Not only baseline but cumulative exposure of remnant cholesterol predicts the development of nonalcoholic fatty liver disease: a cohort study

BACKGROUND AND AIM@#Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD.@*METHODS@#This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD.@*RESULTS@#After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1.@*CONCLUSION@#Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.

Da Chengqitang Protects Intestinal Barrier in Septic Mice via Endogenous Antimicrobial Peptide mCRAMP / 中国实验方剂学杂志

ObjectiveMolecular docking and animal experiments were employed to explore the protective effect and mechanism of Da Chengqitang （DCQD） on intestinal barrier in septic mice. MethodText mining method was used to screen the active ingredients in DCQD. AutoDock Tools and Discovery Studio were used to study the interactions of active components with the core target proteins ［claudin-1， tumor necrosis factor （TNF）-α， interleukin （IL）-6， endogenous antimicrobial peptide mCRAMP， Toll-like receptor 4 （TLR4）， and myeloid differentiation primary response gene 88 （MyD88）］ in sepsis. Fifty C57BL/6 mice were randomized into sham， model， low- and high-dose （4 g∙kg-1 and 8 g∙kg-1） DCQD， and ulinastatin groups （n=10）. Before， during， and after the day of modeling surgery， each group was administrated with corresponding drugs. The mice in other groups except the model group were subjected to modeling by cecal ligation and puncture. Enzyme-linked immunosorbent assay （ELISA） was used measure the serum level of D-lactic acid to assess intestinal mucosa permeability. Hematoxylin-eosin staining was employed to observe the histopathological changes in the ileum and assess the intestinal mucosal damage and inflammatory infiltration. Western blotting was employed to determine the expression levels of tight junction proteins claudin-1 and occludin in the ileal tissue， which were indicative of the bowel barrier function. The TNF-α and IL-6 levels were measured by ELISA to assess the intestinal inflammation. The expression of mCRAMP in the ileal tissue was observed by immunohistochemistry. The mRNA levels of mCRAMP， TLR4， and MyD88 in mouse ileal tissue were determined by Real-time polymerase chain reaction， on the basis of which the mechanism of DCQD in protecting the intestinal barrier of septic mice was explored. ResultMolecular docking results showed that most of the 10 active ingredients of DCQD that were screened out by text mining could bind to sepsis targets by van der Waals force， hydrogen bonding， and other conjugated systems. The results of animal experiments showed that compared with the model group， low- or high-dose DCQD lowered the D-lactic acid level in the serum （P<0.01）， alleviated damage to the ileal tissue and mucosal edema， protected the small intestine villus integrity， reduced inflammatory cell infiltration， promoted the expression of claudin-1 （P<0.01）， lowered the IL-6 level （P<0.01）， up-regulated the mRNA and protein levels of mCRAMP （P<0.01）， and down-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.01） in the ileal tissue. In addition， high-dose DCQD lowered the TNF-α level and promoted the expression of occludin in the ileum tissue （P<0.01）， and low-dose DCQD up-regulated the protein level of occludin in the ileum tissue （P<0.05）. ConclusionDCQD has a protective effect on intestinal barrier in septic mice. It can reduce intestinal inflammation， repair intestinal mucosal damage， improve the tight junction protein level， and reduce intestinal mucosal permeability by up-regulating the mRNA and protein levels of mCRAMP and the down-regulating the expression of genes in the TLR4/MyD88 pathway.

Total electric field intensity in workplace of high-voltage direct current converter stations / 环境与职业医学

Background The converter stations of high-voltage direct current (HVDC) transmission lines generate special total electric fields. At present, few investigations have been conducted on total electric fields in the workplace of converter stations from an perspective of occupational health. Objective To understand the current situation of total electric field strength in the workplace of converter stations. Methods Using purposive sampling, a calibrated HDEM-1 direct current (DC) total electric field strength measurement system was used to measure the total electric fields of 12 converter stations serving 6 DC lines in Southeast and Southwest China according to the Measurement method for total electric field strength and ion current density of the converter stations and DC transmission lines (DL/T 1089—2008). The results were evaluated according to occupational exposure limits recommended by The limits of electromagnetic environment at ±800 kV UHV DC converter station (DL/T 275—2012), the American Conference of Governmental Industrial Hygienists (ACGIH), and the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Results A total of 615 check points were planned, the total electric field strength was 0.05-37.05 kV·m−1, and the median was 10.45 kV·m−1. The total electric field strength of 39 check points (6.3%) exceeded 25 kV·m−1 (the limits of ACGIH and ICNIRP), and the total electric field strength of 12 check points (2.0%) exceeded 30 kV·m−1 (the limit of DL/T 275—2012). There were statistically significant differences in the total electric field strength values and the proportions of exceeding 25 kV·m−1 between the neutral regions and the positive regions and between the neutral regions and the negative regions (P < 0.01). The proportion of total electric field strength exceeding 30 kV·m−1 in the negative regions was higher than that in the positive regions (P < 0.01). There were no significant differences in the total electric field strength of converter stations at different voltage levels and different altitudes (P > 0.05). There were no significant differences in the proportions of total electric field exceeding 25 kV·m−1 and exceeding 30 kV·m−1 in converter stations at different voltage levels and different altitudes (P > 0.05). Conclusion The total electric field in some workplace of converter stations exceeds selected limits. Converter station operators may be exposed to high-strength total electric field for a short time.

Clinical, genetic, and pathological analysis in 165 children with disorders of sex development / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD).@*METHODS@#A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022.@*RESULTS@#Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants.@*CONCLUSIONS@#Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.

Silencing of SMAD family member 3 promotes M2 polarization of macrophages and the expression of SMAD7 in rheumatoid arthritis / 细胞与分子免疫学杂志

Objective To investigate the effect of SMAD family member 3(SMAD3) silenced by small interfering RNA (siRNA) on macrophage polarization and transforming growth factor β1 (TGF-β1)/ SMAD family signaling pathway in rheumatoid arthritis (RA). Methods RA macrophages co-cultured with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were used as a cell model. TGF-β1 was used to stimulate macrophages, and SMAD3-specific siRNA (si-SMAD3) and negative control siRNA (si-NC) were transfected into human RA macrophages co-cultured in TranswellTM chamber. The expression of SMAD3 mRNA was detected by real-time fluorescence quantitative PCR, and the expression of TGF-β1, SMAD3 and SMAD7 protein was detected by Western blot analysis. The contents of TGF-β1 and IL-23 in cell culture supernatant were determined by ELISA. Cell proliferation was detected by CCK-8 assay. TranswellTM chamber was used to measure cell migration. Results Compared with the model group and the si-NC group, the expression of TGF-β1, SMAD3 mRNA and protein in RA macrophages decreased significantly after silencing SMAD3. In addition, the secretion of IL-23 decreased significantly, and the cell proliferation activity and cell migration were inhibited, with high expression of SMAD7. Conclusion Knockdown of SMAD3 can promote M2 polarization and SMAD7 expression in RA macrophages.

Clinical characteristics and genetic analysis of two children with Tuberous sclerosis complex / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic variants in two children with Tuberous sclerosis complex (TSC).@*METHODS@#Two children who had presented at the Children's Hospital Affiliated to Zhengzhou University respectively in June 2020 and July 2021 were selected as the study subjects. Clinical data of the children were collected, and potential pathogenic variants were screened by whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of their family members.@*RESULTS@#Child 1 was a 7-month-and-29-day-old male, and child 2 was a 2-year-and-6-month-old male. Both children had shown symptoms of epileptic seizures and multiple hypomelanotic macules. Genetic testing revealed that both children had harbored de novo variants of the TSC2 gene, namely c.3239_3240insA and c.3330delC, which were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as pathogenic (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#This study has uncovered the genetic etiology for two children with TSC. Above findings have also enriched the phenotypic and mutational spectrum of TSC in the Chinese population.

Analysis of CLCN4 gene variant in a child with Raynaud-Claes syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS).@*METHODS@#A child who was diagnosed with RCS at the Children's Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed.@*RESULTS@#The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#The c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.

Analysis of clinical phenotypes and MMACHC gene variants in 65 children with Methylmalonic acidemia and homocysteinemia / 中华医学遗传学杂志

OBJECTIVE@#To carry out Sanger sequencing for MMACHC gene variants among 65 Chinese pedigrees affected with combined methylmalonic aciduria and homocysteinemia, and summarize their genetic and clinical characteristics and prognosis.@*METHODS@#Clinical characteristics of the 65 children identified with Methylmalonic acidemia and homocysteinemia at the Children's Hospital Affiliated to Zhengzhou University (Zhengzhou Children's Hospital) from April 2017 to April 2022 were selected as the study subjects. Potential variants of the MMACHC gene were detected by direct sequencing of the PCR products.@*RESULTS@#The median age of the 65 children was 3 months (14 days to 17 years old). These included 28 cases (43.08%) from neonatal screening, 11 cases (16.92%) with a history of jaundice, and 9 cases (13.85%) with various degrees of anemia. The main clinical symptoms included development delay, slow growth, epilepsy, hydrocephalus, lethargy, feeding difficulty, regression or decline in motor ability, recurrent respiratory infections, anemia, jaundice, respiratory and heart failures, hydrocephalus, limb weakness, and hypertension. Blood and urine tandem mass spectrometry screening has revealed increase of methylmalonic acid, propionyl carnitine, propionyl carnitine/acetylcarnitine ratio, and propionyl carnitine/free carnitine ratio to various extents, and blood homocysteine was increased in all patients. The detection rate of genetic variants was 98.46% (128/130), and in total 22 types of MMACHC gene variants were detected. The most common ones have included c.609G>A (W203X) (58/128), c.658-660del (K220del) (19/128), and c.80A>G (Q27A) (16/128). Two novel variants have been identified, namely c.565C>T (p.R189C) and c.624_ 625delTG (p.A208Afs), which were respectively predicted as likely pathogenic (PM2_Supporting+PM3+PP2+PP3) and pathogenic (PVS1+PM2_Supporting+PM3+PP2) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Exon 4 had the highest frequency for the detection.@*CONCLUSION@#Identification of MMACHC gene variants has confirmed the diagnosis in the children, among which the c.609G>A variant has the highest frequency. Discovery of the new variants has enriched the mutational spectrum of the MMACHC gene.

Clinical and genetic analysis of children with developmental and epileptic encephalopathy 8 caused by ARHGEF9 gene variants / 中华神经科杂志

Objective:To analyze the clinical characteristics and genetic variation of 2 children with developmental and epileptic encephalopathy 8 (DEE8).Methods:Whole-exome sequencing (WES) was performed to determine the potential variants in the probands. Candidate variants identified by WES were validated by Sanger sequencing and quantitative real-time polymerase chain reaction. X chromosome inactivation (XCI) detection was performed in the proband 1′s mother and proband 2 to detect the allelic expression difference of ARHGEF9. Results:Both of the cases showed global developmental delay. Proband 1 presented with delayed motor and speech development, intellectual disability, and seizures. Electroencephalography of proband 1 showed slow background activity, with spikes, spike and waves in bilateral frontal and midline regions during sleep. While proband 2 showed delay in acquisition of language, motor skills, and cognition, but no seizures. It was identified that proband 1 carried a novel maternally derived heterozygous splicing variant (c.925-2A>T) in ARHGEF9 by WES, which was verified in Sanger sequencing. The XCI in proband 1′s mother was observed, and the expression ratio of mutant ARHGEF9 and wild-type was 0∶100%. A novel exon 3-10 heterozygous deletion of ARHGEF9 was identified in proband 2, and this variant was not found in his unaffected parents. Conclusions:DEE8 disorders are relatively rare. Most of the patients have varying degrees of neurodevelopmental phenotype, but epilepsy is not a specific clinical manifestation. ARHGEF9 gene deletion and splicing variation may be the genetic cause of the 2 probands, and above findings have enriched the spectrum of variation and phenotype of DEE8.

Mechanism of mesenchymal stem cell-derived exosome for alleviating hepatic ischemia-reperfusion injury / 中华器官移植杂志

The review focuses upon the mechanism of exosome derived from mesenchymal stem cells in hepatic ischemia-reperfusion injury(IRI)to provide references for clinical application of exosomes in alleviating hepatic IRI.

Clinical trial of low-dose rabbit anti-human thymocyte globulin for induction therapy of kidney transplantation in children / 中华器官移植杂志

Objective:To explore the efficacy and safety of low-dose rabbit anti-human thymocyte globulin (rATG) for induction therapy of kidney transplantation (KT) in children.Methods:From October 2018 to May 2021, clinical data were reviewed retrospectively for 77 pediatric KT recipients on a low-dose rATG induction protocol.Recipient/graft survival rate, renal function recovery, acute rejection (AR) and adverse reactions were observed at 1 year post-operation.The postoperative changes of renal function were examined by Friedman’s test; According to the preoperative baseline data, Pearson’s Chi-square or Fisher's exact test was utilized for examining the influencing factors of postoperative AR.Results:A total of 16(20.78%) recipients had AR within the first 6 months post-operation.The incidence of delayed graft function (DGF) was 14.29%(11/77); The incidence of severe infection post-transplantation 18.18%(14/77), the infection rate of BK virus 25.97%(20/77) and the incidence of neutropenia 32.47%(25/77).The recipient/graft survival rate at 1 year post-operation was 97.40%(75/77) and 94.81%(73/77) respectively.Chi-square test indicated that the incidence of postoperative infection in children with body weight ≤30 kg and height ≤138 cm was 28.95%(11/38) and 27.50%(11/40) respectively, Both were higher than 7.69%(3/39) and 8.11%(3/37) of children with body weight >30 kg and height>138 cm.The difference between groups was statistically significant ( P=0.016 and 0.028). Conclusions:Low-dose rATG is generally excellent in preventing AR in pediatric KT recipients.And the risk of related AR may be lower.The infection rate of recipients with decent preoperative development is low.

Safety and clinical outcomes of thoracoscopic segmentectomy in bilateral lung cancer: A single-center retrospective study / 中国胸心血管外科临床杂志

@#Objective     To assess the safety and clinical outcomes of segmentectomy in one- or two-staged video-assisted thoracoscopic surgery (VATS) for bilateral lung cancer. Methods    We retrospectively enrolled 100 patients who underwent VATS segmentectomy for bilateral lung cancer at the Department of Thoracic Surgery of Peking Union Medical College Hospital from December 2013 to May 2022. We divided the patients into two groups: a one-stage group (52 patients), including 17 males and 35 females with a mean age of 55.17±11.09 years, and a two-stage group (48 patients), including 16 males and 32 females with a mean age of 59.88±11.48 years. We analyzed multiple intraoperative variables and postoperative outcomes. Results     All 100 patients successfully completed bilateral VATS, and at least unilateral lung received anatomical segmentectomy. Patients in the one-stage group were younger (P=0.040), had lower rate of comorbidities (P=0.030), were less likely to have a family history of lung cancer (P=0.018), and had a shorter interval between diagnosis and surgery (P=0.000) compared with patients in the two-stage group. Wedge resection on the opposite side was more common in the one-stage group (P=0.000), while lobectomy was more common in the two-stage   group. The time to emerge from anesthesia in the one-stage group was longer than that in the first and second operations of the two-stage group (P=0.000, P=0.002). Duration of surgery and anesthesia were similar between two groups (P>0.05). Total number of lymph node stations for sampling and dissection (P=0.041) and lymph nodes involved (P=0.026) were less in the one-stage group. Intraoperative airway management was similar between two groups (P>0.05). The one-stage group was associated with lower activities of daily living (ADL) scores. Conclusion     Segmentectomy is safe in one- or two-staged VATS for bilateral lung cancer, including contralateral sublobectomy and lobectomy. Duration of surgery and perioperative complications are similar between two groups, but the one-stage group is associated with lower ADL scores. On the basis of comprehensive consideration in psychological factors, physical conditions and personal wishes of patients, one-staged sequential bilateral VATS can be the first choice.

Application of Modified Intraoperative Axillary Fluoroscopy for Posterior Acromioclavicular Joint Dislocation / 中山大学学报(医学科学版)

ObjectiveThe study aims to determine whether the horizontal posterior displacement of the distal clavicle in patients with acromioclavicular joint dislocation can be corrected via the application of modified intraoperative axillary fluoroscopy. MethodsFrom February 2019 to April 2021， 50 patients with Rockwood type Ⅲ acromioclavicular joint dislocation eligible for inclusion were randomly divided into two groups： the normal （32 cases） and the experimental （18 cases）. The conventional anteroposterior position radiographs were obtained to detect the surgery effect on the patients in the normal group. In experimental group， modified intraoperative axillary radiographs were obtained， with the concept of polar coordinates introduced to reduce the horizontal posterior translation of the clavicle. Then we compared the perioperative parameters， such as average operative time， intraoperative blood loss between the two groups. The Constant score was used for assessing the postoperative function of the shoulder joint in the follow-up visits. ResultsNo statistically significant difference was found in gender， age， duration of injury， underlying diseases， intraoperative blood loss and operative time between the two groups. The postoperative shoulder function score of the experimental group was higher than that of the normal group. ConclusionsThe application of modified intraoperative axillary fluoroscopy is recommendable for accurately reducing posterior translation of the distal clavicle， and meanwhile helpful for the precise placement of the clavicular plate.

Observation on the efficacy of moderate and high myopia patients with vault greater than 1 000 μm after implantation of phakic posterior chamber implantable contact lens / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the efficacy of moderate and high myopia patients with vault greater than 1 000μm after implantation of phakic posterior chamber implantable contact lens(ICL).METHODS: A total of 42 patients(73 eyes)who received ICL implantation in the hospital and had postoperative vault greater than 1 000 μm between January 2014 and January 2017 were selected and retrospectively studied. Changes in visual acuity, intraocular pressure, corneal endothelial cell density, anterior chamber-related parameters(chamber angle, central anterior chamber depth, anterior chamber volume)and vault were compared among patients before surgery, at 1, 3, 6mo and 1a after surgery and at the last follow-up.RESULTS: The uncorrected visual acuity(UCVA)at 1, 3, 6mo and 1a after surgery and at the last follow-up was better than that before surgery(all P&#x0026;#x003C;0.05), and the chamber angle, central anterior chamber depth and anterior chamber volume were smaller or lower than those before surgery(all P&#x0026;#x003C;0.05), but there were no statistical differences in UCVA, chamber angle, central anterior chamber depth and anterior chamber volume at each time point after surgery(all P&#x0026;#x003E;0.05). The intraocular pressure at 1mo after surgery was lower than that before surgery(P&#x0026;#x003C;0.05), but the intraocular pressure at 3, 6mo and 1a after surgery and at the last follow-up was not statistically different from that before surgery(all P&#x0026;#x003E;0.05). There was no statistical significance in the corneal endothelial cell density at 1, 3, 6mo and 1a after surgery and at the last follow-up compared with that before surgery(all P&#x0026;#x003E;0.05). The vault at 1, 3, 6mo and 1a after surgery and at the last follow-up showed a decreasing trend, and the difference was statistically significant at each time point after surgery(all P&#x0026;#x003C;0.05).CONCLUSION: The short-term and long-term efficacy are better in moderate and high myopia patients with vault greater than 1 000 μm after ICL implantation, and there are no significant effects on the intraocular pressure and corneal endothelial cell. The postoperative anterior chamber structure is relatively stable and the vault tends to decrease over time. In most cases, close observation is sufficient and intraocular lens replacement is generally not required.

Clinical characteristics and prognosis of acute on chronic liver failure in patients with recompensatory hepatitis B cirrhosis / 临床肝胆病杂志

Objective To assess the clinical characteristics of acute-on-chronic liver failure in patients with recompensatory hepatitis B cirrhosis. Methods A total of 180 patients with acute-on-chronic liver failure hospitalized in Tianjin Third Central Hospital from September 2013 to September 2021 were retrospectively collected, with 110 patients had compensatory hepatitis B cirrhosis and 70 patients had compensatory hepatitis B cirrhosis and used as the control. Their causes, clinical biochemical indicators, complication rate, and prognosis were compared. The Chi-square test or Fisher's exact test was used for comparison of categorical variables between groups, and the Mann-Whitney U test was performed for analysis of the continuous variables. Kaplan-Meier curves and Log-rank test were used for survival of patients. Results The incidence of hepatorenal syndrome ( χ 2 =4.618, P =0.032), infection ( χ 2 =6.712, P =0.010), Cr ( Z =-4.508, P < 0.001), and PCT ( Z =-2.052, P =0.040) were all higher, whereas GGT ( Z =-2.042, P =0.041), Na ( Z =-2.001, P =0.045), FBS ( Z =-3.065, P =0.002), and TC ( Z =-4.268, P < 0.001) were all lower in the recompensation group than in the control group of patients. However, 90-day mortality rate ( χ 2 =3.366, P =0.067) and 1-year mortality rate ( χ 2 =1.893, P =0.169), 90-day survival ( χ 2 =2.68, P =0.100), and 1-year survival ( χ 2 =2.074, P =0.150) were not statistically significant difference. Conclusion Compared with compensatory hepatitis B cirrhosis, patients with recompensatory cirrhosis had an increased risk in developing hepatorenal syndrome, infection, and increased creatinine level after acute-on-chronic liver failure, although there was no statistically significant difference in 90-days and 1-year survival of patients.

Analysis of the risk factors for poor prognosis and recurrence in patients with anti-NMDAR encephalitis / 中华预防医学杂志

To investigate the risk factors of poor prognosis and recurrence in patients with anti-NMDAR encephalitis. A single center, observational cohort study was used to retrospectively analyze 44 patients with anti NMDAR encephalitis hospitalized in the Department of Neurology of Beijing Tong Ren Hospital from January 2014 to October 2020. The results showed that the interval from onset to immunotherapy in the poor prognosis group was significantly longer than that in the good prognosis group (t=2.045,P=0.047), and the course of disease in the poor prognosis group was significantly longer than that in the good prognosis group (t=4.127,P=0.000 2). The number of patients with clinical manifestations of dyskinesia was significantly increased (Fisher exact test: P=0.014). The patients with abnormal brain MRI in the poor prognosis group were significantly more than those in the good prognosis group (Fisher exact test: P=0.017), and the patients with slow wave>50% in the poor prognosis group were significantly more than those with slow wave <50% (Fisher exact test: P<0.001). Patients with the first onset of immunotherapy time <3 months, long course of disease, high intracranial pressure, and high cerebrospinal fluid protein are prone to relapse. Bivariate logistic regression analysis showed that patients with dyskinesia, abnormal brain MRI, and slow wave EEG more than 50% were risk factors for poor prognosis (OR values were 4.687, 4.978, and 24.500, respectively; P values were 0.018, 0.016, and 0.000, respectively). The time of first-line immunotherapy for the first onset<3 months was the risk factor for recurrence (OR 17.231, P=0.010). In conclusion, dyskinesia, abnormal brain MRI and slow wave of EEG more than 50% may be the risk factors for poor prognosis of patients. The duration of immunotherapy less than 3 months after the first onset might be the risk factor for recurrence.

Current status and outlook of medical treatment for KRAS-mutated non-small cell lung cancer / 中华肿瘤杂志

Lung cancer remains the leading cause of cancer-related deaths in men and women worldwide, and 85% of these patients have non-small cell lung cancer. In recent years, the clinical use of targeted drug therapy and immune checkpoint inhibitors has dramatically changed the treatment landscape for advanced NSCLC. The mechanism and the value of targeted therapies have been a hot topic of research, as KRAS is one of the earliest discovered and most frequently mutated oncogenes, which is activated by binding to GTP and triggers a series of cascade reactions in cell proliferation and mitosis. The KRAS protein acts as a molecular switch and is activated by binding to GTP, triggering a series of cascade responses in cell proliferation and mitosis. Clinically, patients with KRAS mutated NSCLC have poor response to systemic medical therapy and poor prognosis. Since the first report of KRAS gene in 1982, research on KRAS targeted therapeutics has been slow, and previous studies such as farnesyltransferase inhibitors and downstream protein inhibitors of KRAS signaling pathway have not achieved the expected results, making KRAS long defined as a "non-druggable target". The deeper understanding of the crystal structure of KRAS has led to the discovery of potential therapeutic sites for KRAS and the development of several drugs directly targeting KRAS, especially KRAS G12C inhibitors such as AMG510 (sotorasib) and MRTX849 (adagrasib), which have shown encouraging results in clinical trials. In recent years, studies on the therapeutic efficacy of immune checkpoint inhibitors for KRAS-mutated NSCLC have made some progress. In this review, we systematically introduce the basic understanding of RAS gene and clinical characteristics of KRAS mutated NSCLC patients, summarize the medical treatments for KRAS mutated NSCLC, including chemotherapy, anti-vascular drug therapy and tumor immunotherapy, and focus on the review and outlook of the research progress of KRAS targeted therapy.

Preliminary analysis of qualitative changes in suspended red blood cells under different low-pressure and hypoxic conditions / 中国输血杂志

【Objective】 To evaluate the quality of suspended red blood cells (SRBC) under low-pressure and hypoxic conditions, in order to lay a theoretical foundation for airline delivery, air drop and storage of SRBC on plateau. 【Methods】 The low-pressure and hypoxic conditions (0.026 MPa and 0.047 MPa) were simulated by a pressure control device. SRBC were divided into 3 groups (5 bags/group, 1.5 U/bag). Each group was stored in 0.026 MPa environment at 2℃-6℃ for 24 hours (named 0.026 MPa), in 0.047MPa environment at 2℃-6℃ for 7 days (named 0.047 MPa), and in a blood storage refrigerator at 4℃ (named the control), respectively. The storage cell characteristics were examined on day 2, 9, 14, 28 and 35. 【Results】 We found that HCT, MCV, K+, Na+, FHb, hemolytic ratio, 2, 3-DPG and rheological properties in group 0.026 MPa and 0.047 MPa were not significant different compared with that in control (P>0.05). The consumptions of Glu in group 0.026 MPa and 0.047 MPa were significantly higher (P<0.05), and a transient increase in LAC concentration of group 0.026 MPa and 0.047MPa were observed, compared to the control. 【Conclusion】 The conditions of low-pressure and hypoxia have no significant effect on the quality of suspended red blood cells.

Mechanical Thrombectomy for Refractory Cerebral Venous Sinus Thrombosis in a Child with Nephrotic Syndrome : A Case Report

Nephrotic syndrome (NS) is associated with cerebral venous sinus thrombosis (CVST), which is a rare cerebrovascular disorder in children. Systemic anticoagulation with heparin is the standard therapy for CVST, and mechanical thrombectomy (MT) has been described as a salvage treatment for adult anticoagulant refractory CVST, However, it has never been reported in children. We describe a case of MT for refractory CVST in a child with NS. A 13-year-old boy with newly diagnosed NS presented to an emergency department with acute headache. A head computed tomography showed acute thrombus in the superior sagittal sinus, straight sinus and transverse sinus. The child was started on heparin therapy, but clinically deteriorated and became unresponsive. In view of the rapid deterioration of the condition after anticoagulation treatment, the patient received intravascular treatment. Several endovascular technologies, such as stent retriever and large bore suction catheter have been adopted. After endovascular treatment, the patient’s neurological condition was improved within 24 hours, and magnetic resonance venography of the head demonstrated that the CVST was reduced. The child recovered with normal neurological function at discharge. This case highlights the importance of considering MT for refractory CVST, and we suggest that MT may be considered for refractory CVST with NS in children.

Research progress of IRE1α inhibitors / 药学学报

Inositol requiring enzyme 1 alpha (IRE1α), a widespread transmembrane protein in mammals, is an endoplasmic reticulum stress (ER stress) receptor. Among the three signaling pathways of the unfolded protein response (UPR), the IRE1α pathway is the most conservative. And there is a growing body of evidence that the occurrence and development of tumors is closely related to the over-expression of IRE1α. Therefore, the study of the IRE1α inhibitors is of great significance to the discovery of new anti-tumor drugs and has been attracting more and more attention. In the hope of providing ideas for the research of targeting IRE1α for cancer therapy, this paper reviewed the data of representative IRE1α inhibitors, including inhibitory activity, the mechanism of action, structural characteristics, and so on.