[Progress in novel biomarkers of anti-tuberculosis drug-induced liver injury].

Anti-tuberculosis drug-induced liver injury(ATB-DILI) is the most common adverse reaction during anti-tuberculosis therapy in tuberculosis patients. At present, the diagnosis of ATB-DILI is mainly based on traditional biomarkers such as transaminases, but these indicators have low specificity for liver toxicity, they cannot explain the mechanism of liver injury and the early onset of ATB-DILI. Based on the prediction of disease severity, treatment and prevention, this paper described the current potential biomarkers of ATB-DILI.

[Survival and prognosis analysis of patients with Hodgkin lymphoma treated with standard treatment paradigm].

Objective: To analyze the survival and prognosis of Hodgkin lymphoma (HL) patients receiving standard first-line therapy. Methods: Data of clinical characteristics and treatment outcomes of patients with HL diagnosed in Cancer Hospital Chinese Academy of Medical Sciences (CHCAMS) from January 1st, 2000 to December 31st, 2018 who received standard first-line treatment were retrospectively analyzed and compared with that of HL patients who received treatment in the Surveillance, Epidemiology and End Results (SEER) database in the United States during the same period. Factors associated with freedom from progression (FFP) of patients in CHCAMS were analyzed. Treatment and survival data of patients with relapsed/refractory HL (r/rHL) who had failed the standard first-line treatment during the corresponding period in CHCAMS were collected to analyze the outcomes of salvage therapy. Results: A total of 764 HL patients in CHCAMS were included in this study. The median age was 30 years (range, 14-83 years), with 424 males and 340 females. By February 26th, 2022, the patients were followed-up for a median time of 111 months(range, 0.3-262.0 months). Lymphoma-specific survival (LSS) rate and overall survival (OS) rate at 10 years for HL patients in CHCAMS was 91.7% (95%CI: 89.5%-93.9%) and 87.1% (95%CI: 84.5%-89.8%), respectively. LSS and OS rate at 10 years for HL patients from SEER database was 86.8% (95%CI: 86.3%-87.2%) and 79.0% (95%CI: 78.5%-79.5%), respectively. The unadjusted LSS and OS rate for patients in CHCAMS were higher than those for patients from SEER database (both P<0.001). No significant difference was observed in LSS and OS rate (both P>0.05) between the two groups after adjustment. European Organization for Research and Treatment of Cancer staging system (early-stage unfavorable: HR=2.35, 95%CI: 1.13-4.89, P=0.023; advanced stage: HR=5.44, 95%CI: 2.62-11.30, P<0.001) and serum ß2 microglobulin (HR=1.67, 95%CI: 1.08-2.58, P=0.021) were influencing factors of FFP for patients in CHCAMS. The complete remission rate, median progression-free survival (PFS), 5-year PFS rate and 5-year OS rate for the 116 patients with r/rHL was 37.9% (95%CI: 29.6%-47.0%), 15.0 months (95%CI: 9.9-20.1 months), 29.9% (95%CI: 20.9%-38.9%) and 62.9% (95%CI: 54.1%-71.7%), respectively. Conclusions: The outcomes of HL patients receiving standard first-line treatment are excellent. However, the therapeutic effect of HL patients who incurrs disease progression or relapse after standard first-line treatment is not satisfying.

[Advances in the research of centration in small incision lenticule extraction].

Small incision lenticule extraction (SMILE) is a new technique that exhibits excellent efficacy, safety and predictability for the correction of myopia and myopic astigmatism. However, one potential limitation of this technique is that the centration during femtosecond laser cutting might be subject to the surgeon's experience and patient's cooperation. To achieve accurate centration in SMILE is the key to obtaining good postoperative visual outcomes. This review summarizes relevant research results and discusses the centration methods and the influencing factors in SMILE, so as to provide reference for clinical practice of SMILE.

Multiple b-value diffusion-weighted imaging in differentiating benign from malignant breast lesions: comparison of conventional mono-, bi- and stretched exponential models.

AIM: To prospectively evaluate multiple b-value diffusion-weighted imaging (DWI) in differentiating malignant from benign breast lesions. MATERIALS AND METHODS: The study cohort included 103 patients who underwent 3 T magnetic resonance imaging (MRI). The conventional sequences included T1-weighted dynamic contrast-enhanced, T1-weighted and T2-weighted fat-suppressed sequences, single b-value (b=0, 1000 s/mm2) DWI, and multiple b-values (12 values, from 0 to 3,000 s/mm2) DWI. Pathological diagnosis of breast lesions was based on the latest World Health Organization (WHO) guide on the pathology and immunohistochemistry of the breast. SPSS Statistics V19.0 was used for the statistics analysis. RESULTS: The following parameters were calculated: apparent diffusion coefficient (ADC), tissue diffusivity (D), perfusion fraction (f), pseudo-diffusion coefficient (D∗), distributed diffusion coefficient (DDC), and alpha (α) by the same radiologist twice (interval time of 3 months). There was good inter/intra-observer agreement for each of the parameters. The D, D∗, f, DDC, and α values were significantly different among malignant tumours, benign lesions, and normal breast tissue (p<0.05). CONCLUSION: D, f, DDC, α, and ADC values have good sensitivity and specificity, respectively. In addition, the combined use of D and f or DDC and α has good diagnostic performance. Thus, the applications of the new multi-b DWI variables or combined variables are promising.

Performance of InGaN based green laser diodes improved by using an asymmetric InGaN/InGaN multi-quantum well active region.

Series of green laser diodes (LDs) with different (In)GaN barrier layers are investigated. It is found that the optical confinement factor of multi-quantum well (MQW) always increases with increasing indium content of InGaN barrier layer, which results in a decrease of threshold current when indium content of InGaN barrier layer increases from 0 to 5%. However, when a high In content InGaN barrier is used (> 5%), both threshold current and slop efficiency of LDs deteriorate. It may be attributed to the waste of carriers in the potential well at the interface between the last barrier (LB) and the upper waveguide (UWG) layers, which is induced by the piezoelectric polarization effect in high In content InGaN LB layer. Therefore, a new LD structure using a thin thickness of the LB layer to reduce the effect of polarization shows a low threshold current and a high output power even when the In content of barrier layers is as large as 7%.

Evolution of differential efficiency in blue InGaN laser diodes before and after a lasing threshold.

The optical power emitting from the cavity facet of blue InGaN-based laser diodes (LDs) is measured to investigate the efficiency droop. The efficiency droop behavior of blue InGaN-based LDs near the threshold is confirmed in our experiments. From measurements of optical power at different wavelengths, it is analyzed that the droop behavior of LDs can be ascribed to the efficiency reduction of longer wavelengths. The efficiency of longer wavelengths is subject to the carrier occupation process in quantum levels. In addition, it is found that the droop behavior may be largely affected by the relatively large threshold current of InGaN-based LDs and the screening effect of polarization, and it can be suppressed by stimulated emission.

Role and diagnostic value of gene variants in assessing the risk of chronic obstructive pulmonary disease.

Meta-analyses have revealed many positive associations between gene variants and susceptibility to chronic obstructive pulmonary disease (COPD). However, some of those positive results may be false positives. Therefore, we investigated the genetic polymorphisms associated with COPD risk and determined their diagnostic value. We extracted the odds ratio (OR) and 95% confidence interval for each polymorphism from published meta-analyses concerning gene variants and COPD susceptibility in October 2014, subsequently we calculated false-positive report probabilities (FPRPs) for statistically significant associations (P value < 0.05). We determined the diagnostic value of the true positive polymorphisms of COPD using the Meta-DiSc software. Twenty-five gene polymorphisms were significantly associated with COPD risk. The FPRP test results were as follows: 1) when the prior probability was 0.001 and the OR was 1.5, ADAM33 rs612709, CHRNA3/5 rs1051730, CHRNA3/5 rs8034191, CHRNA3/5 rs16969968, and TGFB1 rs1800470 were truly associated with COPD risk (FPRP < 0.2); 2) when the prior probability was 0.000001 and the OR was 1.5, all the variants except TGFB1 rs1800470 remained noteworthy; and 3) when the probability was 0.000001 and the OR was 1.2, ADAM33 rs612709 and CHRNA3/5 rs1051730 remained true positives. Unfortunately, the results of the diagnostic accuracy meta-analyses suggested that none of the variants had high value for COPD diagnosis.

Biochemical properties of the recurrent LMX1b truncated mutant carried in a Taiwanese family with nail-patella syndrome.

BACKGROUND: Loss of the DNA-binding activity of a transcription factor is detrimental to its function in responsive gene regulation. We diagnosed a Taiwanese family with nail-patella syndrome (NPS) whose members inherited the mutated LMX1b transcription factor with no DNA-binding homeodomain. The loss-of-function variants cause haploinsufficiency of LMX1b, leading to the clinical manifestation of NPS. The underlying molecular mechanism is unclear. OBJECTIVES: To test whether the recurrent pathogenic truncated LMX1b-R198X reported in our patients might be a functional protein. Its biochemical properties were explored. METHODS: The luciferase reporter driven by the human interleukin (IL)-6 gene promoter was assayed to measure the transcriptional activity of LMX1b. The nuclear localization of different enhanced green fluorescent protein-tagged LMX1b proteins was observed using fluorescence microscopy. Western blotting was employed to evaluate the expression of various transfected LMX1b constructs. RESULTS: LMX1b-R198X enhanced the IL-6 promoter activity activated by the wild-type LMX1b and diminished the promoter activity induced by phorbol 12-myristate 13-acetate. LMX1b-R198X carried out its effect differentially in the expression of various human genes. The nuclear localization of the wild-type LMX1b was disrupted by the C-terminus truncation. The protein stability exhibited by LMX1b-R198X appears to be much higher than that of the wild-type protein. CONCLUSIONS: We demonstrated that loss of function might not be the only way for mutated LMX1b to cause haploinsufficiency as the main pathogenic mechanism for NPS. LMX1b-R198X has less nuclear localization and higher stability than the wild-type protein; consequently, it might function as a competitor to sequester other effectors by protein-protein interaction to interfere with downstream transcriptional events.

Dietary Supplementation of Magnesium Sulfate during Late Gestation and Lactation Affects the Milk Composition and Immunoglobulin Levels in Sows.

This experiment was conducted to investigate the effects of dietary supplementation of magnesium sulfate (MgSO4) during late gestation and lactation on sow and litter performance, fecal moisture, blood biochemistry parameters, immunoglobulin levels and milk composition in sows. Forty-eight sows (Yorkshire×Landrace, 4th to 5th parity) were randomly allocated to 1 of 4 dietary treatments supplemented with 0, 200, 400, or 600 mg/kg MgSO4 (n = 12). The experiment started on day 90 of gestation and continued through day 21 of lactation. Blood samples were collected on day 107 of gestation, day 0 (farrowing) and 21 (weaning) of lactation for the analyses of the blood biochemistry parameters and immunoglobulin levels. The colostrum and milk samples were obtained on day 0 and 14 of lactation, respectively. Fecal samples were collected from the sows on day 107 of gestation as well as day 7 and 20 of lactation to determine fecal moisture content. The results showed that the survival percentage of piglets and the litter weight at weaning were decreased linearly (p<0.05) and other parameters of the sow or litter performance were not influenced (p>0.05) by MgSO4 supplementation. The fecal moisture content of the sows were increased (p<0.05) linearly as dietary MgSO4 increased on day 7 and 20 of lactation. Supplementation with MgSO4 increased the plasma magnesium (Mg) level linearly (p<0.05) and had a trend to increase total protein level (p>0.05 and p<0.10). However, an increase in the dietary MgSO4 level resulted in a linear decrease in the colostrum fat content (p<0.05). Dietary MgSO4 supplementation enhanced the immunoglobulin G (IgG) level (linear, p<0.05) in plasma on day of farrowing and immunoglobulin A (IgA) level in colostrum (quadratic, p<0.05) and milk (linear, p<0.05) of the sows. These results indicated that supplementation with MgSO4 during late gestation and lactation may have the potential to prevent sow constipation, but may also result in some negative effects.

A systematic insight into a single-stage deammonification process operated in granular sludge reactor with high-loaded reject-water: characterization and quantification of microbiological community.

AIMS: Reject-water from sludge dewatering was treated in a single-stage deammonification reactor. The aims were to characterize the microbiological community within deammonification granules. METHODS AND RESULTS: In situ mapping of the intact granular sludge were made with fluorescent in situ hybridization (FISH). The Planctomycetes community in the destroyed granular sludge was characterized by FISH, polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), cloning and sequence analysis. CONCLUSIONS: AOB within Betaproteobacteria were concentrated within the first 50-100 µm of the granule, and Planctomycetes in the first 100-200 µm were responsible for nitrogen elimination. PCR-DGGE verified the higher diversity of Planctomycetes in the deammonification reactor than the anaerobic cultivation. The sequence analysis after PCR-DGGE and cloning identified the dominant Planctomycetes species for anammox reaction as Ca. Brocadia fulgida (accession no. EU478693). FISH detection using the universal probe AMX368 specific for all anammox bacteria including Ca. Brocadia fulgida failed; however, the probe BFU613 specific for Ca. Brocadia fulgida gave clear positive FISH signals. The three-dimensional structure of the ribosome may hinder binding of the universal probe to the corresponding 16S rRNA region. SIGNIFICANCE AND IMPACT OF THE STUDY: A combination of multiple methods for the analysis of the microbiological community was necessary. Oligonucleotide probes should be carefully selected, and a negative FISH analysis has to be verified by other molecular biological techniques.

[Clinical analysis of 10 cases with extramedullary plasmacytoma of the head and neck].

Objective: To explore the clinical characteristics, treatment methods and outcomes of extramedullary plasmacytoma of the head and neck. Methods: A retrospective analysis was conducted on 10 cases with extramedullary plasmacytoma of the head and neck who were admitted to Henan Tumor Hospital from January 2005 to January 2020. Among the 10 patients, 6 were male and 4 were female. The average age at diagnosis was 56.3 years old (34-74 years old). Among them, 3 cases were located in the nasal cavity, 2 cases in the nasopharynx, 1 case in the sinuses, 2 cases in the larynx, 1 case in the oropharynx, and 1 case in the cervical lymph nodes. Treatments were administered according to tumor size and resection extent. Complete surgical excision (negative margins) was preferred, followed by adjuvant radiotherapy or radiotherapy alone. The clinical characteristics, diagnosis, treatment and prognosis of EMP were analyzed. Results: The patients' symptoms were not specific, frequently with local obstruction symptom and localized masses. All patients were confirmed pathologically as suffering from monoclonal plasmacytoma, with negative bone marrow biopsy and negative skeletal survey. Five patients received surgery, 3 received radiotherapy, and 2 received surgery with additional radiation. The follow-up time was 16-125 months, with a median of 92 months. Two patients developed into multiple myeloma. One patient who received radiotherapy after surgery relapsed after 7 years of follow-up and again received surgical treatment, with no evidence of second recurrence. The remaining patients had no recurrence or progression. Conclusion: Extramedullary plasmacytoma of the head and neck has a good prognosis. Surgical treatment can be considered for completely resectable lesions.

[DNA double-strand breaks repair capacity and risk of differentiated thyroid cancer: a case-control study].

Objective: To study the influencing factors of DNA double-strand breaks (DSB) repair capacity and relationship with differentiated thyroid cancer (DTC). Methods: A total of 140 patients with thyroid diseases admitted to the Henan Cancer Hospital from January 2020 to March 2020 were retrospectively analyzed, including 26 males and 114 females, aged from 18 to 78 years old. According to the pathological results, the patients were divided into DTC group (90 cases) and control group or benign thyroid nodules (BTN) group (50 cases). The DSB repair ability of peripheral blood T lymphocytes was measured by flow cytometry. The data of two groups were compared by Wilcoxon rank sum test to evaluate the relationship between DSB repair ability and the risk of DTC. According to the median repair ability of DSB in BTN group, the repair ability of DSB was divided into high and low categories, and the factors influencing the repair ability of DSB were analyzed by Logistic regression method. SPSS 22.0 software was used to analyze the data. Results: The DSB repair capacity was 27.87% in DTC group and 36.75% in BTN group, with significant difference (Z=-3.999,P<0.05). Logistic regression analysis suggested that patients with thyroid cancer had lower DSB repair capacity than patients without cancer (OR=2.245; 95%CI: 1.067-4.725; P=0.033), and patients with a history of radiation exposure had a reduced DSB repair capacity (OR=2.698; 95%CI: 1.271-5.725, P=0.010). Conclusion: The risk of DTC increases in patients with low DSB repair capacity. Radiation exposure is a risk factor for the reduction of DSB repair capacity.

MiR-34a affects G2 arrest in prostate cancer PC3 cells via Wnt pathway and inhibits cell growth and migration.

OBJECTIVE: To investigate the effect and mechanism of miRNA-34a overexpression on proliferation and migration of PC3 prostate cancer cells. PATIENTS AND METHODS: Benign prostatic hyperplasia tissue (30 cases), prostate cancer tissue (30 cases), and prostate paracancerous tissue (30 cases) were collected. Levels of miRNA-34a in these fresh tissues were measured by fluorescence quantitative PCR. PC3 cells were divided into non-loaded group and overexpression group. Cells in the non-loaded group were transfected with non-loaded plasmid. Cells in the overexpression group were transfected with miRNA-34a plasmid, and the miRNA-34a level was determined by fluorescence quantitative PCR to confirm the overexpression. Cell proliferation was analyzed by CCK-8 assay. Cell migration rate was measured by cell scratch assay. Flow cytometry was used to detect apoptosis and analyze cell cycle. Western blot was used to measure the expression levels of ß-catenin, E-cadherin and Vimentin. RESULTS: The expression level of miRNA-34a in prostate cancer tissue was significantly lower than that in prostate paracancerous tissue. Dual-Luciferase reporter gene assay was used to analyze the transcriptional activity of Wnt1 gene. The proliferation and migration of PC3 cells were significantly decreased after overexpression of miRNA-34a, and the differences were statistically significant compared with those in the non-loaded group (p<0.05). Flow cytometry analysis showed that in the overexpression group, the apoptotic rate, as well as the proportion of cells in the G2 phase, was significantly higher than that in the non-loaded group (p<0.05). The ß-catenin level in the nucleus of PC3 cells was significantly reduced after overexpression of miRNA-34a. The total protein levels of ß-catenin and Vimentin were significantly decreased, whereas the level of E-cadherin in the overexpression group was apparently increased, compared with that in the non-loaded group. The Dual-Luciferase reporter gene showed a decrease in the relative fluorescence intensity of Wnt1 after overexpression of miR-34a (p<0.05). CONCLUSIONS: Overexpression of miRNA-34a inhibits Wnt/ß-catenin pathway by regulating the transcriptional activity of Wnt1, thereby regulating the proliferation and migration of PC3 cells and promoting apoptosis.

[Analysis of clinical diagnosis and treatment of 12 cases of intraparotid facial nerve schwannoma].

Objective: To investigate the clinical manifestation and management strategy of intraparotid facial nerve schwannoma. Methods: The clinical data of 12 patients with parotid schwannoma treated in Henan Cancer Hospital from January 2009 to January 2019 were analyzed retrospectively, including 5 males and 7 females, aged from 23 to 72 years. All the 12 patients complained of a mass in the parotid region, of whom 4 patients had local discomfort and pain, and 6 patients had varying degrees of pain during palpation. Ultrasound examination showed solid mass in parotid region in 8 cases and mixed mass in 4 cases. The treatment methods, the relationship between tumor and facial nerve, the modes of treatments and the nerve functions before and after operation were analyzed and summarized with House-Brackmann grade. Results: All 12 patients received surgical treatment: 8 patients underwent tumor resection plus partial or total superficial parotidectomy, 1 patient underwent tumor resection and total parotidectomy, and 3 patients underwent tumor resection, with 1 patient in whom tumor could not be removed completely due to tumor extention to the skull base. In 9 cases, the tumor occurred in the trunk or main branch of the facial nerve, and there was no facial nerve injury occurred after surgery; in 1 case, the tumor occurred in the terminal branch of the facial nerve, and part of the severe small branches of adhesion were cut off during the operation; in 1 case, the total trunk of the facial nerve was not found and the broken end of the nerve could not be found during the operation, so the nerve transplantation was not performed. In 1 case, nerve grafting was performed after nerve transection because it was impossible to separate the trunk of the facial nerve from the tumor during the operation. Preoperatively, House-Brackmann grade (H-B)Ⅰfacial nerve function was shown in 10 patients, H-BⅡ in 1 patient and H-B Ⅴin 1 patient. Postoperatively, the facial nerve function recovered to H-B Ⅰfor 7 patients, H-B Ⅱfor 2 patients, H-B Ⅲ for 1 patient, grade Ⅳ for 1 patient with nerve transplantation, and H-B Ⅴfor 1 patient with a revised surgery due to tumor recurrence. Conclusions: The intraparotid facial nerve schwannoma is rare, and it is easy to be misdiagnosed before operation. Surgery is a main treatment for intraparotid facial nerve schwannoma. Attention should be paid to the protection of facial nerve during operation.

Fusion protein encoded by a CTLA-4 targeted DNA construct binds to human dendritic cells.

Fusing antigens to cytotoxic T-lymphocyte antigen 4 (CTLA-4) represents an effective approach to enhance DNA vaccine efficacy. It has been speculated that the direct targeting of CTLA-4 fusion antigens to antigen-presenting cells (APCs) causes antigens to be processed and presented to T cells more efficiently, leading to a stronger immune response. In the present study, dendritic cells (DCs), the most potent APCs, were generated from human monocytes. The specific binding of CTLA-4 fusion protein to DCs was investigated by flow cytometry. The results showed that the CTLA-4 fusion protein was capable of binding to the B7 molecules on human DCs with specificity.

Analysis of the role of GSK3 in the mitotic checkpoint.

The mitotic checkpoint ensures proper chromosome segregation; defects in this checkpoint can lead to aneuploidy, a hallmark of cancer. The mitotic checkpoint blocks progression through mitosis as long as chromosomes remain unattached to spindle microtubules. Unattached kinetochores induce the formation of a mitotic checkpoint complex (MCC) composed of Mad2, BubR1, Bub1 and Bub3 which inhibits anaphase onset. Spindle toxins induce prolonged mitotic arrest by creating persistently unattached kinetochores which trigger MCC formation. We find that the multifunctional ser/thr kinase, glycogen synthase kinase 3 (GSK3) is required for a strong mitotic checkpoint. Spindle toxin-induced mitotic arrest is relieved by GSK3 inhibitors SB 415286 (SB), RO 318220 (RO) and lithium chloride. Similarly, targeting GSK3ß with knockout or RNAi reduced mitotic arrest in the presence of Taxol. GSK3 was required for optimal localization of Mad2, BubR1, and Bub1 at kinetochores and for optimal assembly of the MCC in spindle toxin-arrested cells. The WNT- and PI3K/Akt signaling pathways negatively regulate GSK3ß activity. Inhibition of WNT and PI3K/Akt signaling, in the presence of Taxol, induced a longer mitotic arrest compared to Taxol alone. Our observations provide novel insight into the regulation of the mitotic checkpoint and its connection to growth-signaling pathways.

Structural and dynamical characteristics of flow units in metallic glasses.

The metallic glasses (MGs) are conjectured to be heterogeneous-their microscopic structures are embedded with localized, soft and loosely packed atomic regions, which are termed as flow units (FUs). Detailed knowledges on the structure and dynamical features of FUs are essential for understanding the plasticity of MGs. In our study, by performing dynamical tests on MGs in molecular dynamics simulations, we show that mechanical hysteretic loops are formed in the strain-stress curves due to the undergoing plastic events. By analyzing the activated times of each atom in different dynamical tests, we map the exact locations of FUs and the distribution of their activation probability in the initial structure of MGs. More importantly, we demonstrate that the FUs are indeed liquid-like according to the Lindemann criterion of melting.

Investigation on the corrosive effect of NH3 during InGaN/GaN multi-quantum well growth in light emitting diodes.

Three series of samples with different NH3 flow rate are grown and the optical and structural properties are investigated. It is found that apart from a positive effect on keeping a high partial pressure of nitrogen to enhance indium incorporation, NH3 may also play a negative effect on indium incorporation during InGaN growth. Especially, when temperature is relatively high, the hydrogen generated from the dissociation of NH3 may suppress the chemical reaction which produces InN, leading to a reduced indium incorporation efficiency during the InGaN layer growth.