[Clinical characteristics of programmed cell death-1 inhibitor-associated hypophysitis].

Objective: To explore the clinical features of programmed cell death-1 (PD-1) inhibitor-associated hypophysitis and improve the understanding of the disease. Methods: For the present retrospective case series study, the clinical data of patients with PD-1 inhibitor-associated hypophysitis who were treated at the Affiliated Hospital of Hebei University and the 3rd Hospital of Hebei Medical University from January 2020 to May 2023 were collected for analysis of clinical manifestations and prognosis. Results: Fifteen cases of PD-1 inhibitor-induced hypophysitis were included, with 13 males and 2 females. The mean age of onset was (62.1±7.5) years, and the median time of onset was 6.5 (4.7, 11.6) cycles of PD-1 inhibitor. At diagnosis, 14 patients complained of gastrointestinal symptoms, and 12 patients complained of fatigue. There were 12, 1, 1, 5, and 1 cases of hyponatremia, hypokalemia, hypoglycemia, hypotension, and fever, respectively. Secondary adrenocortical insufficiency occurred in all cases. Moreover, four patients had secondary hypothyroidism, and two patients had secondary hypogonadism. Posterior pituitary hypofunction was not found. Pituitary MRI showed one case each of vacuolar sella turcica, pituitary cystic lesion, pituitary stalk slightly shifted to the left, high metabolism in the sella turcica, and pituitary abnormal signal, while no abnormalities were found in 11 cases. The follow-up time was (47.66±11.93) weeks. At the last follow-up, one patient's serum levels of adrenocorticotropic hormone and cortisol returned to normal. Conclusions: Hypophysitis associated with PD-1 inhibitors occurs later, and gastrointestinal symptoms and fatigue are the most common clinical manifestations. PD-1 inhibitor-associated hypophysitis mainly manifests as adrenocortical hypofunction, and some cases manifest as hypothyroidism and hypogonadism. In addition, patients with PD-1 inhibitor-associated hypophysitis show no obvious imaging changes in the pituitary gland.

[Treatment of early capsular blockage syndrome with Nd:YAG laser anterior capsulotomy containing neodymium-doped yttrium aluminum garnet in a case].

A 62-year-old female patient presented with no improvement in vision 10 days after undergoing cataract extraction in the right eye. The unaided visual acuity in the right eye was 0.1, and examination with a slit lamp revealed the presence of the intraocular lens with an increased gap between the intraocular lens and the posterior capsule. Anterior segment optical coherence tomography showed a distance of 3.236 mm between the posterior capsule and the posterior surface of the intraocular lens. Based on the medical history, ocular examination, and auxiliary examinations, a diagnosis of right eye capsular blockage syndrome was made. Nd:YAG laser capsulotomy was performed at the anterior capsule outside the optical zone of the intraocular lens. One week later, the posterior capsule adhered to the posterior surface of the intraocular lens, and there was a significant improvement in vision compared to before the procedure.

[The effect of HOXC10 gene on biological behaviors of glioma cells and mechanism in tumor microenvironment].

Objective: To study the effects of Homeobox C10 (HOXC10) on biological characteristics such as migration, invasion and proliferation of glioma cancer cells and to explore the role of HOXC10 gene in glioma microenvironment. Methods: The expression level of HOXC10 in high grade glioma (glioblastoma) and low grade glioma and its effect on patient survival were analyzed by using The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) database. Hoxc10-siRNA-1, HOXC10-siRNA-2 and siRNA negative control (NC) were transfected into U251 cells according to the operation instructions of HOXC10-siRNA transfection. 100 ng/ mL recombinant protein chemokine ligand 2 (reCCL2) was added into the transfection group, and was labeled as HOXC10-siRNA-1+ reCCL2 and HOXC10-siRNA-2+ reCCL2 groups. The expressions of HOXC10 mRNA and target protein in each group was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and western blot. The proliferation ability of cells in each group was detected by cell counting kit 8 (CCK8) method. The migration ability of cells was detected by Transwell assay and Nick assay, and cell apoptosis was detected by flow cytometry. The expression of chemokines in each group was detected by multiple factors. Co-incubation assays were performed to determine the role of HOXC10 and chemokine ligand 2 (CCL2) in recruiting and polarizing tumor-associated macrophages (M2-type macrophages). Results: The median expression level of HOXC10 in high grade gliomas was 8.51, higher than 1.00 in low grade gliomas (P<0.001) in TCGA database. The median expression level of HOXC10 in high grade gliomas was 0.83, higher than 0.00 in low grade gliomas (P=0.002) in CGGA database. The 5-year survival rate of patients with high HOXC10 expression in TCGA database was 28.2%, lower than 78.7% of those with low HOXC10 expression (P<0.001), and the 5-year survival rate of patients with high HOXC10 expression in CGGA database was 20.3%, lower than 58.0% of those with low HOXC10 expression (P<0.001). The numbers of cell migration in HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (45±3) and (69±4) respectively, lower than (159±3) in NC group (P<0.05). The cell mobility of HOXC10-siRNA-1 group and HOXC10-siRNA-2 group at 48 hours were (15±2)% and (28±4)% respectively, lower than (80±5)% of NC group (P<0.05). The expressions of vimentin in HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (141 740.00±34 024.56) and (94 655.00±5 687.97), N-cadherin were (76 810.00±14.14) and (94 254.00±701.45), ß-catenin were (75 786.50±789.84) and (107 296.50±9 614.53), lower than (233 768.50±34 114.37), (237 154.50±24 715.50) and (192 449.50±24 178.10) of NC group (P<0.05). The A value of HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (0.44±0.05) and (0.32±0.02) at 96 hours, lower than 0.92±0.12 of NC group (P<0.05). The apoptosis rates of HOXC10-siRNA-1 group and HOXC10 siRNA-2 group were (10.23±1.24)% and (13.81±2.16)%, higher than (4.60±0.07)% of NC group (P<0.05). The expression levels of CCL2 in U251 cells in HOXC10-siRNA-1 and HOXC10-siRNA-2 groups were (271.63±44.27) and (371.66±50.21), lower than (933.93±29.84) in NC group (P<0.05). The expression levels of CCL5 (234.81±5.95 and 232.62±5.72), CXCL10 (544.13±48.14 and 500.87±15.65) and CXCL11 (215.75±15.30 and 176.18±16.49) in HOXC10-siRNA-1 and HOXC10-siRNA-2 groups were higher than those in NC group (9.98±0.71, 470.54±18.84 and 13.55±0.73, respectively, P<0.05). The recruited numbers of CD14(+) THP1 in HOXC10-siRNA-1 and HOXC10-siRNA-2 groups were (159.33±1.15) and (170.67±1.15), respectively, lower than (360.00±7.81) in NC group (P<0.05), while addition of reCCL2 promoted the recruitment of CD14(+) THP1 cells (287.00±3.61 and 280.67±2.31 in HOXC10-siRNA-1+ reCCL2 group and HOXC10-siRNA-2+ reCCL2 group, respectively, P<0.05). The expressions level of M2-type macrophage-related gene TGF-ß in HOXC10-siRNA-1 group and HOXC10-siRNA-2 group were (0.30±0.02) and (0.28±0.02), respectively, lower than (1.06±0.10) in NC group (P<0.05). The expressions level of M1-related gene NOS2 in HOXC10-siRNA-1 and HOXC10-siRNA-2 were (11 413.95±1 911.85) and (5 894.00±945.21), respectively, higher than (13.39±4.32) in NC group (P<0.05). Conclusions: The expression of HOXC10 in glioma is high and positively correlated with the poor prognosis of glioma patients. Knockdown of HOXC10 can inhibit the proliferation, migration and metastasis of human glioma U251 cells. HOXC10 may play an immunosuppressive role in glioma microenvironment by promoting the expression of CCL2 and recruiting and polarizing tumor-associated macrophages (M2 macrophages).

[Perifosine inhibits biofilm formation of Pseudomonas aeruginosa by interacting with PqsE protein].

To explore the biofilm inhibitory efficacy of perifosine against Pseudomonas aeruginosa (P. aeruginos) and its mechanisms. Twenty-fourwell plate was used to form biofilms at the bottom and crystal violet staining was used to determine the biofilm inhibitory effects of perifosine against P. aeruginosa, the wells without perifosine was set as control group. Glass tubes combined with crystal violet staining was used to detect the gas-liqud interface related bioiflm inhibitory effects of perifosine, the wells without perifosine was set as control group. Time-growth curved was used to detect the effects of perifosine on the bacteial planktonic cells growth of P. aeruginosa, the wells without perifosine was set as control group. The interaction model between perifosine and PqsE was assessed by molecular docking assay. The inhibitory effects of perifosine on the catalytic activity of PqsE was determined by detection the production of thiols, the wells without perifosine was set as control group. Binding affinity between perifosine and PqsE was detected by plasma surface resonance. The biofims at the bottom of the microplates and air-liquid interface were effectively inhibited by perifosine at the concentration of 4-8 µg/ml. There was no influence of perifosine on the cells growth of P. aeruginosa. The resuts of molecular docking assay indicates that perifosine could interacted with PqsE with the docking score of -10.67 kcal/mol. Perifosine could inhibit the catalytic activity of PqsE in a dose-dependent manner. The binding affinity between perifosine and PqsE was comfirmed by plasma surface resonance with KD of 6.65×10-5mol/L. Perifosine could inhibited the biofilm formation of P. aeruginosa by interacting with PqsE.

[Susceptibility of drug-resistant staphylococci isolated from different parts of the ocular anterior segment to common ophthalmic antibiotics].

Objectie To investigate the susceptibility of drug-resistant staphylococci isolated from different parts of the anterior segment to levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin. Methods: Experimental Study. A total of 67 patients with anterior segment infection (33 cases of conjunctivitis, 6 cases of bacterial keratitis, 7 cases of blepharitis, 9 cases of neonatal dacryocystitis, 9 cases of neonatal dacryocystitis, 1 case of adult dacryocystitis and 11 cases of other infectious eye diseases) were collected from the conjunctival sac, cornea, eyelid margin and lacrimal sac. Minimum inhibitory concentration (MIC) determination of methicillin-resistant Staphylococcus (MRS) strains and ß-lactamase-producing (ß-Lac) strains by a micro-liquid-based method, according to the M100 standard of the American Institute for Clinical and Laboratory Standardization Susceptibility and resistance determinations were made. Data were statistically analyzed using Chi-square or Fisher's exact test. Results: Thirty-five MRS, 30 ß-Lac and 2 ß-Lac MRS isolates were identified from 67 multidrug-resistant Staphylococcus . There were 3, 9, 4, and 19 MRS isolates isolated from the lacrimal sac, cornea, eyelid margin and conjunctival sac, accounting for 3/4, 9/12, 4/8, 19/43 (44.2%) of the isolated sites respectively. There were 1, 3, 3, and 23 ß-Lac isolates, accounting for 1/4, 3/12, 3/8 and 23/43 (53.5%) of the isolated sites, respectively. The highest proportion of ß-Lac isolates isolated from patients with a diagnosis of conjunctivitis was 17 (25.3%) from the conjunctival sac. Among the MRS strains isolated from the cornea and lacrimal sac, 5 (7.5%) and 3 (4.5%) were from patients diagnosed with bacterial keratitis and neonatal tear, respectively. The number of MRS strains and ß-Lac isolates isolated from patients with a diagnosis of blepharitis were both 3 (4.5%) from the lid margin.Among the strains isolated from the eyelid margin and the conjunctival sac, drug-resistant Staphylococcus epidermidis was the main strain, the drug-resistant Staphylococcus aureus was the major isolates in lacrimal sac and cornea. Among the 35 MRS isoaltes, 25, 24, 12, 12, and 11 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, clindamycin and tobramycin, and the sensitivity rates were 71.4%, 68.6%, 34.3%, 34.3% and 31.4%, the difference was statistically significant (χ2=22.756, P<0.001), The sensitivity rates of levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin against MRS isolates from the anterior segment were both statistically significant differences (χ2=18.493, 11.594, 8.906, 9.841, 16.059; all P<0.05). The susceptibility rates of MRS isolates against five antibiotics was statistically significant differences (χ2=33.080, P<0.001). Among the 30 ß-Lac isolates, 27, 22, 19, 16, and 8 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, tobramycin and clindamycin, and the sensitivity rates were 90.0 % , 73.3%, 63.3%, 53.3% and 26.7%, the difference was statistically significant (χ2=28.280, P<0.001). The sensitivity rates of five antibiotics against ß-Lac isolates from the anterior segment were both statistically significant differences (χ2=50.971, 24.543, 48.147, 44.899, 18.676; all P<0.001). The susceptibility rates of ß-Lac isolates against five antibiotics was statistically significant differences (χ2=23.383, P<0.001). The sensitivity of cefazolin sodium and fusidic acid against ß-Lac isolates were higher than MRS isolates. Conclusions: Cefazolin sodium and fusidic acid may be the best choice for the treatment of drug-resistant Staphylococcus isolated from anterior conjunctival sac, cornea, eyelid margin and lacrimal sac, especially for ß-Lac-producing drug-resistant Staphylococcus infection.

[AGT rs5051 gene polymorphism increases the risk of coronary heart disease in patients with non-alcoholic fatty liver disease in the Han Chinese population].

Objective: To investigate the relationship between the angiotensinogen (AGT) rs5051 single nucleotide polymorphism (SNP) and the onset risk of coronary heart disease (CHD) in patients with non-alcoholic fatty liver disease (NAFLD) in the Han Chinese population. Methods: A total of 454 subjects were enrolled in this study. Among them, 140 cases were with NAFLD, 112 cases with NAFLD combined with CHD, and 202 healthy controls. Blood samples of all subjects were examined for biochemical indexes. Genotype at AGT rs5051 locus was detected by polymerase chain reaction. SPSS 21.0 statistical software was used for data statistical analysis. Results: The differences in distribution of AGT rs5051 genotypes and alleles between the NAFLD and the control group were not statistically significant (P > 0.05). The differences in the distribution of AGT rs5051 genotypes and alleles between the NAFLD combined with CHD and the NAFLD group were statistically significant (χ(2) = 10.32, P = 0.001; χ(2) = 11.72, P < 0.001). Binary logistic regression analysis results showed that TC + CC genotype had increased the occurrence risk of CHD in NAFLD patients (OR = 2.203, 95% CI: 1.322 ~ 3.670, P = 0.02) than AGT rs5051 TT genotype carriers. After adjusting for gender, age, and body mass index, the TC + CC genotype still significantly increased the occurrence risk of CHD in NAFLD patients (OR = 2.378, 95% CI: 1.384 ~ 4.087, P = 0.02). In addition, AGT rs5051 C allele mutations had significantly increased the occurrence risk of CHD in patients with NAFLD (OR = 2.018 before adjustment, 95% CI: 1.345 ~ 3.027, P = 0.001; OR = 2.161, 95% CI: 1.406 ~ 3.322 after adjustment. P < 0.001). Conclusion: This study is the first to report the correlation between AGT rs5051 polymorphism and the occurrence risk of CHD in patients with NAFLD in Han Chinese population. AGT rs5051 polymorphism can significantly increase the risk of CHD in patients with NAFLD.

[Quantitative analysis of non-alcoholic fatty liver disease based on MRI proton density fat fraction in the coastal region of Qingdao].

Objective: To explore the clinical application value of MRI-PDFF on different liver segments for the evaluation of non-alcoholic fatty liver disease (NAFLD). Methods: 178 volunteers from March 2019 to February 2020 were included. PDFF values ​​of all nine segments of the liver were measured using CSE3.0T MRI scan. The obtained average value was used to represent the average liver fat content. PDFF values of each or combined liver segment were equally compared with the average value to observe the representativeness of fat content. Receiver operating characteristic curve was used to analyze the diagnostic performance of each liver segment, and the Youden index was used to calculate the cutoff value. Paired-sample t-test or non-parametric Kruskal-Wallis test were used to compare measurement data among groups. Results: 178 volunteers average liver fat content ranged from 0.89% to 42.61% with MRI-PDFF, and 71.35% (127/178) of the volunteers had PDFF > 5%. There was no significant difference between SIII, SIVb, SV, and SVIII liver segments when compared with the average value (P > 0.05). PDFF values ​​of SI, SII, and SIV a liver segments were all lower than the average value, while the PDFF values ​​of SVI and SVII liver segments were all higher than the average value (P ​​< 0.05). MRI-PDFF sensitivity value for diagnosing liver steatosis of nine liver segments was 85.8% ~ 94.5%, and the specificity was higher than 96.0%. Among them, the SV liver segment had the highest sensitivity (94.5%), and the corresponding optimal diagnostic threshold value was 5.13%. Compared with single and combined liver segment, the PDFF value of SII, SV, SVI combined liver segment had the highest diagnostic performance for fatty liver, with the sensitivity and specificity of 96.9%, and 100%, respectively, and the corresponding optimal diagnostic threshold value was 5.17%. Conclusion: Compared with single and other combined liver segments, MRI-PDFF values of SII, SV, and SVI combined liver segments have higher sensitivity and specificity for the diagnosis of NAFLD, and it can be used as the first choice for the determination of liver fat content with MRI.

Can elevated concentrations of ALT and AST predict the risk of 'recurrence' of COVID-19?

'Recurrence' of coronavirus disease 2019 (COVID-19) has triggered numerous discussions of scholars at home and abroad. A total of 44 recurrent cases of COVID-19 and 32 control cases admitted from 11 February to 29 March 2020 to Guanggu Campus of Tongji Hospital affiliated to Tongji Medical College Huazhong University of Science and Technology were enrolled in this study. All the 44 recurrent cases were classified as mild to moderate when the patients were admitted for the second time. The gender and mean age in both cases (recurrent and control) were similar. At least one concomitant disease was observed in 52.27% recurrent cases and 34.38% control cases. The most prevalent comorbidity among them was hypertension. Fever and cough being the most prevalent clinical symptoms in both cases. On comparing both the cases, recurrent cases had markedly elevated concentrations of alanine aminotransferase (ALT) (P = 0.020) and aspartate aminotransferase (AST) (P = 0.007). Moreover, subgroup analysis showed mild to moderate abnormal concentrations of ALT and AST in recurrent cases. The elevated concentrations of ALT and AST may be recognised as predictive markers for the risk of 'recurrence' of COVID-19, which may provide insights into the prevention and control of COVID-19 in the future.

LINC00662 promotes glycolysis and cell survival by regulating miR- 375/HIF-1α axis in ovarian cancer.

Ovarian cancer (OC) is one of the most common gynecological malignancies, with the highest mortality rate in women worldwide. LINC00662, a long non-coding RNA (lncRNA), was shown to play a vital role in many malignancies, while little is known about its role in OC. Firstly, our study determined the expression of LINC00662 in OC tissues and cells. Upregulation or downregulation of LINC00662 were performed in OC cells to explore its effects on cell proliferation and glycolysis of OC. The interaction between LINC00662 and miR-375 was verified using luciferase assays and RNA immunoprecipitation. Results showed that LINC00662 was highly expressed in OC tissues and cells, and patients with increased expression of LINC00662 were associated with shorter overall survival. Furthermore, functional assays proved that LINC00662 was essential for OC cell proliferation and glycolysis. Subsequently, our study further revealed that LINC00662 acted as a competitive RNA and it could modulate the expression of HIF-1α through directly binding with miR- 375. Collectively, upregulation of LINC00662 in ovarian cancer tissues is closely correlated to poor survival. LINC00662 might regulate HIF-1α expression via miR-375. These findings suggested that LINC00662 has the potential to be explored as a diagnostic biomarker for OC.

[Molecular epidemiological characterization of group A rotavirus in domestic sewage in Jinan from 2016 to 2018].

Objective: To understand the detection of group A rotavirus (RVA) in domestic sewage and its molecular epidemiological characteristics, and further explore the feasibility and necessity of RVA environmental surveillance. Methods: From 2016 to 2018, we collected domestic sewage samples monthly in Jinan city, and concentrated them via anion membrane adsorption-elution method. Then RNA extraction and RVA VP7 and VP4 coding region RT-PCR amplification were performed. After purification, TA cloning and sequencing, homology analysis and phylogenetic analysis were conducted on the obtained sequences. Results: RVA G gene was detected in 31 of the 36 sewage samples (86.1% detection rate); RVA P genotype was detected in 33 samples (91.7% detection rate). A total of 536 RVA sequences were obtained, of which 225 G-type sequences belonged to 6 genotypes, and the G9 accounted for 92.4% (208/225); 311 P-type sequences were obtained, which belonged to 4 genotypes. The dominant P[8] accounted for 50.1% (156/311), followed by P[4] with 41.8% (130/311). Phylogenetic analysis shows that there were multiple transmission chains circulating in the dominant genotypes G9 and P[8]. Conclusion: The genotype, homology, and phylogenetic characteristics of sequences obtained from domestic sewage in Jinan area were described, which further confirmeing that RVA environmental surveillance is not feasible but also necessary.