovial tissue were detected by qPCR and Western Blot respectively.@*RESULTS@#(1)Morphological observation of specimens showed that the articular cartilage in model group was hyaline and uneven, the synovial membranes were hypertrophic and proliferative with a large number of inflammatory cells infiltrating, the joint fluid was thicker in texture;the articular cartilage in TCM group was more transparent and smooth, synovial hyperplasia was mild with a small amount of inflammatory cell infiltration, the texture of articular fluid was clear and sparse. (2) Compared with normal group, content of miR-502-5p of synovial tissue in model and TCM group were increased, mRNA and expression of p53 decreased, expression of NF-κBp65, IL-1β, TNF-α, MMP-13 increased. (3)Compared with model group, content of miR-502-5p in synovial tissue of TCM group decreased (<0.05), mRNA and protein expression of p53 increased (<0.05), mRNA and protein expression of NF-κBp65, IL-1β, TNF-α, MMP-13 decreased (<0.05).@*CONCLUSION@#Expression of p53, miR-502 -5p, NF -κBp65 in synovial tissue is closely related to synovial hyperplasia and inflammatory reaction, TLZT gel preparation may reduce proliferation and inflammatory reaction of KOA synovium by regulating the expression of p53, miR- 502-5p, NF-κBp65 in synovial tissues.

Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice / 中华医学杂志(英文版)

OBJECTIVE@#Cryoglobulinemia often causes systemic vasculitis, thereby damaging to skin and internal organs including kidneys, even life-threatening. This review aimed to introduce the advances in understanding, detection, and treatment of this disease in recent years, with a particular concern to clinical practice.@*DATA SOURCES@#All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019.@*STUDY SELECTION@#This review selected important original articles, meaningful reviews, and some reports on cryoglobulinemia published in recent years and in history, as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia.@*RESULTS@#Diagnosis of cryoglobulinemia relies on serum cryoglobulin test, in which to ensure that the blood sample temperature is not less than 37°C in the entire pre-analysis phase is the key to avoid false negative results. Cryoglobulinemic vasculitis (Cryo Vas), including cryoglobulinemic glomerulonephritis (Cryo GN), usually occurs in types II and III mixed cryoglobulinemia, and can also be seen in type I cryoglobulinemia caused by monoclonal IgG3 or IgG1. Skin purpura, positive serum rheumatoid factor, and decreased serum levels of C4 and C3 are important clues for prompting types II and III Cryo Vas. Renal biopsy is an important means for diagnosis of Cryo GN, while membranous proliferative GN is the most common pathological type of Cryo GN. In recent years, great advances have been made in the treatment of Cryo Vas and its underlying diseases, and this review has briefly introduced these advances.@*CONCLUSIONS@#Laboratory examinations of serum cryoglobulins urgently need standardization. The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.

Regulatory factor X5 promotes hepatocellular carcinoma progression by transactivating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta and suppressing apoptosis / 中华医学杂志(英文版)

BACKGROUND@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*METHODS@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*RESULTS@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*CONCLUSION@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

Regulatory factor X5 promotes hepatocellular carcinoma progression by transactivating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta and suppressing apoptosis / 中华医学杂志(英文版)

Background@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*Methods@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*Results@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*Conclusion@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice / 中华医学杂志(英文版)

Objective@#Cryoglobulinemia often causes systemic vasculitis, thereby damaging to skin and internal organs including kidneys, even life-threatening. This review aimed to introduce the advances in understanding, detection, and treatment of this disease in recent years, with a particular concern to clinical practice.@*Data sources@#All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019.@*Study selection@#This review selected important original articles, meaningful reviews, and some reports on cryoglobulinemia published in recent years and in history, as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia.@*Results@#Diagnosis of cryoglobulinemia relies on serum cryoglobulin test, in which to ensure that the blood sample temperature is not less than 37°C in the entire pre-analysis phase is the key to avoid false negative results. Cryoglobulinemic vasculitis (Cryo Vas), including cryoglobulinemic glomerulonephritis (Cryo GN), usually occurs in types II and III mixed cryoglobulinemia, and can also be seen in type I cryoglobulinemia caused by monoclonal IgG3 or IgG1. Skin purpura, positive serum rheumatoid factor, and decreased serum levels of C4 and C3 are important clues for prompting types II and III Cryo Vas. Renal biopsy is an important means for diagnosis of Cryo GN, while membranous proliferative GN is the most common pathological type of Cryo GN. In recent years, great advances have been made in the treatment of Cryo Vas and its underlying diseases, and this review has briefly introduced these advances.@*Conclusions@#Laboratory examinations of serum cryoglobulins urgently need standardization. The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.

Clinical and pathological features of idiopathic membranous nephropathy with phospholipase A2 receptor negative and serum anti PLA2R antibody negative: 40 cases analysis / 中国实用内科杂志

OBJECTIVE: To investigate the clinicopathological features of phospholipase A2 receptor(PLA2R) negative patents with idiopathic membranous nephropathy(IMN). METHODS: IMN patients diagnosed by renal biopsy were enrolled in this study. Glomerular PLA2 R deposition(GAg) and serum anti-PLA2 R antibodies(SAbs) were detected by immunohistochemical staining and enzyme linked immunosorbent assay, respectively. Patients were divided into two groups. Both GAg and SAbs were negative in patients of Group A. Patients of group B were selected from patients who were positive for GAg and SAbs and were matched with group A in gender and age. The clinical and laboratory data of the two groups were collected. Glomerular thrombospondin type-1 domaincontaining 7A(THSD7A) deposition and serum anti-THSD7 A antibody were also measured by immunohistochemical staining and indirect immunofluorescence in the two groups, respectively. RESULTS:(1) Compared with group B, patients in group A had lower levels of proteinuria, lower proportion of microscopic hematuria, higher remission rate(P<0.05). The positive rate of IgG4 in group A(45.0%) was significantly lower than that in group B(85.0%)(P<0.01).(2) The positive rate of glomerular THSD7 A deposition and serum anti-THSD7 A antibody of group A were 17.5% and 7.5%. Patients in group B showed negative THSD7 A tissue staining and antiTHSD7 A antibodies. CONCLUSION: Compared with patients who were positive for GAg and SAbs, patients who were negative for GAg and SAbs exhibited lower levels of proteinuria and higher remission rate. The positive rate of glomerular THSD7 A deposition and serum anti-THSD7 A antibody was low in patients with IMN.

Purinergic 2X7 Receptor is Involved in the Podocyte Damage of Obesity-Related Glomerulopathy via Activating Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome / 中华医学杂志(英文版)

Background@#The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R). This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation of NLRP3 inflammasome.@*Methods@#A mouse model of ORG was established by high-fat diet feeding. The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079). The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3, ASC, and caspase-1, as well as the podocyte-associated molecules including nephrin, podocin, and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Western blot analysis, respectively.@*Results@#The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo, which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules. Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression of podocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro, and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.@*Conclusions@#P2X7R could trigger the activation of NLRP3 inflammasome, and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.

Arthroscopic treatment of elbow stiffness using an additional auxiliary soft-point portal / 中华创伤骨科杂志

Objective To investigate the feasibility of adding an auxiliary soft-point portal for the arthroscopic treatment of stiff elbow.Methods From January 2016 to August 2017,20 patients with stiff elbow were treated at Department of Orthopaedic Surgery,The Second Affiliated Hospital to Nanchang University.They were 13 males and 7 females,with a mean age of 30.8 years (from 18 to 46 years).Their elbow stiffness time averaged 8.4 months (from 6 to 14 months).Their stiff elbow was released by elbow arthroscopy after their surgical contraindications were controlled.In addition to conventional portals,an auxiliary soft-point portal was used.Analgesia was conducted postoperatively and staged rehabilitation encouraged immediately after operation.The therapeutic effects were evaluated using Hospital for Special Surgery (HSS) elbow score and the Mayo scoring system at final follow-ups.Results The 20 patients were followed up for an average time of 8.9 months (from 4 to 15 months).Their preoperative maximum elbow flexion (62.3°±21.4°),maximum elbow extension (30.4° ± 13.6°) and total range of elbow motion (32.5° ± 22.4°) were significantly improved to 112.6° ± 23.4°,15.3° ± 10.4° and 98.4° ± 15.3°,respectively,at final follow-ups (P ＜0.05).According to their HSS elbow scores,13 cases were excellent and 7 good,yielding an excellent to good rate of 100％;their preoperative Mayo scores (64.1 ± 12.8) were significantly improved to 85.6 ± 7.4 points at final follow-ups (P ＜ 0.05).Conclusion Addition of an auxiliary soft-point portal in the arthroscopic treatment of elbow stiffness can simplify operative maneuver and shorten operation time,leading to fine curative efficacy.

Arthroscopic treatment of avulsion fracture of tibial attachment of anterior cruciate ligament using double Endobutton plates / 中华创伤骨科杂志

Objective To explore the feasibility and curative effect of arthroscopic treatment of avulsion fracture of the tibial attachment of anterior cruciate ligament ( ACL ) using Ethibood line plus double Endobutton plates. Methods From May 2014 to January 2016, 26 cases of acute ACL tibial attachment fracture were treated surgically. They were 16 males and 10 females, aged from 9 to 45 years ( average, 26. 6 years ) . By the Meyers-McKeeve classification, there were 17 cases of type Ⅱand 9 ones of type Ⅲ. In preoperative examina-tion, their Lachman test and Anterior Drawer Test were all positive. All their bone blocks were fixated using Ethibond line plus double Endobutton plates. Results Their operative time ranged from 50 to 70 min, averaging 57 min. On average, the 26 patients obtained a follow-up of 8 months ( from 6 to 13 months ) . X-rays at 3 months after operation showed all fractures united. At the last follow-up, their Lachman test and Anterior Drawer Test were all negative. The range of motion of the knee joint was larger than 120° in all; their Lysholm score of the knee joint averaged 90. 6 ± 2. 9 points, significantly higher than their preoperative value ( 43. 6 ± 4. 7 points ) ( t=7. 583, P=0. 026 ); their International Knee Documentation Committee ( IKDC ) scores averaged 93. 1 ± 4. 2 points, significantly higher than their preoperative value ( 46. 3 ± 5. 1 points ) ( t=8. 162, P=0. 021 ) . No such complications as reflexive neural dystrophy, avascular necrosis or weak knee extension occurred during follow-ups. Conclusion The avulsion fractures of ACL tibial attachment can be treated arthroscop-ically using Ethibood line plus double Endobutton plates, because this technique has such advantages as simple operation, limited invasion, good fracture reduction, strong fixation, and possibility of early functional rehabil-itation of the knee joint.

Improvement and optimization of performance verification on enzyme linked immunosorbent assay for determination of hepatitis B markers / 国际检验医学杂志

Objective To evaluate the performance of enzyme linked immunosorbent assay (ELISA) kit in detection of Hepatitis B virus(HBV) markers by using improved and optimized method ,so as to provide a practical and feasible method and reagents for clinical laboratory .Methods ELISA test was used for the detection of HBV markers .The gradient dilution method was used to e‐valuate the lower limit .The verifiation of cut off value was carried out based on clinical and laboratory standards institute (CLSI) EP12‐A2 document .Samples with cut off values were collected to evaluate the precision ,including repeatability and intermediate precision .The coincidence rates were counted through comparing the results of ELISA with those of external quality assessment and those detected by using Abbott i4000SR chemiluminescence instrument .Results The lower detection limit of HBsAg ,HBsAb , HBeAg ,HBeAb and HBcAb were 0 .2 IU/mL ,20 mIU/mL ,1 NCU/mL ,0 .75 NCU/mL and 0 .05 NCU/mL respectively .The cut‐off value(C50 )± 20% concentration included the concentration range between C5 and C95 .The within‐run coefficient of variation (CV)≤15% ,in sandwich method the between‐run CV≤25% ,in competition method the between‐run CV≤35% .The positive and negative coincidence rates in accuracy and comparing with i 4000SR all were more than 95% and all κ>0 .75 .Conclusion ELISA tests for HBV markers in our laboratory could meet the requirements of the detection performance and clinical needs .