Liver-specific deletion of de novo DNA methyltransferases protects against glucose intolerance in high-fat diet-fed male mice.

Alterations to gene transcription and DNA methylation are a feature of many liver diseases including fatty liver disease and liver cancer. However, it is unclear whether the DNA methylation changes are a cause or a consequence of the transcriptional changes. It is even possible that the methylation changes are not required for the transcriptional changes. If DNA methylation is just a minor player in, or a consequence of liver transcriptional change, then future studies in this area should focus on other systems such as histone tail modifications. To interrogate the importance of de novo DNA methylation, we generated mice that are homozygous mutants for both Dnmt3a and Dnmt3b in post-natal liver. These mice are viable and fertile with normal sized livers. Males, but not females, showed increased adipose depots, yet paradoxically, improved glucose tolerance on both control diet and high-fat diets (HFD). Comparison of the transcriptome and methylome with RNA sequencing and whole-genome bisulfite sequencing in adult hepatocytes revealed that widespread loss of methylation in CpG-rich regions in the mutant did not induce loss of homeostatic transcriptional regulation. Similarly, extensive transcriptional changes induced by HFD did not require de novo DNA methylation. The improved metabolic phenotype of the Dnmt3a/3b mutant mice may be mediated through the dysregulation of a subset of glucose and fat metabolism genes which increase both glucose uptake and lipid export by the liver. However, further work is needed to confirm this.

[Determination of triclocarban and triclosan in urine by QuEChERS extraction and ultra-performance liquid chromatography-tandem mass spectrometry].

Objective: To establish a method for the determination of triclocarban (TCC) and triclosan (TCS) in urine by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after purification by QuEChERS. Methods: In May 2022, urine samples were extracted by acetonitrile, purified by QuEChERS, separated by Waters Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm), and eluated with water-acetonitrile as mobile phase gradient at a flow rate of 0.3 ml/min. The detection was conducted in negative ion mode (ESI(-)) and multiple reaction monitoring (MRM) scanning, it was quantified with a internal standard method, and the methodology was verified. Results: The linear ranges of TCC and TCS were 0.5-100.0 µg/L and 1.0-100.0 µg/L, and the correlation coefficients were 0.9997 and 0.9991, respectively. The limits of detection and quantitation of TCC and TCS were 0.17 and 0.33 µg/L, and 0.5 and 1.0 µg/L, respectively. The recoveries of TCC and TCS were 100.1%-102.8% and 96.7%-108.6%, and the relative standard deviations were 4.9%-6.7% and 4.1%-8.3%, respectively, at 2.0, 10.0 and 80.0 µg/L. Conclusion: QuEChERS-UPLC-MS/MS method is simple, rapid, sensitive and reproducible, and can be used for rapid and accurate simultaneous detection of TCC and TCS exposure levels in occupational population.

Predictors of postoperative biochemical remission in lower Knosp grade growth hormone-secreting pituitary adenomas: a large single center study.

PURPOSE: Growth hormone-secreting pituitary adenomas (GH-PAs) with a low Knosp grade are typically associated with a good postoperative biochemical remission (BR) rate. However, a proportion of patients do not achieve remission. In this study, we aimed to investigate predictive factors of postoperative remission for lower Knosp GH-PAs. METHODS: In this retrospective study, we enrolled 140 patients who were diagnosed with lower Knosp (0-2) GH-PAs and received trans-sphenoidal surgery between December 2016 and June 2021 from the largest pituitary tumor surgery center in southern China. The univariate, binary Logistic regression, and receiver operating characteristic curve (ROC) analyses were employed to determine independent predictors and cutoff values of remission. The postoperative outcome was defined as remission using the 2010 consensus criteria of acromegaly. RESULTS: One hundred and thirty six patients (97.1%) achieved gross total resection. The postoperative long-term BR was 68.6%. Empty sella, tumor maximum diameter and postoperative GH levels were independent factors predicting remission. ROC revealed that postoperative 24 h GH ≤ 1.3 ng/mL and ≤ 1.23 ng/mL were valuable predictors for 3-month and long-term remission respectively, and that postoperative 3-month GH ≤ 1.6 ng/mL and tumor maximum diameter ≤ 17 mm were predictors for delayed remission. CONCLUSION: Early postoperative GH levels can be used as predictors of remission. However, BR was not associated with preoperative somatostatin analogs therapy or Knosp grade (0-2). For patients without residual tumor or recurrence and whose GH levels are slightly elevated within 1 year after surgery, adjuvant treatments may not be necessary.

Effects of dexmedetomidine on kidney and brain tissue microcirculation and histology in ovine cardiopulmonary bypass: a randomised controlled trial.

Cardiac surgery requiring cardiopulmonary bypass is associated with postoperative acute kidney injury and neurocognitive disorders, including delirium. Intra-operative inflammation and/or impaired tissue perfusion/oxygenation are thought to be contributors to these outcomes. It has been hypothesised that these problems may be ameliorated by the highly selective α2 -agonist, dexmedetomidine. We tested the effects of dexmedetomidine on renal and cerebral microcirculatory tissue perfusion, oxygenation and histology in a clinically relevant ovine model. Sixteen sheep were studied while conscious, after induction of anaesthesia and during 2 h of cardiopulmonary bypass. Eight sheep were allocated randomly to receive an intravenous infusion of dexmedetomidine (0.4-0.8 µg.kg-1 .h-1 ) from induction of anaesthesia to the end of cardiopulmonary bypass, and eight to receive an equivalent volume of matched placebo (0.9% sodium chloride). Commencement of cardiopulmonary bypass decreased renal medullary tissue oxygenation in the placebo group (mean (95%CI) 5.96 (4.24-7.23) to 1.56 (0.84-2.09) kPa, p = 0.001), with similar hypoxic levels observed in the dexmedetomidine group (6.33 (5.33-7.07) to 1.51 (0.33-2.39) kPa, p = 0.002). While no differences in kidney function (i.e. reduced creatinine clearance) were evident, a greater incidence of histological renal tubular injury was observed in sheep receiving dexmedetomidine (7/8 sheep) compared with placebo (2/8 sheep), p = 0.041. Graded on a semi-quantitative scale (0-3), median (IQR [range]) severity of histological renal tubular injury was higher in the dexmedetomidine group compared with placebo (1.5 (1-2 [0-3]) vs. 0 (0-0.3 [0-1]) respectively, p = 0.013). There was no difference in cerebral tissue microglial activation (neuroinflammation) between the groups. Dexmedetomidine did not reduce renal medullary hypoxia or cerebral neuroinflammation in sheep undergoing cardiopulmonary bypass.

Assessment of indoor bioaerosol exposure using direct-reading versus traditional methods-potential application to home health care.

Home healthcare workers (HHCWs) can be occupationally exposed to bioaerosols in their clients' homes. However, choosing the appropriate method to measure bioaerosol exposures remains a challenge. Therefore, a systematic comparison of existing measurement approaches is essential. Bioaerosol measurements with a real-time, fluorescence-based Wideband Integrated Bioaerosol Sensor (WIBS) were compared to measurements with four traditional off-line methods (TOLMs). The TOLMS included optical microscopic counting of spore trap samples, microbial cultivation of impactor samples, qPCR, and next-generation sequencing (NGS) of filter samples. Measurements were conducted in an occupied apartment simulating the environments that HHCWs could encounter in their patients' homes. Descriptive statistics and Spearman's correlation test were computed to compare the real-time measurement with those of each TOLM. The results showed that the geometric mean number concentrations of the total fluorescent aerosol particles (TFAPs) detected with the WIBS were several orders of magnitude higher than those of total fungi or bacteria measured with the TOLMs. Among the TOLMs, concentrations obtained with qPCR and NGS were the closest to the WIBS detections. Correlations between the results obtained with the WIBS and TOLMs were not consistent. No correlation was found between the concentrations of fungi detected using microscopic counting and any of the WIBS fluorescent aerosol particle (FAP) types, either indoors or outdoors. In contrast, the total concentrations detected with microbial cultivation correlated with the WIBS TFAP results, both indoors and outdoors. Outdoors, the total concentration of culturable bacteria correlated with FAP-type AC. In addition, fungal and bacterial concentrations obtained with qPCR correlated with FAP types AB and AC. For a continuous, high-time resolution but broad scope, the real-time WIBS could be considered, whereas a TOLM would be the best choice for specific and more accurate microbial characterization. HHCWs' activities tend to re-aerosolize bioaerosols causing wide temporal variation in bioparticle concentrations. Thus, the advantage of using the real-time instrument is to capture those variations. This study lays a foundation for future exposure assessment studies targeting HHCWs.

[Survival analysis of malignant tumors in cancer registration areas of Hubei province in China, 2013 to 2015].

Objective: To analyze the survival of newly diagnosed malignant tumors in cancer registration areas of Hubei Province from 2013 to 2015. Methods: From January 1, 2013 to December 31, 2015, all newly diagnosed malignant tumors were collected from cancer registration areas in Hubei Province, and patients were followed up using a combination of active and passive methods. Cancer survival was analyzed using the strs package in Stata software. Observed and expected survival were calculated using the life table and Ederer Ⅱ methods, and the difference in survival rate of patients with different sex, age, urban and rural areas and different cancer species was compared. Results: From 2013 to 2015, 83 987 new malignant tumors were diagnosed in cancer registration areas in Hubei Province, including 45 742 males (54.46%) and 38245 females (45.54%). The overall 5-year relative survival rate was 41.46%, 34.43% for men and 49.63% for women. With the increase of age, the observed survival rate and relative survival rate of patients of different genders showed a decreasing trend. The 5-year relative survival rate of patients with malignant tumors was 47.58% in urban areas and 26.58% in rural areas. The observed survival rate and relative survival rate in rural areas were significantly lower than those in urban areas. The overall 5-year relative survival rates for common malignancies were 20.61% for lung cancer, 15.36% for liver cancer, 22.89% for esophageal cancer, 34.92% for gastric cancer, and 54.87% for colorectal cancer. In addition, the 5-year relative survival rates of common malignant tumors in women were 78.65% for breast cancer and 52.55% for cervical cancer. Conclusions: In Hubei Province, the survival rate of malignant tumors is different among different genders, regions, age groups and cancer species. Prevention and treatment and health education should be strengthened for malignant tumor patients in rural areas and those with high incidence and low survival rate such as liver cancer and lung cancer, and relevant strategies should be formulated according to the gender and age distribution characteristics of different cancer species.

[Clinical and genetics characteristics of adult-onset cerebrotendinous xanthomatosis: analysis of a Chinese pedigree].

Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.

[Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection].

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

[Evaluation of clinical safety and diagnostic efficacy of domestic liver-specific magnetic resonance contrast agent (gadoxetate disodium)].

Objective: To evaluate the clinical safety and diagnostic efficacy of domestic gadoxetate disodium (GdEOBDTPA). Methods: The imaging data from patients with space-occupying liver lesions who underwent GdEOBDTPA enhanced magnetic resonance examination at West China Hospital of Sichuan University between January 2020 and September 2020 were analyzed retrospectively. Clinical indicators were evaluated by the incidental condition of transient severe respiratory motion artifacts (TSM) in the arterial phase to assess the safety profile.The differences in quantitative and qualitative indicators for the risk factors of TSM in the arterial phase between the TSM group and the non-TSM group were compared by t-test and χ2 test. Observational indicators of the accuracy of diagnostic procedures: The 2018 version of the Liver Imaging Reporting and Data System (LI-RADS) was used to evaluate the main signs, auxiliary signs, and LR grades of lesions. Postoperative pathological findings were used as the gold standard for evaluating and diagnosing hepatocellular carcinoma (HCC). Simultaneously, the relative enhancement degree of the liver, the contrast between the lesion and the liver, and the cholangiography in the hepatobiliary phase were evaluated. The McNemar test was used to compare the differences in the diagnostic efficiency of physician 1 and physician 2 in the diagnosis of hepatocellular carcinoma according to the 2018 version of LI-RADS. Results: A total of 114 cases were included in this study. The incidence rate of TSM was 9.6% (11/114). Age [(53.8 ± 11.3) years vs. (55.4 ± 15.4) years, t = 0.465, P = 0.497], body weight [(65.8 ± 11.1) kg vs. (60.8 ± 7.6) kg, t = 1.468, P = 0.228], body mass index [(23.9 ± 3.1) kg/m(2) vs. (23.4 ± 3.0) kg/m(2), t = 0.171, P = 0.680], liver cirrhosis ratio (39 cases vs. 4 cases, χ (2) =1.776, P = 0.183), proportion of mild to moderate pleural effusion (32 cases vs. 4 cases, χ (2) = 0.000, P = 0.986), and proportion of mild to moderate ascites (47 cases vs. 5 cases χ (2) = 0.000, P = 0.991) had no statistically significant difference between the groups of non-TSM and TSM patients. According to the 2018 version of LI-RADS for the LR5 category, there was no statistically significant difference between the two physicians' HCC diagnoses in terms of sensitivity (91.4% vs.86.4%, χ (2) = 1.500, P = 0.219), specificity (72.7 % vs. 69.7%, χ (2) = 0.000, P = 1.000), positive predictive value (89.2% vs. 87.5%, χ (2) = 2.250, P = 0.125), negative predictive value (77.4% vs. 67.6%, χ (2) = 2.250, P = 0.125), and accuracy (86.0% vs. 81.6%, χ (2) = 0.131, P = 0.125). According to physicians 1 and 2 film review results, 91.2% (104/114) and 89.5% (102/114) of the contrast agent were discharged into the common bile duct or duodenum, respectively. In addition, 86.0% (98/114) of the patients had good liver enhancement, and 91.2% (104/114) of the lesions showed low signals relative to the liver background. Conclusion: Domestic gadoxetate disodium has a good clinical safety profile and diagnostic efficacy.

Toripalimab (anti-PD-1) versus high-dose interferon-α2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial.

BACKGROUND: No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM. PATIENTS AND METHODS: From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 [95% confidence interval (CI) 8.31-19.02] months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms [hazard ratio (HR) 1.00; 95% CI 0.65-1.54]. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients' actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%). CONCLUSIONS: Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.

Saturn Anomalous Myriametric Radiation, a New Type of Saturn Radio Emission Revealed by Cassini.

A new radio component namely Saturn Anomalous Myriametric Radiation (SAM) is reported. A total of 193 SAM events have been identified by using all the Cassini Saturn orbital data. SAM emissions are L-O mode radio emission and occasionally accompanied by a first harmonic in R-X mode. SAM's intensities decrease with increasing distance from Saturn, suggesting a source near Saturn. SAM has a typical central frequency near 13 kHz, a bandwidth greater than 8 kHz and usually drifts in frequency over time. SAM's duration can extend to near 11 hr and even longer. These features distinguish SAM from the regular narrowband emissions observed in the nearby frequency range, hence the name anomalous. The high occurrence rate of SAM after low frequency extensions of Saturn Kilometric Radiation and the SAM cases observed during compressions of Saturn's magnetosphere suggest a special connection to solar wind dynamics and magnetospheric conditions at Saturn.

[Morvan syndrome with positive anti LGI1/CASPR2 antibodies in serum/cerebrospinal fluid:a case report and literature review].

To report a typical case of Morvan syndrome with positive anti-leucine rich glioma-inactivated 1(LGI1) and contactin-associated protein 2 (CASPR2) antibodies in serum and cerebrospinal fluid. A 39-years-old female initially presented weakness of extremeties. The main symptoms included paroxysmal limb pain, wheezing, itching, muscle twitching, epilepsy, hypomnesia, dysphoria, apathy, intractable insomnia, salivation and sweating. Tests of electrolytes found hypokalemia (2.7-3.1 mmol/L) and hyponatremia (130-136 mmol/L). Arterial blood gas analysis showed hypoxemia (oxygen saturation 50%-70%). Total thyroxine (TT4) was elevated to 207 nmol/L with positive thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). LGI1and CASPR2 antibodies (CBA method) were positive in both serum and cerebrospinal fluid, and the remaining antibodies related to autoimmune encephalitis and paraneoplastic syndrome were negative. Head MRI was almost normal, while mild abnormalities were found in electroencephalogram. Electromyography showed slightly increased voltage of left quadriceps motor unit potential. After treated with corticosteroids, IVIG and mycophenolate mofetil, the patient completely improved. Cognitive function scores recovered from MoCA/MMSE (16/24) to MoCA/MMSE (26/29). Positivity of LGI1/CASPR2 antibodies both in serum/cerebrospinal fluid are rarely seen in patients with Morvan syndrome. Steroids and immunosuppressants are suggested for treatment as early as possible.

[Regulatory effect of Ac-SDKP on phosphorylated heat shock protein 27/SNAI1 pathway in silicotic rats].

Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 µg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 µg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 µg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeⅠ and Ⅲ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeⅠ and Ⅲ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeⅠ and Ⅲ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeⅠ and Ⅲ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.

[Role of pyroptosis pathway related molecules in acute lung injury induced by gas explosion in rats].

Objective: To explore the role and significance of pyroptosis in gas explosion-induced acute lung injury (ALI) in rats. Methods: In February 2018, 126 SPF male SD rats were selected and randomly divided into blank control group (18 rats) and experimental group (40 m, 80 m, 120 m, 160 m, 200 m and 240 m, 18 per group) . The experimental group carried out gas explosion in the roadway to build the ALI model, the control group did not carry out gas explosion, and other conditions were consistent with the experimental group. Respiratory function indexes such as respiratory frequency (f) , tidal volume (TV) , minute ventilation (MV) and airway stenosis index (Penh) were measured 24 hours after the explosion. 5 rats in each group were sacrificed after anesthesia, Hematoxylin-Eosin (HE) staining was used to observe the pathological morphology of lung tissue. Immunohistochemistry was used to detect the content of Caspase-1. Western blotting was used to detect the content of cell pyroptosis including nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) , Caspase-1, interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in lung tissue related protein expression. Results: The f and MV of rats in the experimental group were higher than those in the control group (P<0.05) . Except for the 40 m and 80 m groups, the TV of rats in the other experimental groups were higher than those in the control group (P<0.05) . Except for the 40 m group, the Penh of rats in the experimental groups were lower than those in the control group (P<0.05) . HE staining showed that the lung tissue of the experimental groups at different distance points showed obvious edema of the pulmonary interstitium and alveoli, a large number of red blood cells and inflammatory cells exuded in the alveolar space, thickening of the pulmonary interstitium, and increased lung injury score (P<0.05) . The results of immunohistochemistry showed that the positive expression of Caspase-1 in each experimental group was higher than that in the control group (P<0.05) . Western blotting results showed that the expression of pyroptosis-related proteins in each experimental group was higher than that in the control group (P<0.05) . Conclusion: Pyroptosis is involved in the pathophysiological process of gas explosion-induced ALI in rats.

[Application of indocyanine green fluorescence visualization in surgical resection of abdominal wall endometriosis].

Objective: To investigate the feasibility, effectiveness and safety of indocyanine green (ICG) navigation in the surgical resection of abdominal wall endometriosis (AWE). Methods: Seven women undergoing surgery for AWE in First Affiliated Hospital of Sun Yat-sen University (from July 1, 2021 to October 1, 2021) were collected. After exposure of the focus, ICG were used intravenously (0.25 mg/kg) as fluorescent dye for the intraoperative evaluation of AWE vascularization. Resection of the AWE was guided by direct visualization of the focus under standard laparoscopy with a near-infrared (NIR) camera head. Surgical margin around the AWE (3, 6, 9 and 12 point) and the margin under the focus were obtained for postoperative pathological examination of endometriosis. Time from injection to fluorescence visualization, the proportion of fluorescence visualization, time of fully resection of AWE, side effects related to the use of ICG, perioperative complications as well as the pathological result of the surgical margins were recorded. Results: ICG fluorescence of the AWE were seen in 5 patients (5/7). The mean time from injection to fluorescence visualization was (46.7±9.8) s. The mean time of fully resection of AWE was (16.4±7.0) minutes. There were no side effects related to the use of ICG. The rate of class-A wound healing was 7/7. All of the surgical margins were confirmed endometriosis-negative by postoperative pathological examination. Conclusion: ICG fluorescence visualization could conduct accurate resection of AWE, which is clinically safe and effective.

[Study on the safety and clinical efficacy of osteotomy after halo pelvic traction in severe scoliosis accompanied with split cord malformation].

Objective: To investigate the safety and clinical efficacy of osteotomy after halo pelvic traction in severe scoliosis accompanied with split cord malformation. Methods: The clinical data of 14 patients with severe scoliosis accompanied with split cord malformation admitted to the Department of Spinal Surgery, Guizhou Orthopedic Hospital from August 2015 to August 2019 were retrospectively analyzed.There were 6 males and 8 females, aged (19.8±5.0) years (range:13 to 34 years). All patients received spinal orthopedic surgery after halo pelvic traction for 3 to 7 weeks.The data of traction time, height, Cobb angle in the main curved coronal plane and sagittal plane, lung function and nutritional status of the patient were collected before and after the treatment. Paired t test was used to compare the evaluation indexes. Results: The traction time of the 14 patients was (35.2±8.3)days (range:20 to 49 days), and the height of them increased from (156.7±7.6)cm (range:141 to 166 cm) before traction to (167.0±6.4)cm (range:154 to 177 cm) after traction（t=-10.49，P<0.01）. The Cobb angle on the main curved coronal plane decreased from (117.4±17.2) ° (range: 91°to 176°) before traction to (56.4±8.1) ° (range:44°to 68°) after traction（t=13.90，P<0.01）. The sagittal Cobb angle decreased from (92.5±11.6) ° (range:62°to 132°) before traction to (41.7±7.7) °(range:29°to 51°) after traction（t=12.11，P<0.01）. No complications such as loosening of nailing and infection occurred during traction, and no decrease of nerve function occurred. Nine patients underwent single segment acromial transpedicle osteotomy and five underwent double segment adjacent asymmetric shortening osteotomy. None of the patients underwent longitudinal fracture resection. The lung function and nutritional status were improved after traction and surgery(all P<0.01). Postoperative follow-up was (22.5±9.1)months (range:12 to 36 months). At the last follow-up, the coronal Cobb angle was (56.3±7.1) °, and the sagittal Cobb angle was (37.7±6.5) °, showing no statistically significant difference from the angle after traction(t=0.16,P=0.88; t=2.28,P=0.32). There was no loss of orthopedic angle. None of the patients had internal fixation displacement, loosening or fracture. Conclusion: The treatment of severe scoliosis with accompanied with split cord malformation by halo pelvic traction is safe and effective, which is worthy of further confirmation by large sample study.

[Four cases of acute renal injury caused by acute dimethyl oxalate poisoning].

Objective: To investigate the clinical features, non-dialysis treatment and prognosis of acute renal injury caused by acute dimethyl oxalate (DMO) poisoning. Methods: Retrospective analysis was performed on the occupational data, clinical manifestation, laboratory examination, treatment methods and prognosis of 4 patients with acute DMO poisoning in July 2020. Results: A large number of white DMO crystals were observed in the workplace. Four patients had acute onset, presenting symptoms such as fatigue, abdominal distension, abdominal cramps and nocturia to varying degrees. Laboratory tests all showed acute kidney injury. Serum creatinine of patients at the onset were 119-835 µmol/L. Patients were given early treatment including rest, protection of renal function, hydration and alkalization of urine, Bailing capsule. Renal function of 4 patients returned to normal, and clinical prognosis was good. Conclusion: Acute DMO poisoning leads to acute renal injury, mainly with renal tubulointerstitial lesions such as hypogravity uria and aseptic leucuria. Active treatment in the early stage has a good short-term clinical prognosis.

[Expression of LIAS and NRF2 in PBMCs from patients with silicosis and their correlation with silicosis].

Objective: To investigate the expression of lipoic acid synthase gene (LIAS) and nuclear factor-erythroid 2-related factor 2 gene (NRF2) in peripheral blood mononuclear cells (PBMCs) from patients with silicosis and their correlation with silicosis. Methods: A total of 45 healthy controls and 107 patients with silicosis were randomly selected in this study in May 2019. PBMCs were isolated from peripheral blood and NRF2 protein expression was detected by immunofluorescence. The mRNA levels of LIAS and NRF2 in PBMCs were determined by real-time PCR. The dose-response relationship beween LIAS and NRF2 mRNA expression levels and their association with silicosis were analyzed by restricted cubic spline (RCS) and logistic regression. Results: Compared with the control group, the number of monocytes in the case group was significantly increased, and the forced expiratory volume in the first second (FEV(1.0)) decreased, the difference was statistically significant (P<0.05) . The positive expression rate of NRF2 in PBMCs of silicosis patients in stage Ⅰ group was significantly higher than that in the control group, and the positive expression rate of NRF2 in silicosis patients in stageⅡ and Ⅲ groups was lower than that in silicosis patients in control group and stage Ⅰ group (P<0.01) . Results of RCS showed that there was a linear dose-response relationship between LIAS and NRF2 mRNA expression (overall correlation test, χ(2)=213.710, P<0.01; non-linear test, χ(2)=1.340, P=0.511) . There was a positive correlation between mRNA expression of LIAS and that of NRF2 (r=0.651, P<0.01) . The results of multivariate analysis showed that LIAS and NRF2 were increased the risk of incidence in silicosis patients with stageⅠ (OR=11.184, 4.332, P<0.05) and NRF2 was the protective factor in silicosis patients with stage Ⅱ and Ⅲ (OR=0.225, 0.208, P<0.05) after adjusting for potential confounding factors including age, education level, BMI and smoking. Conclusion: There is a linear dose-response relationship between the expression of LIAS and NRF2 mRNA in PBMCs of silicosis patients, LIAS and NRF2 are involved in the pathogenesis of silicosis.

[Study on serum metabolomics of combined injury induced by gas explosion in rats].

Objective: To analyze the changes of serum metabolomics in rats with combined injuries caused by gas explosion and explore its possible mechanism. Methods: In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the gas explosion experiment. All 32 SD rats were randomly divided into four groups, control group (not involved in the explosion) , close range (40 m) group, medium range (160 m) group and long range (240 m) group, 8 in each group. The respiratory function at 2 hours and the neural behavior at 48 hours were detected after the explosion. The rats were anesthetized and sacrificed after 48 hours, and the serum, lung, liver and other tissues of the rats were isolated and histopathological changes of lung and liver tissues were observed by HE staining. Serum samples were detected by liquid chromatography-high resolution mass spectrometry (UPLC-Orbitrap Elite/MS) , and metabolic spectrum differences between groups were evaluated by principal component analysis. Differential metabolites were screened and identified, and metabolic pathways were analyzed. Results: Compared with control group, respiratory function indexes (respiratory frequency, minute ventilation, peak inspiratory flow rate, peak expiratory flow rate and 1/2 tidal volume expiratory flow) of rats in different explosion groups were significantly decreased (P<0.05) , but respiration pause, inspiratory time and 2/3 tidal volume required time were significantly increased (P<0.05) in 2 hours after the explosion. However, the residence times of the neurobehavioral indicators of the 40 m group and 160 m group were significantly increased (P<0.05) , and the movement distances were significantly decreased (P<0.05) in 48 hours after the explosion. HE staining results showed that the lung and liver tissues of the rats in the gas explosion group structurally damaged, and the cells were disordered, with inflammatory cell infiltration, bleeding and edema. Metabonomics analysis showed that there were significant differences in metabolic profiles between groups. A total of 18 differential metabolites were identified in serum samples, including aconitum acid, citric acid, niacinamide and pyruvate, which involved in 12 major metabolic pathways, including the glutamic acid and glutamine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glyoxylic acid and dicarboxylic acid metabolism, phenylalanine metabolism, nicotinic acid and nicotinamide metabolism, citric acid cycle (TCA cycle) . Conclusion: Gas explosion can cause multi-organ system damage in rats, the mechanism of which may be related to the biosynthesis of alanine, tyrosine and tryptophan, metabolism of niacin and niacinamide, metabolism of acetaldehyde and dicarboxylic acid, and TCA cycle, etc.

[Influences of gas explosion on acute blast lung injury and time phase changes of pulmonary function in rats under real roadway environment].

Objective: The aims of this study were to investigate the effect of gas explosion on rats and to explore the pulmonary function alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment. Methods: In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the real gas explosion roadway environment, fixed the cage and set the explosion parameters. 72 SD rats, male, SPF grade, were randomly divided into nine groups by completely random grouping method according to their body weight: control group, close range group (160 m) , and long range group (240 m) . In each group, there were wound groups (24 h group and 48h group, 8/group, total 48 in six groups) and no wound groups (8/group, total 24 in three groups) . Except for the control group, the other groups were placed in cages at different distances under anesthesia, the experiment of gas explosion was carried out by placing the rats in a position that could force the lungs. The changes of respiratory function of the rats in the non-invasive group were monitored with pulmonary function instrument at 2 h, 24 h, 48 h, 72 h and 168h after the explosion, and were killed under anesthesia 7 days later; the rats in invasive groups were anesthetized and killed at 24 h, 48 h and 168 h, respectively. Gross observation, lung wet-dry ratio and lung histopathology were performed. Results: Compared with the control group, f (respiratory frequency, f) , MV (minute ventilation, MV) , PEF (peak expiratory flow rate, PEF) , PIF (peak inspiratory flow rate, PIF) and EF50 (1/2 tidal volume expiratory flow, EF50) of rats in the close and long range groups decreased significantly after gas explosion 2 h. PAU (respiration pause, PAU) , Te (expiratory time, Te) , Ti (inspiratory time, Ti) and Tr (relaxation time, Tr) were significantly increased (P<0.05) . After 48 h, TV (tidal volume, TV) , Penh (enhanced respiration pause, Penh) , PAU, and PIF of rats in the long range group were significantly increased (P<0.05) . After 72 h, MV in the long range group was significantly decreased (P<0.05) . Compared with the control group, Penh, PAU, Ti and Te were significantly decreased after 168 h in the close and long range groups, with statistical significance (P<0.05) . At the same time, the body weight of rats in different range groups was significantly decreased (P<0.05) . In addition, both HE staining and routine observation of lung tissues of rats in different range groups showed that gas explosion caused pulmonary edema, obviously congested pulmonary capillaries, a large number of inflammatory cells and infiltrated red blood cells. Conclusion: Gas explosion in real roadway environment can cause the change of respiratory function phase and lung tissue damage in rats, suggesting that the model of gas explosion-induced ABLI has been initially established successfully, which would provide a basis for further study on the pathogenesis of ABLI.