A decade of liver transplantation in Mongolia: Economic insights and cost analysis.

BACKGROUND: Mongolia introduced liver transplantation 10 years ago, becoming the 46th country globally to successfully perform this procedure. However, the cost of liver transplantation treatment remains expensive in Mongolia, a lower-middle-income country. Thus, the need to calculate the cost of liver transplants, a highly-valued treatment, forms the basis for this study. METHODS: This study employed a retrospective research design with secondary data. The primary dataset comprised 143 cases of liver transplantation performed at the First Central Hospital of Mongolia between 2011 and 2021. RESULTS: The average cost of a liver transplant in Mongolia is $39,589 ± 10,308, with 79.6% being direct costs and 20.4% indirect costs. Of the direct costs, 71% were attributed to drugs, medical equipment, and supplies, while 8.6% accounted for salaries. In terms of the Model of End-Stage Liver Disease (MELD) scores, treatment costs were $39,205 ± 10,786 for patients with MELD ≤ 14 points, $40,296 ± 1,517 for patients with MELD 15-20 points, $39,352 ± 8,718 for patients with MELD 21-27 points, and $39,812 ± 9,954 for patients with MELD ≤ 28 points, with no statistically significant difference (P = 0.953). However, when calculated according to the Child-Turcotte-Pugh (CTP) score classification, treatment cost for CTP-A patients was $35,970 ± 6,879, for CTP-B patients $41,951 ± 12,195, and for CTP-C patients $37,396 ± 6,701, which was statistically significant (Р=0.015). CONCLUSION: The average cost of liver transplantation treatment in Mongolia was $39,589. Despite medical facilities' capacity to treat up to 50 patients annually, the waiting list exceeds 300 individuals, highlighting significant unmet healthcare needs.

Cumulative exposure to AHA Life's Essential 8 is associated with nonalcoholic fatty liver disease: a large cohort study.

BACKGROUND AND AIM: We aimed to explore the associations of baseline and cumulative cardiovascular health with nonalcoholic fatty liver disease (NAFLD) development and regression using the new Life's Essential 8 score. METHODS: From a health screening database, participants who underwent at least 4 health examinations between 2012 and 2022 were recruited and categorized into two cohorts: (a) the NAFLD development cohort with no history of NAFLD prior to Exam 4 and (b) the NAFLD regression cohort with diagnosed NAFLD prior to Exam 4. The LE8 score was calculated from each component. The outcomes were defined as newly incident NAFLD or regression of existing NAFLD from Exam 4 to the end of follow-up. RESULTS: In the NAFLD development cohort, of 21,844 participants, 3,510 experienced incident NAFLD over a median follow-up of 2.3 years. Compared with the lowest quartile of cumulative LE8, individuals in the highest quartile conferred statistically significant 76% lower odds (hazard ratio [HR] 0.24, 95% confidence interval [CI], 0.21-0.28) of NAFLD incidence, and corresponding values for baseline LE8 were 42% (HR 0.58, 95% CI 0.53-0.65). In the NAFLD regression cohort, of 6,566 participants, 469 experienced NAFLD regression over a median follow-up of 2.4 years. Subjects with the highest quartile of cumulative LE8 had 2.03-fold (95% CI, 1.51-2.74) higher odds of NAFLD regression, and corresponding values for baseline LE8 were 1.61-fold (95% CI, 1.24-2.10). CONCLUSION: Cumulative ideal cardiovascular health exposure is associated with reduced NAFLD development and increased NAFLD regression. Improving and preserving health behaviors and factors should be emphasized as an important part of NAFLD prevention and intervention strategies.

Bioinformatics Study on Mechanism of Postnatal Development of Craniofacial Bone.

OBJECTIVE: The postnatal development of craniofacial bone plays a crucial role in shaping the overall structure and functionality of the skull and face. Understanding the underlying mechanisms of this intricate process is essential for both clinical and research purposes. In this study, the authors conducted a bioinformatics analysis using the Gene Expression Omnibus database to investigate the molecular pathways and regulatory networks involved in the postnatal development of craniofacial bone. METHODS: In this study, the online Gene Expression Omnibus microarray expression profiling data set GSE27976 was used to identify differentially expressed genes (DEGs) in different age groups. Protein-Protein Interaction network analyses, functional enrichment, and hub genes analysis were performed. The differences in immune infiltration and microenvironment among different types of cells were also analyzed. RESULTS: In total, 523 DEGs, including 287 upregulated and 236 downregulated genes, were identified. GO and KEGG analysis showed that the DEGs were significantly enriched in multiple signaling pathways, such as skeletal system morphogenesis, osteoblast differentiation, and stem cell differentiation. Immune infiltration and microenvironment characteristics analysis showed that there were significant differences in fibroblasts, mesenchymal stem cell, osteoblast, stroma score, and microenvironment score between the two groups. Five hub genes, including IGF1, IL1B, ICAM1, MMP2 , and brain-derived neurotrophic factor, were filled out. CONCLUSION: The findings of this study showed a significant shift in gene expression towards osteogenesis during the first 12 months after birth. These findings emphasize the critical role of the postnatal period in craniofacial bone development and provide valuable insights into the molecular mechanisms underlying this process.

Critical Knowledge Gaps and Future Priorities Regarding the Intestinal Barrier Damage After Traumatic Brain Injury.

The analysis aims to provide a comprehensive understanding of the current landscape of research on the Intestinal barrier damage after traumatic brain injury (TBI), elucidate specific mechanisms, and address knowledge gaps to help guide the development of targeted therapeutic interventions and improve outcomes for individuals with TBI. A total of 2756 relevant publications by 13,778 authors affiliated within 3198 institutions in 79 countries were retrieved from the Web of Science. These publications have been indexed by 1139 journals and cited 158, 525 references. The most productive author in this field was Sikiric P, and the University of Pittsburgh was identified as the most influential institution. The United States was found to be the leading country in terms of article output and held a dominant position in this field. The International Journal of Molecular Sciences was identified as a major source of publications in this area. In terms of collaboration, the cooperation between the United States and China was found to be the most extensive among countries, institutions, and authors, indicating a high level of influence in this field. Keyword co-occurrence network analysis revealed several hotspots in this field, including the microbiome-gut-brain axis, endoplasmic reticulum stress, cellular autophagy, ischemia-reperfusion, tight junctions, and intestinal permeability. The analysis of keyword citation bursts suggested that ecological imbalance and gut microbiota may be the forefront of future research. The findings of this study can serve as a reference and guiding perspective for future research in this field.

Proteomics on human cerebral cavernous malformations reveals novel biomarkers in neurovascular dysfunction for the disease pathology.

BACKGROUND: Cerebral cavernous malformation (CCM) is a disease associated with an elevated risk of focal neurological deficits, seizures, and hemorrhagic stroke. The disease has an inflammatory profile and improved knowledge of CCM pathology mechanisms and exploration of candidate biomarkers will enable new non-invasive treatments. METHODS: We analyzed protein signatures in human CCM tissue samples by using a highly specific and sensitive multiplexing technique, proximity extension assay. FINDINGS: Data analysis revealed CCM specific proteins involved in endothelial dysfunction/inflammation/activation, leukocyte infiltration/chemotaxis, hemostasis, extracellular matrix dysfunction, astrocyte and microglial cell activation. Biomarker expression profiles matched bleeding status, especially with higher levels of inflammatory markers and activated astrocytes in ruptured than non-ruptured samples, some of these biomarkers are secreted into blood or urine. Furthermore, analysis was also done in a spatially resolving manner by separating the lesion area from the surrounding brain tissue. Our spatial studies revealed that although appearing histologically normal, the CCM border areas were pathological when compared to control brain tissues. Moreover, the functional relevance of CD93, ICAM-1 and MMP9, markers related to endothelial cell activation and extracellular matrix was validated by a murine pre-clinical CCM model. INTERPRETATION: Here we present a novel strategy for proteomics analysis on human CCMs, offering a possibility for high-throughput protein screening acquiring data on the local environment in the brain. Our data presented here describe CCM relevant brain proteins and specifically those which are secreted can serve the need of circulating CCM biomarkers to predict cavernoma's risk of bleeding.

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.

Dimension-variable invariant imbedding (DVIIM) T-matrix computational method for the light scattering simulation of atmospheric nonspherical particles.

The invariant imbedding (IIM) T-matrix method has shown great potential in light scattering field. However, the T-matrix need to be calculated through the matrix recurrence formula derived from the Helmholtz equation, thus its computational efficiency is much lower than Extended Boundary Condition Method (EBCM). To alleviate this problem, the Dimension-Variable Invariant Imbedding (DVIIM) T-matrix method is presented in this paper. Compared with the traditional IIM T-matrix model, the dimensions of the T-matrix and relevant matrices are gradually increasing as the iteration performed step by step, thus the unnecessary operations of large matrices can be avoided in early iterations. To optimally determine the dimension of these matrices in each iterative calculation, the spheroid-equivalent scheme (SES) is also proposed. The effectiveness of the DVIIM T-matrix method is validated from the modeling accuracy and calculation efficiency. The simulation results show that compared with traditional T-matrix method, its modeling efficiency can be improved notably, especially for the particles with large size and aspect ratio, where for the spheroid with a aspect ratio of 0.5, the computational time is cut down by 25%. Though the dimension of the T matrix is cut down in the early iterations, the computational precision of DVIIM T-matrix model is not decreased notably, and a good agreement is achieved between the calculation results of DVIIM T-matrix method, IIM T-matrix method and other well-validated models (like EBCM and DDACSAT), where the relative errors of the integral scattering parameters (e.g., extinction, absorption, scattering cross sections) are generally less than 1%.

Grid-adaptive Fourier pseudospectral time domain model for the light scattering simulation of atmospheric nonspherical particles.

PSTD (pseudospectral time domain) is recognized as one of the powerful models to accurately calculate the scattering properties of nonspherical particles. But it is only good at the computation in coarse spatial resolution, and large "staircase approximation error" will occur in the actual computation. To solve this problem, the variable dimension scheme is introduced to improve the PSTD computation, in which, the finer grid cells are set near the particle's surface. In order to ensure that the PSTD algorithm can be performed on non-uniform grids, we have improved the PSTD with the space mapping technique so that the FFT algorithm can be implemented. The performance of the improved PSTD (called "IPSTD" in this paper) is investigated from two aspects: for the calculation accuracy, the phase matrices calculated by IPSTD are compared with those well tested scattering models like Lorenz-Mie theory, T-matrix method and DDSCAT; for computational efficiency, the computational time of PSTD and IPSTD are compared for the spheres with different sizes. From the results, it can be found that, the IPSTD scheme can improve the simulation accuracy of phase matrix elements notably, especially in the large scattering angles; though the computational burden of IPSTD is larger than that of PSTD, its computational burden does not increase substantially.

A single-center retrospective study on epidemiological and Traditional Chinese Medicine syndrome characteristics of 21010 patients with reflux/heartburn symptoms.

OBJECTIVE: To provide a basis for the clinical identification of true and false reflux, integrated traditional Chinese and Western medicine, and psychosomatic treatment, we conducted a retrospective study of the etiology and epidemiological and Traditional Chinese Medicine (TCM) syndrome characteristics of patients with reflux/heartburn symptoms. METHODS: The 210 10 patients with reflux/heartburn treated at Tianjin Nankai Hospital from January 1, 2016, to December 31, 2019, were divided into four groups according to their pathogenesis. Sex, age, course of disease, incidence rate, gastroscopy, 24-h pH-impedance, esophageal manometry, Hamilton Anxiety Scale (HAMA) / Hamilton Depression Scale (HAMD) score, 8-week proton pump inhibitor (PPI) treatment effect, and TCM syndrome characteristics were statistically analyzed. RESULTS: A total of 21010 patients (8864 men and 12146 women), with reflux/heartburn symptoms were screened, including 6284 (29.9%) patients with reflux esophagitis (RE), 10427 (49.6%) patients with non-erosive reflux esophagitis (NERD), 2430 (11.6%) patients with reflux hypersensitivity (RH), and 1870 (8.9%) patients with functional heartburn (FH). The incidence of the disease was higher in women than in men (0.0001). The ranking of the incidence of anxiety and depression in these four groups was FH>RH>NERD>RE ( 0.0001). There were more women than men in the groups with anxiety and more men than women in the groups with depression ( 0.0001), and there was no significant difference in the distribution of anxiety and depression between men and women ( 0.5689). There were significant differences in TCM syndrome characteristics between NERD, RE, and functional esophageal diseases ( 0.01). The highest proportion of functional esophageal disease TCM symptoms was stagnation and phlegm obstruction syndrome (36.16%), and there was no significant difference between RH and FH. The effective rates of PPI treatment at 8 weeks in patients in the RE, NERD, RH, and FH groups were 89%, 72%, 54%, and 0%, respectively. RE was classified into grades A, B, C, and D according to the Los Angeles grading system. The ranking of the incidence of these four grades was A>B>C>D ( 0.0001). The effective rates of PPI treatment at 8 weeks were 91%, 81%, 69%, and 63% in patients with grade A, B, C, and D RE, respectively ( 0.0001). The highest proportion of TCM syndrome types of NERD and RE was the stagnated heat syndrome in the liver and stomach syndrome, 38.99% and 33.90%, respectively. CONCLUSION: Reflux/heartburn symptoms are relatively common in middle-aged women, and NERD is the most common etiology, followed by RE, RH, and FH. The most common TCM syndrome characteristics in NERD and RE were stagnated heat syndrome in the liver and stomach syndrome, and stagnation and phlegm obstruction syndrome in functional esophageal diseases. Most patients with reflux/heartburn symptoms also experienced anxiety and depression.

Genotype-phenotype characteristics and baseline natural history of Chinese myelin protein zero gene related neuropathy patients.

BACKGROUND AND PURPOSE: The aim was to characterize the phenotypic and genotypic features of myelin protein zero (MPZ) related neuropathy and provide baseline data for longitudinal natural history studies or drug clinical trials. METHOD: Clinical, neurophysiological and genetic data of 37 neuropathy patients with MPZ mutations were retrospectively collected. RESULTS: Nineteen different MPZ mutations in 23 unrelated neuropathy families were detected, and the frequency of MPZ mutations was 5.84% in total. Mutations c.103_104InsTGGTTTACACCG, c.513dupG, c.521_557del and c.696_699delCAGT had not been reported previously. Hot spot mutation p.Thr124Met was detected in four unrelated families, and seven patients carried de novo mutations. The onset age indicated a bimodal distribution: prominent clustering in the first and fourth decades. The infantile-onset group included 12 families, the childhood-onset group consisted of two families and the adult-onset group included nine families. The Charcot-Marie-Tooth Disease Neuropathy Score ranged from 3 to 25 with a mean value of 15.85 ± 5.88. Mutations that changed the cysteine residue (p.Arg98Cys, p.Cys127Trp, p.Ser140Cys and p.Cys127Arg) in the extracellular region were more likely to cause severe early-onset Charcot-Marie-Tooth disease type 1B (CMT1B) or Dejerine-Sottas syndrome. Nonsense-mediated mRNA decay mutations p.Asp35delInsVVYTD, p.Leu174Argfs*66 and p.Leu172Alafs*63 were related to severe infantile-onset CMT1B or Dejerine-Sottas syndrome; however, mutation p.Val232Valfs*19 was associated with a relatively milder childhood-onset CMT1 phenotype. CONCLUSION: Four novel MPZ mutations are reported that expand the genetic spectrum. De novo mutations accounted for 30.4% and were most related to a severe infantile-onset phenotype. Genetic and clinical data from this cohort will provide the baseline data necessary for clinical trials and natural history studies.

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.

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.

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.

Efficacy and safety for robotic bronchoscope in biopsy of pulmonary nodules: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To systematically review the clinical utilization of robotic bronchoscopes in diagnosis of pulmonary nodules, including MonarchTM and IonTM platforms, and then evaluate the efficacy and safety of the procedure. Methods    PubMed, EMbase, Web of Science and Cochrane Central Register of Controlled Trials databases were searched by computer for literature about the biopsy of pulmonary nodules with robotic bronchoscope from January 2018 to February 14, 2022. The quality of research was evaluated with Newcastle-Ottawa Scale. RevMan 5.4 software was used to conduct the meta-analysis. Results    Finally, 19 clinical studies with 1 542 patients and 1 697 targeted pulmonary nodules were included, of which 13 studies used the IonTM platform and 6 studies used the MonarchTM platform. The overall diagnostic rate of the two systems was 84.96% (95%CI 62.00%-95.00%), sensitivity for malignancy was 81.79%(95%CI 43.00%-96.00%), the mean maximum diameter of the nodules was 16.22 mm (95%CI 10.98-21.47), the mean procedure time was 61.86 min (95%CI 46.18-77.54) and the rate of complications occurred was 4.76% (95%CI 2.00%-15.00%). There was no statistical difference in the outcomes between the two systems. Conclusion     Robotic bronchoscope provides a high efficacy and safety in biopsy of pulmonary nodules, and has a broad application prospect for pulmonary nodules diagnosis.

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.