[Pathogenic characterization of Klebsiella pneumoniae resistant to carbapenems and polymyxin].

Objective: Analysis and investigation of pathogenic characteristics of polymyxin-and carbapenem-resistant Klebsiella pneumoniae (PR-CRKP). Methods: A total of 23 PR-CRKP strains isolated from clinical specimens from the General Hospital of Southern Theater Command from March 2019 to July 2021 were retrospectively collected, Whole-genome sequencing was performed on 23 PR-CRKP strains, resistance genes were identified by comparison of the CARD and the ResFinder database, high-resolution typing of PR-CRKP strains was analyzed by core genomic multilocus sequencing (cgMLST) and single nucleotide polymorphism (SNP); polymyxin resistance genes were determined by PCR and sequencing. Results: All PR-CRKP strains were KPC-2 producing ST11 types. cgMLST results showed that the evolutionary distance between the PR-CRKP strains and Klebsiella pneumoniae in mainland China was 66.44 on average, which is more closely related than foreign strains; the 23 PR-CRKP strains were divided into 3 main subclusters based on SNP phylogenetic trees, with some aggregation among Clade 2-1 in the isolation department and date. The two-component negative regulatory gene mgrB has seven mutation types including point mutations, different insertion fragments and different insertion positions. Conclusion: The close affinity of PR-CRKP strains indicate the possibility of nosocomial clonal transmission and the need to strengthen surveillance of PR-CRKP strains to prevent epidemic transmission of PR-CRKP.

[Scimitar syndrome with pulmonary sequestration containing carcinoma: a case report].

We reported the manifestations, auxiliary examination, and treatment courses of a case of scimitar syndrome with pulmonary sequestration containing carcinoma. The clinical characteristics of scimitar syndrome with pulmonary sequestration, pulmonary sequestration containing carcinoma were summarized based on the data of this case and the related literatures before January 2022. Scimitar syndrome can coexist with ipsilateral pulmonary sequestration. Because sequestered lung tissue has a risk of malignant transformation, a cancer screening test is useful for early diagnosis and timely treatment.

[Repeated stellate ganglion blockade for the treatment of ventricular tachycardia storm in patients with nonischemic cardiomyopathy: a new therapeutic option for patients with malignant arrhythmias].

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.

[Association and gender difference analysis of obstructive sleep apnea hypopnea syndrome and liver injury].

Objective: To investigate the correlation and sex difference between obstructive sleep apnea hypopnea syndrome (OSAHS) and liver injury. Methods: A total of 974 OSAHS patients (444 cases of mild to moderate, 530 cases of severe) and 111 cases of simple snoring in the First Affiliated Hospital of Fujian Medical University and Zhangzhou Municipal Hospital from November 2015 to September 2019 were included in the study. The basic information of the patients was obtained through face-to-face survey with self-made questionnaire, physical examination, sleep monitoring and blood biochemical and liver function index detection were carried out among the included subjects. Multiple logistic regression model was used to analyze the correlation between OSAHS and liver injury and the gender differences. Results: The subjects were (50±14) years old, including 841 males (77.5%). Statistically significant differences in total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), fasting blood glucose, alamine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, gamma glutamyltransferase (GGT), the rate of elevated ALT, AST and liver injury were observed among the three groups (all P values<0.05). There was no significant difference in total bilirubin and ALP among all groups (all P values>0.05). Multivariate logistic regression showed that after adjusting for confounding factors, severe OSAHS was positively correlated with liver injury [OR (95%CI): 2.25 (1.22-4.14)]. Subgroup analysis by gender showed that severe OSAHS was positively correlated with liver injury in males [OR (95%CI): 2.20 (1.04-4.65)], but not in females, mild to moderate OSAHS [OR (95%CI): 1.56 (0.52-4.71)] or severe OSAHS [OR (95%CI): 2.07(0.64-6.75)], after adjusting for confounding factors. Conclusion: Severe OSAHS is positively correlated with liver injury in males, while female OSAHS is not associated with liver injury.

Partial thyroxine-binding globulin deficiency in a family with coding region mutations in the TBG gene.

PURPOSE: T4-binding globulin (TBG) is the main thyroid hormone (TH) transporter present in human serum. Inherited thyroxine-binding globulin (TBG) deficiency is caused by mutations in the TBG (SERPINA7) gene, which is located on the X chromosome. This study was performed to report and evaluate coding region mutations in TBG gene for partial thyroxine-binding globulin deficiency. METHODS: A pedigree spanning four generations is described in this study. The proband is a female with partial TBG deficiency. All members of this pedigree underwent thyroid function tests, while Sanger sequencing was used to identify the TBG gene mutations. Bioinformatics databases were used to evaluate the deleterious effects of the mutation(s). Two hundred and seven unrelated individuals were used to evaluate the thyroid function of individuals with different TBG mutations. A one-way ANOVA was used to analyze the impact of the TBG mutations on thyroid function. RESULTS: TBG gene sequencing results revealed that the proband had a novel mutation in codon 27 leading to alanine to valine substitution (p.A27V). This mutation was associated with lower serum T4 levels (p < 0.0001) when compared to the groups that did not carry the mutation. The previously reported p.L283F mutation was also found in the proband. The hemizygous p.L283F individuals presenting with lower T4 serum and TBG levels (p < 0.001) when compared to wildtype males and females. Both mutations were deleterious upon SIFT and PolyPhen-2 evaluation. CONCLUSION: Associated with partial thyroxine-binding globulin deficiency, this study reports a novel p.A27V mutation in the TBG gene.

[Research advances in the relationship between nonalcoholic fatty fiver disease and sarcopenia].

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes for chronic liver diseases, which progress gradually from nonalcoholic type simple fatty liver disease to hepatitis, cirrhosis and even liver failure and hepatocellular carcinoma. Sarcopenia is a progressive disease characterized by reduced skeletal muscle mass and function in association to metabolic dysfunctions. Recent studies have shown that the occurrence and development of NAFLD and sarcopenia are related, and there is a common base for the pathogenesis between the two, which may promote each other for mutual risk factors. This article reviews the current research progress of this field in order to clinically further understand the pathogenesis and intrinsic links between the two to look for appropriate interventions.

Analysis of thrombin-antithrombin complex contents in plasma and hematoma fluid of hypertensive intracerebral hemorrhage patients after clot removal.

BACKGROUND AND PURPOSE: Animal experiments indicate that the cerebral thrombin is associated with secondary brain damage after intracerebral hemorrhage (ICH). This study was aimed to investigate the concentrations of thrombin-antithrombin complex (TAT) in hematoma fluid and plasma of the patients with ICH after surgery and analyze the correlation between TAT complex levels and severity of ICH. METHODS: Sixty patients with ICH were enrolled. Craniotomy for removal of intracranial blood clot was performed within 24h after ICH. Hematoma fluid and plasma were collected on postoperative days 1, 2, and 4. The plasma obtained from healthy subjects and cerebrospinal fluid from patients without cerebrovascular diseases served as controls, respectively. Enzyme-linked immunosorbent assay was used to determine the concentrations of TAT complex in the patients and controls. RESULTS: TAT complex concentrations in both postoperative plasma and hematoma fluid of patients with ICH were significantly higher than those of the controls (P<0.01). In patients with ICH, hematoma fluid had a higher TAT complex level than plasma (P<0.01). The preoperative hemorrhage volume and postoperative TAT complex levels in plasma and hematoma fluid correlated positively with National Institutes of Health stroke scale and negatively with Glasgow coma score (P<0.01). CONCLUSION: This study indicates that TAT complex levels of plasma and hematoma fluid correlate positively with the severity of ICH. Determination of the plasma TAT complex concentration is helpful for the evaluation of the severity of post-ICH brain injury.

Study of expression levels and clinical significance of miR-503 and miR-375 in patients with esophageal squamous cell carcinoma.

OBJECTIVE: This study aims to investigate the expression levels and clinical significance of miR-503 and miR-375 in patients with esophageal squamous cell carcinoma. PATIENTS AND METHODS: 40 cases of cancer tissues and adjacent tissues in patients with esophageal squamous cell carcinoma were collected from March 2017 to September 2017 in the Department of Gastroenterology in the First Affiliated Hospital of Henan Polytechnic University. qRT-PCR was used to analyze the expressions of miR-503 and miR-375 in cancer tissues and adjacent normal tissues. The association between their expressions and the gender, age, degree of tumor differentiation, TNM staging, presence or absence of lymph node metastasis, and other clinicopathological characteristics of patients with esophageal squamous cell carcinoma was analyzed. RESULTS: The results showed that the expression level of miR-503 in esophageal squamous cell carcinoma tissues (6.83±2.14) was significantly higher than that in adjacent tissues (2.45±1.13). The expression level of miR-375 in esophageal squamous cell carcinoma tissues (3.75±1.06) was significantly lower than that in adjacent tissues (7.45±1.13). The expression levels of miR-503 and miR-375 in esophageal squamous cell carcinoma were related to the existence of lymph node metastasis, degree of differentiation of esophageal squamous cell carcinoma and TNM staging (p<0.001). There was no correlation between the expressions of miR-503 and miR-375 and the age, gender and tumor size of patients (p>0.05). CONCLUSIONS: miR-503 was highly expressed in esophageal squamous cell carcinoma and miR-375 was lowly expressed in esophageal squamous cell carcinoma. miR-503 and miR-375 were closely related to the lymphatic metastasis, degree of differentiation and TNM staging of the tumor.

Anti-tumor effect of endostatin in a sleep-apnea mouse model with tumor.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with cancer incidence and mortality. The underlying mechanism is unclear. This study aims to evaluate the influence of intermittent hypoxia (IH), a novel hallmark of OSA, on tumor and to access the anti-tumor effect of endostatin on a mouse model with OSA. METHODS: The C57BL/6 J mice were randomly classified into four groups: control (normoxia) (CTL), control plus endostatin (CTL + ED), IH, and IH plus endostatin (IH + ED). Mice in IH and IH + ED groups were subjected to IH 8 h per day in 5 weeks. Lewis lung cancer cells were injected into the flank of each mouse after 1 week of IH exposure. Endostatin was also intraperitoneally injected after tumor volume reached about 200 mm3. The maximum standard uptake values (SUVmax) were detected by micro-positron emission tomography-computed tomography (micro-PET-CT) imaging prior and post-endostatin administration. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) were determined for evaluating the anti-tumor effect of endostatin among the normoxia and IH conditions. RESULTS: Mice had higher SUVmax in the IH group than the CTL group (p < 0.01). When compared with mice in the CTL group, those in the IH group had significantly greater MVD values (p < 0.001). The SUVmax can be attenuated by endostatin both in the CTL (p < 0.01) and IH conditions (p < 0.001). When compared with CTL group, mice in the IH group had increased MVD values (p < 0.001) and VEGF expression both at mRNA (p < 0.05) and protein levels (p < 0.001 in western blotting results). Treatment with endostatin attenuated serum and tissue VEGF levels, lowering the MVD values. As compared to normoxia condition, the endostatin-therapeutic effects were more significant under the IH condition (p < 0.05 in western blotting results). CONCLUSIONS: Micro-PET-CT imaging is a promising non-invasive technique to evaluate the tumor metabolic characteristics under IH condition in vivo. The anti-tumor effect of endostatin under IH condition is superior to that of the normoxia condition.

Effect of naturally reduced ovarian function on plasma lipoprotein and 27-hydroxycholesterol levels in baboons (Papio sp.).

Female baboons over 15 years of age develop irregular menstrual cycles, an indication of declining ovarian function similar to that occurring in perimenopausal women. To determine the effect of declining ovarian function on plasma lipoprotein metabolism and plasma oxysterols, we measured plasma lipoprotein and 27-hydroxycholesterol levels in 86 female baboons from 15-28 years of age with regular (n = 51) and irregular (n = 35) menstrual cycles. We sampled blood and liver while they were consuming a basal diet and after consuming a high cholesterol and high fat diet for 7 weeks. On the basal diet, baboons with irregular cycles had higher VLDL + LDL/HDL cholesterol ratios (P = 0.034). After consuming the HCHF diet for 7 weeks, total plasma (P < 0.001) and VLDL + LDL (P < 0.001) cholesterol concentrations and VLDL + LDL/HDL sterol ratios (P < 0.001) increased in both cycle groups; whereas HDL cholesterol concentrations increased only in baboons with regular cycles (P = 0.009). As a result, HDL cholesterol concentrations (P = 0.006) were lower and VLDL + LDL/HDL cholesterol ratios (P = 0.002) were higher in baboons with irregular cycles on the HCHF diet. Plasma 27-hydroxycholesterol concentrations were higher in baboons with regular cycles than in those with irregular cycles on both basal (P = 0.018) and HCHF (P = 0.037) diets and were positively correlated (P < 0.001) with hepatic sterol 27-hydroxylase activities on both diets. Hepatic sterol 27-hydroxylase activities were negatively correlated with the VLDL + LDL/HDL cholesterol ratios on the HCHF diet (r = -0.342, P = 0.033). These results suggest that declining ovarian function changes the plasma lipoprotein pattern to one that is more atherogenic. Ovarian failure is also associated with decreased concentrations of plasma 27-hydroxycholesterol (the major oxysterol of plasma), and the decrease in plasma 27-hydroxycholesterol concentration was due to the decrease in hepatic sterol 27-hydroxylase activity. The effects of ovarian failure on plasma lipoprotein metabolism and plasma 27-hydroxycholesterol may be mediated by the decreased production of estrogen in perimenopausal baboons. Thus, the perimenopausal baboon is an excellent model for menopause and can be used for studies that cannot be conducted in women.

The pineal hormone melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in vivo.

Melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in a dose-dependent manner. Total DNA-adduct formation after in vivo administration of 300 mg/kg safrole measured by 32P-postlabeling analysis of carcinogen-modified DNA in rat liver was 36,751 +/- 2290 counts/min/10 micrograms DNA. Coadministration of 300 mg/kg safrole with either 0.2 mg/kg (low dose) or 0.4 mg/kg (high dose) melatonin reduced DNA-adduct formation induced by safrole to 22,182 +/- 987 counts/min/10 micrograms DNA and 462 +/- 283 counts/min/10 micrograms DNA, respectively. Circulating melatonin concentrations at the termination of the study in safrole, low melatonin and high melatonin groups were 50 +/- 8, 3140 +/- 430 and 10,040 +/- 2610 pg/ml serum, respectively. The results suggest that melatonin protects against safrole associated DNA damage.

Melatonin's inhibitory effect on growth of ME-180 human cervical cancer cells is not related to intracellular glutathione concentrations.

The effects of various concentrations of melatonin on the growth of ME-180 human cervical cancer cells in vitro was examined. Melatonin at a concentration of 2 mM inhibited the growth of the cells after 48 h of melatonin treatment. At concentrations of 2 microM or 0.1 mM melatonin had no effect on cell proliferation. To determine whether the inhibitory effect of melatonin on the growth of the cervical cancer cells was linked to intracellular glutathione concentrations, experiments were performed in which intracellular glutathione levels were depressed by the addition of buthionine sulfoximine to the incubation medium 24 h before the addition of melatonin. The results show that 2 mM melatonin treatment still inhibits the growth of cells when glutathione levels are depressed by 95%. Even with depressed glutathione levels, 0.1 mM melatonin still had no effect on cell growth. Thus, melatonin's ability to inhibit ME-180 cervical cell growth in vitro may be independent of intracellular glutathione concentrations. It was also found that during one passage the intracellular glutathione levels of cervical cancer cells gradually decreases. When 4.5-day-old medium was replaced with new medium, intracellular glutathione levels partially recovered within 36 h. This suggests that the observed gradual reduction of cellular glutathione during incubation was a result of a reduction of some constituent in the medium after prolonged culture of the cells.

Melatonin stimulates brain glutathione peroxidase activity.

Exogenously administered melatonin causes a 2-fold rise in glutathione peroxidase activity within 30 min in the brain of the rat. Furthermore, brain glutathione peroxidase activity is higher at night than during the day and is correlated with high night-time tissue melatonin levels. Glutathione peroxidase is thought to be the principal enzyme eliminating peroxides in the brain. This antioxidative enzyme reduces the formation of hydroxyl radicals formed via iron-catalyzed Fenton-type reactions from hydrogen peroxide by reducing this oxidant to water. Since the hydroxyl radical is the most noxious oxygen radical known, induction of brain glutathione peroxidase might be an important mechanism by which melatonin exerts its potent neuroprotective effects.

Effect of dietary lipids on hepatic and extrahepatic sterol 27-hydroxylase activity in high- and low-responding baboons.

Our previous studies found that low low-density lipoprotein (LDL)-responding baboons compared with high LDL-responding baboons have higher hepatic sterol 27-hydroxylase activity when consuming a high-cholesterol and high-fat (HCHF) diet. The present studies were conducted to determine whether the extrahepatic activity of sterol 27-hydroxylase is also higher in low-responding baboons and to assess whether the enzyme is regulated at the protein level. We measured the hepatic sterol 27-hydroxylase activity and protein level and plasma 27-hydroxycholesterol concentration in six low- and six high-responding baboons on both the basal and the HCHF diet. We also compared the sterol 27-hydroxylase activity in the adrenal gland and 27-hydroxycholesterol concentration in blood lymphocytes from high- and low-responding baboons consuming the HCHF diet. With the HCHF diet, the plasma 27-hydroxycholesterol concentration and hepatic sterol 27-hydroxylase activity and protein level increased rapidly in low responders, but not in high responders. Blood lymphocytes of low-responding baboons cultured in the presence of lipoprotein-deficient serum (LPDS) had lower cholesterol concentrations than those from high-responding baboons. Addition of exogenous 27-hydroxycholesterol to the culture medium of blood lymphocytes decreased the cellular cholesterol concentration. Plasma 27-hydroxycholesterol and hepatic sterol 27-hydroxylase activity and protein levels were negatively correlated with the plasma VLDL + LDL cholesterol concentration and VLDL + LDL/HDL cholesterol ratio after 6 weeks on the HCHF diet, but not on the chow diet. The results suggest that sterol 27-hydroxylase activity in both hepatic and extrahepatic tissues attenuates the dietary responsiveness in baboons, and the enzyme activity is not regulated by the specific activity of the protein.

Melatonin affords protection against kainate-induced in vitro lipid peroxidation in brain.

Melatonin protection against in vitro kainic acid-induced oxidative damage in rat brain is shown. Brain disrupted cell homogenates were incubated with different concentrations of kainate and with or without different concentrations of melatonin. The concentration of malonaldehyde and 4-hydroxyalkenals was measured as an index of lipid peroxidation. When administered together with kainate, melatonin produced a concentration-dependent decrease in kainate-induced lipid peroxidation ranging from 20% to 100%. Moreover, when added to the reaction mixture alone, melatonin decreased the basal level of lipid peroxidation compared to controls.