SWI/SNF family mutations in advanced NSCLC: genetic characteristics and immune checkpoint inhibitors' therapeutic implication.

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.

[The ninth edition of TNM staging for lung cancer: precise staging for precise diagnosis and treatment].

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

[Analysis of genomic information and biological characteristics of a bacteriophage against methicillin-resistant Staphylococcus aureus in patients with median sternal incision infection].

Objective: To isolate and purify a bacteriophage against methicillin-resistant Staphylococcus aureus (MRSA), and to analyze its genomic information and biological characteristics. Methods: The experimental research methods were adopted. MRSA (hereinafter referred to as host bacteria) solution was collected from the wound of a 63-year-old female patient with the median sternum incision infection admitted to the Second Affiliated Hospital of Army Medical University (the Third Military Medical University). The bacteriophage, named bacteriophage SAP23 was isolated and purified from the sewage of the Hospital by sewage co-culture method and double-layer agar plate method, and the plaque morphology was observed. The morphology of bacteriophage SAP23 was observed by transmission electron microscope after phosphotungstic acid negative staining. The whole genome of bacteriophage SAP23 was sequenced with NovaSeq PE15 platform after its DNA was prepared by sodium dodecyl sulfonate/protease cleavage scheme, and genomic analysis including sequence assembly, annotation, and phylogenetic tree were completed. The bacteriophage SAP23 solution was co-incubated with the host bacterial solution for 4 h at the multiplicity of infection (MOI) of 10.000 0, 1.000 0, 0.100 0, 0.010 0, 0.001 0, and 0.000 1, respectively, and then the bacteriophage titer was measured by the drip plate method to select the optimal MOI, with here and the following sample numbers of 3. The bacteriophage SAP23 solution was co-incubated with the host bacterial solution at the optimal MOI for 5, 10, and 15 min, respectively, and the bacteriophage titer was measured by the same method as mentioned above to select the optimal adsorption time. After the bacteriophage SAP23 solution was co-incubated with the host bacterial solution at the optimal MOI for the optimal adsorption time, the bacteriophage titers were measured by the same method as mentioned above at 0 (immediately), 5, 10, 15, 20, 30, 40, 50, 60, 80, 100, and 120 min after culture, respectively, and a one-step growth curve was drawn. The bacteriophage SAP23 solution was incubated at 4, 37, 50, 60, 70, and 80 ℃ and pH 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 for 1 h, respectively, to determine its stability. A total of 41 MRSA strains stored in the Department of Microbiology of Army Medical University (the Third Military Medical University) were used to determine the host spectrum of bacteriophage SAP23. Results: The bacteriophage SAP23 could form a transparent plaque on the host bacteria double-layer agar plate. The bacteriophage SAP23 has a polyhedral head with (88±4) nm in diameter and a tail with (279±21) nm in length and (22.6±2.6) nm in width. The bacteriophage SAP23 has a linear, double-stranded DNA with a full length of 151 618 bp and 11 681 bp long terminal repeats sequence in the sequence ends. There were 220 open reading frames predicted and the bacteriophage could encode 4 transfer RNAs, while no resistance genes or virulence factors were found. The annotation function of bacteriophage SAP23 genes could be divided into 5 groups. The GenBank accession number was MZ427930. According to the genomic collinearity analysis, there were 5 local collinear blocks in the whole genome between the bacteriophage SAP23 and the chosen 6 Staphylococcus bacteriophages, while within or outside the local collinear region, there were still some differences. The bacteriophage SAP23 belonged to the Herelleviridae family, Twortvirinae subfamily, and Kayvirus genus. The optimal MOI of bacteriophage SAP23 was 0.010 0, and the optimal adsorption time was 10 min. The bacteriophage SAP23 had a latent period of 20 min, and a growth phase of 80 min. The bacteriophage SAP23 was able to remain stable at the temperature between 4 and 37 ℃ and at the pH values between 4 and 9. The bacteriophage SAP23 could lyse 3 of the 41 tested MRSA strains. Conclusions: The bacteriophage SAP23 is a member of the Herelleviridae family, Twortvirinae subfamily, and Kayvirus genus. The bacteriophage SAP23 has a good tolerance for temperature and acid-base and a short latent period, and can lyse MRSA effectively. The bacteriophage SAP23 is a new type of potent narrow-spectrum bacteriophage without virulence factors and resistance genes.

Knowledge, attitudes and practices on childhood TB among healthcare workers.

BACKGROUND: Increasing childhood TB case detection requires the deployment of diagnostic services at peripheral healthcare level. Capacity and readiness of healthcare workers (HCWs) are key to the delivery of innovative approaches.METHODS: In 2019, HCWs from five district hospitals (DHs) and 20 primary healthcare centres (PHCs) in Cambodia, Cameroon, Cote d´Ivoire, Sierra Leone and Uganda completed a self-administered knowledge-attitudes-practices (KAP) questionnaire on childhood TB. We computed knowledge and attitudes as scores and identified HCW characteristics associated with knowledge scores using linear regression.RESULT: Of 636 eligible HCWs, 497 (78%) participated. Median knowledge scores per country ranged between 7.4 and 12.1 (/18). Median attitude scores ranged between 2.8 and 3.3 (/4). Between 13.3% and 34.4% of HCWs reported diagnosing childhood with (presumptive) TB few times a week. Practising at PHC level, being female, being involved in indirect TB care, having a non-permanent position, having no previous research experience and working in Cambodia, Cameroon, Cote d´Ivoire and Sierra Leone as compared to Uganda were associated with a lower knowledge score.CONCLUSION: HCWs had overall limited knowledge, favourable attitudes and little practice of childhood TB diagnosis. Increasing HCW awareness, capacity and skills, and improving access to effective diagnosis are urgently needed.

[A short half-life of cccDNA offer or ignite hope for hepatitis B cure under nucleos(t)ide analogues treatment].

Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the template for HBV replication. Currently, there is a lack of therapeutic drugs that directly target cccDNA. Therefore, blocking cccDNA supplements as fast as possible and reducing the existing cccDNA is the key to achieving a complete cure of chronic hepatitis B. Previous studies have suggested that cccDNA had a long half-life, but a recent study showed that it only took a few months to update cycle of cccDNA pool, and its number was much less than previously predicted. In the future, with the advent of new antiviral drugs that can completely inhibit HBV replication, it is expected that the cccDNA pool will be completely cleared due to its supplement complete blockade, so as to achieve virological cure of chronic hepatitis B.

[Preliminary results of Chinese magnetic sphincter augmentation in treating gastroesophageal reflux disease].

Objective: To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD). Methods: According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results: A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months (M(Q(R))). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery(n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions: SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.

[Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia].

Objective: To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP). Methods: The correlation between ALT, AST and other liver enzyme changes condition and NCP patients' disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy. t-test or Spearman rank correlation analysis was used for statistical analysis. Results: ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was only expressed in bile duct epithelial cells of normal liver tissues, and very low in hepatocytes. In a mouse model of acute liver injury with partial hepatectomy, Ace2 expression was down-regulated on the first day, but it was elevated up to twice of the normal level on the third day, and returned to normal level on seventh day when the liver recovered and hepatocyte proliferation stopped. Whether this phenomenon suggests that the bile duct epithelial cells with positive expression of Ace2 participate in the process of liver regeneration after partial hepatectomy deserves further study. In RNA-Seq data, 77 transcription factors were positively correlated with the expression of Ace2 (r > 0.2, FDR < 0.05), which were mainly enriched in the development, differentiation, morphogenesis and cell proliferation of glandular epithelial cells. Conclusion: We assumed that in addition to the over activated inflammatory response in patients with NCP, the up-regulation of ACE2 expression in liver tissue caused by compensatory proliferation of hepatocytes derived from bile duct epithelial cells may also be the possible mechanism of liver tissue injury caused by 2019 novel coronavirus infection.

Classification of water contamination developed by 2-D Gabor wavelet analysis and support vector machine based on fluorescence spectroscopy.

The identification of the specific categories of pollutants in the urban water supply system is necessary. Traditional detection methods are based mainly on common water quality indicators. However, inspecting these water quality indicators is made difficult by issues such as long analysis time, insufficient sensitivity, need for reagents, and generation of waste liquid. These problems hinder high-frequency water detection and monitoring. In this study, three-dimensional (3D) fluorescence spectroscopy is adopted as a monitoring method for water quality. An identification method based on two-dimensional (2D) Gabor wavelets and support vector machine (SVM) multi-classification is also proposed. The Delaunay triangulation method for interpolation is used to pre-process 3D fluorescence spectra and thereby eliminate Rayleigh scattering and Raman scattering. A 2D Gabor wavelet function generated by filters of different scales and rotation angles is proposed to extract the features of the spectra. The block statistics method, based on Gabor feature description, is employed to enhance the efficiency in describing spectra features. Then, multiple SVM classifiers are used in pollutant classification and recognition. By comparing the proposed method with principal component analysis, which is a commonly used feature extraction method, this study finds that the application of 2D Gabor wavelets and block statistics can effectively describe the characteristics of 3D fluorescence spectra. Moreover, 2D Gabor wavelets achieve high classification accuracy, especially for substances with closely positioned or overlapping characteristic peaks.

[Analysis the features of familial benign paroxysmal positional vertigo].

Objective:The family heredity of BPPV disease was preliminarily discussed in order to guide the clinical practice, prevent early and shorten the course of BPPV disease in the future. Method:Familial BPPV patients were enquired and registered in detail, including gender, age at first onset, occupation, inducing factors, symptoms, diagnosis, sleep status and clinical manifestations. Analysis of the clinical data. Result:Nine patients with idiopathic BPPV from four families had no definite pathogenic factors, accounting for 0.4% of the patients with idiopathic BPPV, including 3 males and 6 females; the age of first onset ranged from 31 to 66 years old. the course of disease ranged from 2 days to 8 years; the duration of nystagmus ranged from seconds to 1 minute. The main clinical symptoms were dizziness and visual rotation related to position transformation. Family 1, 3 and 4 patients had a history of fatigue. Family 2 patients had a predisposing factor of forced lateral decubitus due to lumbar discomfort. All patients had nystagmus lasting less than 1 minute and were single-tube involvement, all patients were canalithiasis. Different patients in the same family have different pathogenic locations. Conclusion:Familial BPPV is urgent to attract the attention of clinicians and the public. Early clinical test for suspected familial BPPV can play a role in early prevention and shorten the process of disease, so as to improve the life quality of patients.

[Experiences of esophageal replacement with ileocolon graft: a series of 34 cases].

Objective: To evaluate the safety and effectiveness of esophageal replacement with ileocolon graft. Methods: Totally 34 cases of esophageal replacement with ileocolon graft from July 2015 to November 2017 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University were analyzed retrospectively, including 24 male and 10 female, aging from 7 to 72 years old. Esophageal replacement with ileocolon graft by right and/or middle colic artery as a blood supply using retrosternal route except one subcutaneous route. The primary esophageal disease, postoperative complication rate and quality of life were analyzed. Results: The overall postoperative complication rate was 23.5% (8/34), cervical anastomotic leakage rate of 5.9% (2/34), necrosis of colon graft of 5.9% (2/34). There were 3 patients experienced re-operation including 2 patients with colon graft necrosis and 1 patient with intestinal obstruction after ERC. One patient with colon graft necrosis died of septic shock after reoperation. Six cases of cervical esophago-jejunal anastomosis stenosis and 1 case of diarrhea occurred in the later time. All patients were followed up for a median time of 9 months (range: 1 to 28 months), 32 cases survived but 1 patient died until last follow-up by the end of December 2017. Conclusion: Esophageal replacement with ileocolon graft by right and/or middle colic artery as a blood supply using retrosternal route was safe and effective.

Experimental study on TGF-ß1-mediated CD147 expression in oral submucous fibrosis.

OBJECTIVE: Although previous evidence indicates that CD147 is closely involved in the progression of organ fibrosis and various signaling pathways have been proven to regulate its expression, the role of CD147 in oral submucous fibrosis (OSF) remains largely unknown. METHODS: In this study, we investigated the expression of CD147 and transforming growth factor ß1 (TGF-ß1) in human samples of an OSF tissue array by immunohistopathology. Pearson's correlation analysis was conducted to explore the correlation between CD147 and TGF-ß1. Immunofluorescence and Western blotting were used to investigate to levels of CD147 in Human Oral Keratinocytes (HOKs) followed by TGF-ß1 or LY2157299, an inhibitor of TGF-ß1 receptor and arecoline stimulation. RESULTS: We found that CD147 was highly expressed in both HOKs and the fibrotic oral mucosa and that this expression was correlated with TGF-ß1 expression. Additionally, CD147 levels were significantly associated with the fibrosis stage. The TGF-ß1 signaling pathway was found to be mainly responsible for CD147 up-regulation after arecoline treatment whereas inhibition of TGF-ß1 down-regulated CD147 expression. CONCLUSION: Our findings suggest arecoline promotes CD147 expression via the TGF-ß1 signaling pathway in HOKs, whereas overexpression of CD147 may promote OSF progression.

Targeting the CXCR4/CXCL12 axis in treating epithelial ovarian cancer.

Ovarian carcinoma is the most crucial and difficult target for available therapeutic treatments among gynecological malignancies, and great efforts are required to find an effective solution. Molecular studies showed that the chemokine stromal cell-derived factor-1 (also known as CXCL12) and its receptor, CXCR4, are key determinants of tumor initiation, progression and metastasis in ovarian carcinomas. Hence, it is generally believed that blocking the CXCR4/CXCL12 pathway could serve as a potential therapy for patients with ovarian cancer. Herein, we investigated the role of the CXCR4/CXCL12 axis in regulating ovarian cancer progression. Using flow cytometry, a real-time PCR and western blot analyses, we showed that the chemokine receptor CXCR4 protein and mRNA were overexpressed in human epithelial ovarian cancer cell lines, and these were closely correlated with poor outcomes. Moreover, silencing CXCR4 by small hairpin RNA in HTB75 cells reduced cell proliferation, migration and invasion and significantly reduced RhoA and Rac-1/Cdc42 expressions, whereas overexpression of CXCR4 in SKOV3 cells significantly increased cell migration and markedly increased RhoA, Rac-1/Cdc42 levels. Silencing CXCR4 also led to decreased in vitro cytotoxicity of AMD3100, a specific antagonist of CXCR4, which exerts its effect upon CXCR4 expression. Remarkably, knockdown of CXCR4 in HTB75 cells led to a significantly decreased capability to form tumors in vivo, and the Ki67 proliferation index of xenograft tumors showed a dramatic reduction. Our results revealed that the CXCR4/CXCL12 pathway represents a promising therapeutic target for epithelial ovarian carcinoma.

[Expression and significance of tumor necrosis factor alpha, matrix metalloproteinase 2 and collagen in skin tissue of pressure ulcer of rats].

OBJECTIVE: To observe the expressions of tumor necrosis factor alpha (TNF-α), matrix metalloproteinase 2 (MMP-2) and collagen in local skin tissue of pressure ulcer of rats, and to explore the possible mechanism of the pathogenesis of pressure ulcer. METHODS: Forty male SD rats were divided into normal control group, 3 d compression group, 5 d compression group, 7 d compression group, and 9 d compression group according to the random number table, with 8 rats in each group. The rats in normal control group did not receive any treatment, whereas the rats in the latter 4 groups were established the deep tissue injury model (3 d compression group) and pressure ulcer model (the other 3 groups) on the gracilis muscle on both hind limbs using a way of cycle compression of ischemia-reperfusion magnet. The rats in 3 d compression group received only three cycles of compression, while the compressed skin of the rats in 5 d compression group, 7 d compression group, and 9 d compression group were cut through and received pressure to 5, 7 and 9 cycles after three cycles of compression, respectively. The rats in 3 d compression group were sacrificed immediately after receiving compression for 3 d (the rats in normal control group were sacrificed at the same time), and the rats in the other 3 groups were respectively sacrificed after receiving compression for 5, 7, and 9 d, and the skin tissue on the central part of gracilis muscle on both hind limbs were harvested. The morphology of the skin tissue was observed with HE staining. The expression of collagen fiber was observed with Masson staining. The expressions of collagen type Ⅳ and MMP-2 were detected by immunohistochemical method. The expressions of TNF-α and phosphorylated NF kappa B (NF-κB) were determined by Western blotting. Data were processed with one-way analysis of variance and LSD test. RESULTS: (1) In normal control group, the skin tissue of rats was stratified squamous epithelium, with the clear skin structure, and there was no obvious infiltration of inflammatory cells. In 3 d compression group, the skin layers of rats were clear, with quite a few fibroblasts, and the inflammatory cells began to infiltrate. In 5 d compression group, 7 d compression group, and 9 d compression group, the epidermis of rats thickened, with the number of fibroblasts reduced, and the infiltration of inflammatory cells enhanced with the compressed time prolonging. (2) In normal control group, the collagen fibers in skin tissue of rats were arranged in order, with rich content. In 3 d compression group, the collagen fibers in skin tissue of rats were arranged orderly, with high expression level, which was similar to that in normal control group (P>0.05). In 5 d compression group and 7 d compression group, the collagen fibers in skin tissue of rats were arranged in disorder, with the expression level gradually reduced, which were significantly lower than that in normal control group (with P values below 0.01). In 9 d compression group, the expression of collagen fiber in skin tissue of rats was a little higher than that in 7 d compression group, but it was still significantly lower than that in normal control group (P<0.01). (3) The expressions of collagen type Ⅳ in skin tissue of rats in normal control group, 3 d compression group, 5 d compression group, 7 d compression group, and 9 d compression group were respectively 11.0±2.8, 9.0±1.7, 8.3±2.8, 5.1±1.8, and 5.4±1.2. The expression of collagen type Ⅳ in skin tissue of rats in 3 d compression group was similar to that in normal control group (P>0.05). The expressions of collagen type Ⅳ in skin tissue of rats in 5 d compression group, 7 d compression group, and 9 d compression group were significantly lower than that in normal control group (P<0.05 or P<0.01). The expression of MMP-2 in skin tissue of rats in 3 d compression group was similar to that in normal control group (P>0.05). The expressions of MMP-2 in skin tissue of rats in 5 d compression group, 7 d compression group, and 9 d compression group were significantly higher than that in normal control group (P<0.05 or P<0.01). (4) The expression of TNF-α in skin tissue of rats in normal control group was 0.48±0.11, and the expressions of TNF-α in skin tissue of rats in 3 d compression group, 5 d compression group, 7 d compression group, and 9 d compression group were respectively 0.84±0.08, 1.13±0.19, 1.34±0.16, and 1.52±0.23, which were all significantly higher than that in normal control group (with P values below 0.01). The expressions of phosphorylated NF-κB in skin tissue of rats in 3 d compression group and 9 d compression group were similar to that in normal control group (with P values above 0.05), and the expressions of phosphorylated NF-κB in skin tissue of rats in 5 d compression group and 7 d compression group were significantly higher than that in normal control group (P<0.05 or P<0.01). CONCLUSIONS: The high expression of MMP-2 and reduction of collagen induced by inflammatory reaction mediated by the high expression of TNF-α in local skin tissue of pressure ulcer of rats may be one of the important reasons for the formation of pressure ulcer.

Anti-CII antibody as a novel indicator to assess disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects a variety of organ systems. Anti-dsDNA Abs and complement factors have been used as indicators of lupus activity for more than 50 years. A novel indicator of activation in SLE is reported in this paper. Anti-collagen type II (CII) Ab was obviously elevated in patients with SLE compared to those patients with ankylosing spondylitis (AS) and healthy controls (HCs). Anti-CII-Ab-positive patients with SLE showed significantly higher levels of serum IgG and higher titers of ANA but lower levels of C3 and C4 than controls. A positive correlation was demonstrated between anti-CII Ab and serum IgG in SLE patients (r = 0.50, p < 0.0001). The negative correlations of anti-CII Ab with C3 and C4 were observed in SLE patients (r = -0.36, p = 0.0013; r = -0.37, p = 0.0006, respectively). The reduced anti-CII Ab level was accompanied by decreased level of serum IgG and increased levels of C3 and C4 after regular treatment. Therefore, anti-CII Ab could be a novel indicator for monitoring activity of SLE.

Changes and clinical significance of peripheral blood helper T lymphocyte and natural killer (NK) cells in unexplained recurrent spontaneous abortion (URSA) patients after abortion and successful pregnancy .

OBJECTIVE: This study aims to investigate the number changes and the clinical significance of the peripheral blood T lymphocyte subsets and NK (natural killer) cells in unexplained recurrent spontaneous abortion (URSA) patients before and after abortion, as well as after successful pregnancy. MATERIALS AND METHODS: Thirty-nine URSA patients (URSA-abortion group), among who 22 patients were followed up until the final successful parturition (URSA-pregnancy group), 31 normal-pregnancy (NP) cases and 25 normal non-pregnancy (NNP) control cases in which the peripheral blood T lymphocytes and subsets, B cells, and NK cells were assessed flow cytometry. RESULTS: Compared with the URSA-pregnancy group and the NP group, the Th cells and NK cells of the URSA-abortion group increased (p < 0.05); compared with the NNP group, the total number of T cells decreased after the first, second, and third month of the URSA abortion (p < 0.05); Th cells decreased within one to six months of the URSA abortion (p < 0.05); proportion of NK cells was significantly higher in URSA patients (p < 0.05). CONCLUSION: The abnormal numbers of the peripheral blood T cell subsets and NK cells were related with the occurrence of URSA.

Comparative study of functional and aesthetically outcomes of reverse digital artery and reverse dorsal homodigital island flaps for fingertip repair.

UNLABELLED: This retrospective study was designed to compare functional and cosmetic outcomes of the reverse digital artery island flap and reverse dorsal homodigital island flap in fingertip repair. A total of 23 patients were followed for 24 to 30 months. The reverse digital artery island flap was used in 12 patients, and reverse dorsal homodigital island flap in another 11 patients. Flap sensibility was assessed using the Semmes-Weinstein monofilament test and static 2-point discrimination test. Patient satisfaction, active motion of the finger joints, complications and cold intolerance were evaluated. The static 2-point discrimination and Michigan Hand Outcomes Questionnaire (appearance) of the fingers treated with a reverse digital artery flap were significantly better than those with a reverse dorsal homodigital flap. The static 2-point discrimination of the skin-grafted donor sides after dorsal homodigital flap were poorer than that in the contralateral finger. No significant differences were found between the two flaps for pressure or touch sensibility, active ranges of digital motion, complications and cold intolerance. LEVEL OF EVIDENCE: III.

Dental Abnormalities Caused by Novel Compound Heterozygous CTSK Mutations.

Cathepsin K (CTSK) is an important protease responsible for degrading type I collagen, osteopontin, and other bone matrix proteins. The mutations in the CTSK gene can cause pycnodysostosis (OMIM 265800), a rare autosomal recessive bone dysplasia. Patients with pycnodysostosis have been reported to present specific dental abnormalities; however, whether these dental abnormalities are related to dysfunctional CTSK has never been reported. Here we investigated the histologic changes of cementum and alveolar bone in a pycnodysostosis patient, caused by novel compound heterozygous mutations in the CTSK gene (c.87 G>A p.W29X and c.848 A>G p.Y283C). The most impressive manifestations in tooth were extensive periradicular high-density clumps with unclear periodontal space by orthopantomography examination and micro-computed tomography scanning analysis. Hematoxylin/eosin and toluidine blue staining and atomic force microscopy analysis showed that the cementum became significantly thickened, softened, and full of cementocytes. The disorganized bone structure was the main character of alveolar bone. The p.W29X mutation may represent the loss-of-function allele with an earlier termination codon in the precursor CTSK polypeptide. Residue Y283 is highly conserved among papain-like cysteine proteases. Three-dimensional structure modeling analysis found that the loss of the hydroxybenzene residue in the Y283C mutation would interrupt the hydrogen network and possibly affect the self-cleavage of the CTSK enzyme. Furthermore, p.Y283C mutation did not affect the mRNA and protein levels of overexpressed CTSK in COS-7 system but did reduce CTSK enzyme activity. In conclusion, the histologic and ultrastructural changes of cementum and alveolar bone might be affected by CTSK mutation via reduction of its enzyme activity (clinical trial registration: ChiCTR-TNC-10000876).

Cost-effectiveness of a tuberculosis active case finding program targeting household and neighborhood contacts in Cambodia.

In many high-risk populations, access to tuberculosis (TB) diagnosis and treatment is limited and pockets of high prevalence persist. We estimated the cost-effectiveness of an extensive active case finding program in areas of Cambodia where TB notifications and household poverty rates are highest and access to care is restricted. Thirty operational health districts with high TB incidence and household poverty were randomized into intervention and control groups. In intervention operational health districts, all household and symptomatic neighborhood contacts of registered TB patients of the past two years were encouraged to attend screening at mobile centers. In control districts, routine passive case finding activities continued. The program screened more than 35,000 household and neighborhood contacts and identified 810 bacteriologically confirmed cases. The cost-effectiveness analysis estimated that in these cases the reduction in mortality from 14% to 2% would result in a cost per daily adjusted life year averted of $330, suggesting that active case finding was highly cost-effective.

Immune monitoring in kidney transplant recipients could predict acute rejection by a new method: flow cytometric microcarrier assay.

BACKGROUND: Peripheral blood lymphocytes (PBL) of kidney transplant recipients stimulated in vitro release tumor necrosis factor (TNF)-α and interferon (IFN)-γ into the supernate as detected by a flow cytometric microcarrier assay (FCMA) that we used to predict acute rejection episodes. METHODS: Fifty-two kidney transplant recipients were divided into 2 groups; stable function (STA; n = 30) and acute rejection (ARG; n = 22) for comparison with healthy volunteers (n = 10). PBL were stimulated for 8 hours with phorbol myphnistate acetate and ionomycin, thereafter detecting TNF-α and IFN-γ in culture supernates by FCMA. Receiver operating characteristics (ROC) procedures were used to assess the sensitivity and specificity to predict acute rejection. RESULTS: The fluorescence intensity of TNF-α and IFN-γ in culture supernates was significant higher among healthy controls than STA: 68.38 ± 28.59 vs 51.08 ± 34.05, respectively (P < .05). The intensity of TNF-α and IFN-γ in ARG (144.47 ± 81.21 and 116.61 ± 53.89, respectively) was significant higher than STA (P < .001). The sensitivity and specificity to predict acute rejection were 86.4% and 86.7%, respectively, when analyzed by ROC curves combining TNF-α and IFN-γ. The intensity in noncultured plasma from ARG or STA was significant lower than that in culture supernates from ARG and STA with sensitivity and specificity to predict acute rejection episodes of 63.6% and 73.3%, respectively, when combining TNF-α and IFN-γ. CONCLUSIONS: Monitoring the expression of TNF-α and IFN-γ in cell culture supernates after stimulation of kidney transplant recipient PBL in vitro using FCMA predicted acute rejection episodes.