[Drug resistance and genomic characteristics of a strain of O139 Vibrio cholerae isolated from human bloodstream infection].

Objective: To analyze the drug resistance and genomic characteristics of a strain of serogroup O139 Vibrio cholerae producing cholera toxin isolated from the bloodstream of a person with bacteremia. Methods: The broth dilution method and automatic drug sensitivity analyzer were used to determine the antibiotic sensitivity of the strain. The complete genome sequence of the strain was obtained by using second-generation gene sequencing and nanopore sequencing. BLAST software was used for comparison and analysis with CARD, Resfinder, ISfinder, VFDB, and other databases. The drug-resistant genes, insertion sequences and virulence genes carried by the strain were identified. MEGA 5.1 software was used to construct a genetic phylogenetic tree based on the core genomic single nucleotide polymorphisms. Results: V. cholerae SH400, as the toxigenic strain, carried multiple virulence-related genes and four virulence islands. The strain was resistant to streptomycin, tetracycline and cotrimoxazole, carrying corresponding drug-resistant genes. The strain also carried IncA/C plasmid with the size of 172914 bp and contained 10 drug-resistant genes. Combined with the genomic evolutionary relationship, this study found that the drug-resistant genes and drug-resistant plasmids carried among strains showed certain aggregation. The traditional ST type of strain SH400 was ST69, and the cgMLST type was a new type highly similar to cgST-252. Conclusion: This strain of serogroup O139 V. cholerae carries the ctxAB gene, multiple drug-resistant genes and IncA/C plasmid, and there are multiple drug-resistant islands.

[Long-term prevention and control effects of orthokeratology lenses designed for small treatment zones on children and adolescents with myopia].

Objective: To explore the characteristics of orthokeratology lenses designed for small correction zones and their effectiveness and safety in long-term prevention and control of myopia in children and adolescents. Methods: It was a prospective cohort study that included myopic children and adolescents who received corneal reshaping treatment at the Qingdao Eye Hospital of Shandong First Medical University between January 2019 and May 2020. The patients were randomly divided into two groups using computer-generated randomization, and were fitted with corneal reshaping lenses with small treatment zones and conventional designs, respectively. The uncorrected visual acuity, best-corrected visual acuity, refractive error, and axial length were measured before and after 6, 12, and 18 months of wearing the lenses. Corneal topography with the Pentacam was also performed, and the area and diameter of the corneal treatment zone were calculated using the Matlab software. Results: A total of 60 myopic patients (60 eyes) were enrolled, including 29 males and 31 females, with an age of (10.40±1.01) years and a spherical equivalent of (-2.88±0.42) D. There were 30 cases in the small correction zone group and 30 cases in the conventional group. There was no significant difference in uncorrected visual acuity and spherical equivalent between the two groups at each time point after treatment. The axial growth in the conventional group was (0.16±0.09) mm at 6 months after treatment, (0.28±0.17) mm at 12 months, and (0.37±0.20) mm at 18 months, whereas in the small treatment zone group it was (0.06±0.05) mm, (0.12±0.10) mm, and (0.18±0.14) mm, respectively. The myopia progression rate in the small treatment zone group was only 37.50%, 42.86%, and 48.64% of the conventional group at 6, 12, and 18 months, respectively. Corneal topography showed that the treatment area in the conventional group was (6.98±0.89) mm², while in the small treatment zone group it decreased by 23.2% [(5.36±0.73) mm²] (P<0.05). Correlation analysis revealed that the axial increase after 18 months of lens wearing was negatively correlated with the age before lens wearing (P<0.05), positively correlated with the corneal surface treatment zone size (P<0.05), and not correlated with the pupil diameter and spherical equivalent (all P>0.05). After the shaping treatment, the rate of adverse reaction, which was mild, in both groups was 10%, and the symptoms disappeared. Conclusion: Orthokeratology lenses with smaller treatment zones can significantly reduce the rate of axial length growth in children and adolescents compared to lenses with conventional treatment zones, without compromising treatment safety.

[A multi-center, randomized controlled study on the effect of Saccharomyces boulardii combined with triple therapy for the initial eradication of Helicobacter pylori infection].

Objective: To assess the efficacy and safety of Saccharomyces boulardii (S. boulardii) in combination with triple therapy as a first-line regimen for the eradication of Helicobacter pylori (H. pylori) in non-ulcer dyspepsia (NUD) patients. Methods: A total of 497 Helicobacter pylori-positive patients who underwent gastroscopy and diagnosed with NUD were enrolled from June 2018 to January 2020 in 9 medical centers across China. Participants were segmentedly randomly divided into 3 groups. Patients in group A received S. boulardii for 14 days and triple therapy for 10 days, while patients in group B received bismuth quadruple group for 10 days, and patients in group C received triple therapy for 10 days. The H. pylori status was determined by the 13C-urea breath test on the 44th day of the treatment. Symptom improvement and adverse reactions were assessed on the 14th and 44th day. Results: There were 229 males and 268 females in all 497 patients enrolled. They were aged 18-69 (46.1±11.8) years and 472 of them (158 cases in group A, 159 cases in group B, and 155 cases in group C) completed the trial. The intention-to-treat (ITT) eradication rates in patients in patients A, B and C were 77.8% (126/162), 80.1% (137/171) and 65.2% (107/164) respectively, and per protocol-based (PP) eradication rates were 79.7% (126/158), 86.2% (137/159) and 69.0% (107/155) respectively. The differences were statistically significant in ITT and PP analysis among 3 groups (ITT: χ²=11.14, P<0.01; PP: χ²=13.86, P<0.01). There was no significant difference between eradication rates of two quadruple therapys(all P>0.05), but both of them were significantly higher than that of standard triple therapy (both P<0.05). Statistics revealed that both quadruple therapys led to significantly higher symptom improvement of belching compared with that of standard triple therapy in day 14 (P<0.05). The relief of abdominal distension and belching symptom scores of group A were significantly higher than those of group C in day 44(all P<0.05). There was no serious adverse event reported. The incidence of diarrhea in group A was significantly lower than those in the other two groups (both P<0.05). Conclusions: The combination of S. boulardii and triple therapy can achieve a better eradication effect on H. pylori infection with NUD, and has advantages in symptom relief and safety.

[SMARCA4-deficient undifferentiated carcinoma of the gastrointestinal tract: a clinicopathological and immunohistochemical study of nine cases].

Objective: To investigate the clinicopathological features, immunophenotype and differential diagnoses of SMARCA4-deificient undifferentiated carcinoma (SMARCA4-DUC) of the gastrointestinal tract. Methods: The clinicopathological data and immunohistochemical profiles of nine cases of SMARCA4-DUC of the gastrointestinal tract diagnosed in Fudan University Shanghai Cancer Center, from 2018 to 2021, were analyzed retrospectively. The relevant literature was reviewed. Results: There were seven males and two females with age at presentation ranging from 39 to 74 years (mean 58 years, median 64 years). The tumor occurred in the stomach (6 cases), right hemicolon (2 cases) and duodenum (1 case). The main symptoms included dysphagia, abdominal pain, diarrhea and melena. Five cases were resected, and the tumor sizes ranged from 5.0 to 8.7 cm (mean 6.7 cm). Microscopically, the tumor was composed of sheets of undifferentiated round to epithelioid cells with large vesicular nuclei harboring prominent nucleoli and displaying brisk mitotic activity. Foci of dyscohesive rhabdoid cells were also noted. The tumor cells were generally uniform; however, prominent pleomorphism and spindle cell component was present in one case each. Five cases contained areas of coagulative necrosis, and one case showed myxoid change of the stroma. By immunohistochemistry, eight cases showed complete loss of BRG1 (SMARCA4) and BRM (SMARCA2) expression. Whereas the expression of these two markers was lost in the epithelioid component of one case, it remained in the spindle cell component (mosaic pattern). Apart from one case with partial expression of pan-cytokeratin, all other eight cases showed either limited (<5%, n=5) or totally negative (n=3) staining of pan-cytokeratin. In addition, four cases also expressed CD34, SOX2 and SALL4. Six patients had follow-up data: four died of disease within 1 year. Conclusions: SMARCA4-DUC of the gastrointestinal tract represents a highly aggressive malignancy with poor outcome. Due to lack of cell-specific differentiation, it is not uncommonly misdiagnosed as a wide variety of poorly-differentiated or undifferentiated tumors. Increased recognition of this rare but distinctive entity not only facilitates the diagnosis and differential diagnosis, but also provides important therapeutic and prognostic information for the clinicians.

[The mid-term effect of corneal collagen cross-linking for progressive keratoconus and the changes in rigid gas permeable contact lens fitting parameters].

Objective: To investigate the effect of corneal collagen cross-linking (CXL) for progressive keratoconus and to evaluate changes in the parameters of rigid gas permeable contact lens (RGPCL) fitting after surgery. Methods: It was a prospective cohort study. Fifty-three eyes of 41 keratoconus patients received accelerated CXL in Qingdao Eye Hospital of Shandong First Medical University from May to December 2018. There were 31 males and 10 females, aged (20.46±4.15) years. According to the corneal thickness, de-epithelial CXL (33 eyes) or trans-epithelial CXL (20 eyes) was performed. The best spectacle-corrected visual acuity, refractive power and the thinnest corneal thickness at baseline and at 6 weeks were compared. Corneal topography was performed at baseline and at 6 weeks, 3, 6 and 12 months postoperatively. Rose K RGPCLs were used before and 6 weeks after surgery, and the fitting status was monitored until 12 months after surgery. The t test was performed to analyze the difference before and after the operation. Results: The best spectacle-corrected visual acuity, refractive power, and the thinnest corneal thickness were not significantly changed over 6 weeks of follow-up, but the Kf, Ks and Kmax values were significantly increased in all patients (all P<0.05). In the de-epithelial group, the Kmax values before the operation, at 3, 6 and 12 months after the operation were (55.00±5.51) diopters (D), (54.73±5.34) D, (54.58±6.15) D and (54.20±5.49) D, respectively, and the decrease at 12 months was significant [(0.80±2.05) D; t=2.25, P=0.001]. In the trans-epithelial group, the Kmax values were (59.43±8.98) D, (57.97±8.79) D, (58.19±8.37) D and (56.94±7.19) D at the four time points, respectively, and the decreases at 3, 6 and 12 months were all significant [(1.46±2.09) D, (1.25±1.82) D, (2.49±3.64) D; t=3.12, 3.06, 3.50; P=0.006, 0.006, 0.007]. The best RGPCL-corrected visual acuity, the diameter and the average diopters of RGPCLs showed no significant change in both groups. The RGPCL base curve decreased by 0.07 mm in the de-epithelial group and by 0.13 mm in the trans-epithelial group (both P<0.05). The design of edge lifting was used in 10 eyes postoperatively in the de-epithelial group compared with 8 eyes preoperatively, and in 4 eyes postopratively in the trans-epithelial group compared with 7 eyes preoperatively. The number of eyes using the toric peripheral design of the lens was increased to 3 compared with 2 preoperatively in the de-epithelial group and from 1 to 4 in the trans-epithelial group. The acceptance rate of RGPCL fitting in both groups increased at 6 and 12 months after surgery compared to 6 weeks after surgery. Conclusions: The corneal curvature became steep slightly at 6 weeks after CXL and gradually recovered and flattened. The Kmax in the trans-epithelial group decreased earlier and more than that in the de-epithelial group. The base curve of the RGPCLs was slightly reduced after 6 weeks, and the toric peripheral design was increasingly needed, but the requirement for the design of the lifted edge was different between the two groups. A good RGPCL fitting can be achieved within 1 year after CXL.

[Evaluation of two biomechanical stiffness indexes in the diagnosis of eratoconus and their changes after corneal collagen cross-linking surgery].

Objective: To evaluate the diagnostic efficacy of stress-strain index (SSI) for different stages or degrees of keratoconus and changes of SSI and stiffness parameter A1 (SPA1) after corneal collagen cross-linking (CXL) surgery. Methods: Cross-sectional study and retrospective case series study. Ninety-four patients (113 eyes) diagnosed as clinical keratoconus (CKC) in Qingdao Eye Hospital from July 2019 to August 2021 were enrolled in the CKC group, including 69 males and 25 females, aged (20.82±4.53) years, and further divided into subgroups of mild (35 patients, 36 eyes), moderate (36 patients, 40 eyes) and severe (33 patients, 37 eyes) CKC. Fifty-six unaffected eyes of monocular keratoconus patients were enrolled in the subclinical keratoconus (SKC) group. Ninety-one healthy subjects (91 eyes) were recruited as the control group. All subjects were examined by Pentacam topography and Corvis ST measurements to obtain mean keratometry, maximal keratometry, deformation amplitude (DA) ratio at 2 mm, integrated radius (IR), Ambrósio's relational thickness to the horizontal profile, corneal central thickness, SPA1 and SSI for comparison. Forty-eight CKC patients (65 eyes) underwent CXL surgery, and the above parameters were recorded before and 3, 6 and 12 months after operation. Data were analyzed by the ANOVA test, Kruskal-Wallis H test, paired sample test, receiver operating characteristic curves and Pearson correlation. Results: The value of SPA1 in the SKC group accounted for 85.53% (87.92±12.38 vs. 102.79±11.74; t=-6.614, P<0.001) compared with the control group, but the value of SSI had no difference in the two groups (t=0.105, P=0.916). The value of SPA1 in the CKC group accounted for 52.87% (54.35±14.70 vs. 102.79±11.74; t=25.985, P<0.001) compared with the control group. The value of SSI in the CKC group accounted for 67.96% (0.70±0.14 vs. 1.03±0.14; t=-15.305, P<0.001) compared with the control group. The more severe the disease was, the smaller the SPA1 and SSI values were 64.27±12.12, 55.22±12.23, 43.75±12.33; 0.78±0.14, 0.71±0.11, 0.61±0.09, and there were significant statistical differences among groups (mild vs. moderate, mild vs. severe, moderate vs. severe; SPA1: t=3.257, -7.249, -4.159; all P<0.001. SSI: t=2.383, 5.065, 2.798; P=0.018,<0.001,=0.006). Receiver operating characteristic analysis showed that SPA1 had good diagnostic efficiency for subclinical patients [area under curve (AUC)=0.802], while the SSI had no diagnostic value (P=0.802). SPA1 had better diagnostic efficiency than the SSI for keratoconus in different stages, especially in the mild CKC and SKC groups (AUC: 0.914 vs. 0.847). The SSI had a significant positive correlation with SPA1 and a significant negative correlation with DA ratio and IR in the control, SKC and CKC groups (r=0.278, 0.368, 0.550; r=-0.346, -0.462, -0.547; r=-0.612, -0.591, -0.718; P<0.01). For patients who received CXL, maximal keratometry decreased significantly at 6 and 12 months postoperatively (t=4.029, 3.633; all P<0.001), whereas SPA1 increased significantly (t=-3.960, -4.500; all P<0.001). However, the SSI only increased significantly at 3 months (t=-2.577, P=0.012) and returned to the preoperative level at 6 and 12 months postoperatively, with no statistical difference compared with the preoperative level (t=-0.544, -0.257; P=0.589, 0.798). Conclusions: While there was no significant change in the SSI of SKC, the SSI of CKC decreased, and the more severe the disease was, the smaller the value was. The SSI was significantly and consistently correlated with DA ratio, IR and SPA1. The SSI compared with SPA1 had a lower degree of identification in different stages and degrees of keratoconus. The consistency of SPA1 with clinical effects after CXL surgery was higher than that of the SSI parameter.

[Genomic subtyping of nosocomial transmission of carbapenem resistant Klebsiella pneumoniae].

Objective: To analyze the genomic epidemiological subtyping of carbapenem resistant Klebsiella pneumoniae (CRKP) isolated from a Third-class A hospital in Zhengzhou. Methods: From December 4, 2019 to January 10, 2020, 67 strains of CRKP were isolated from the samples submitted by the clinical departments of a Third-class A teaching hospital in Zhengzhou for microbiological testing. Multi-locus sequence typing (MLST) and carbapenem resistance genes were identified by whole genome sequencing and sequence analysis. Based on the whole genome SNP, the phylogenetic tree was constructed, and 67 CRKP strains were divided into clonal groups. The isolation ward and date of each clone group were analyzed. Results: Sixty-seven CRKP strains were classified into four MLST types (STs), of which 64 were ST11. There were 62 ST11 strains carrying blaKPC-2 gene. Based on genome-wide SNP phylogenetic tree, 64 ST11 strains were divided into four clone groups, two of which were dominant clone groups, including 33 and 27 strains respectively; the other two clone groups only contained 2 strains respectively. There was no aggregation of the dominant clones in the isolation department and date. Conclusion: Multiple clonal groups of ST11 strain carrying blaKPC-2 gene are differentiated during spreading, and they can spread in parallel and independently in the same hospital.

[Superficial CD34-positive fibroblastic tumor: a clinicopathological analysis of 25 cases].

Objective: To investigate the clinicopathological features and immunophenotype of superficial CD34-positive fibroblastic tumor (SCDFT) with an emphasis on differential diagnosis. Methods: The clinicopathological data and immunohistochemical profiles of 25 cases of SCPFT diagnosed from March 2015 to June 2020 in Department of Pathology, Fudan University Shanghai Cancer Center, China were analyzed. The literature was reviewed. Results: There were 14 males and 11 females, with the age at presentation ranging from 16 to 60 years (mean 38 years; median 40 years). Tumor occurred in the thigh (n=9), buttock (n=4), upper arm (n=3), shoulder (n=2), waist (n=2), lower leg (n=2), chest wall (n=1), abdominal wall (n=1) and vulva (n=1). Most of the patients presented with a slowly growing cutaneous nodule, with a mean diameter of 2.6 cm (range 1-5 cm). The duration of symptoms ranged from 1 week to 30 years. Microscopically, most of the tumors were located in the deep dermis to superficial subcutis. They were well circumscribed but frequently showed focal infiltration into adjacent adipose tissue. Tumor cells were composed of fascicles and sheets of spindled to polygonal cells with abundant eosinophilic cytoplasm possessing frequent granular or glassy appearance. Lipidized cells were also present. The striking feature was the presence of hyperchromatic pleomorphic cells, containing conspicuous nucleoli and intranuclear pseudoinclusion. Mitotic activity was very low. Besides, there were inflammatory infiltrates in the stroma. All tumors showed strong and diffuse immunohistochemical staining of CD34, with frequent focal expression of CKpan and occasional immunoreactivity of desmin. Follow-up data, which were available in 18 patients (range 7 to 69 months), showed a local recurrence in one patient and disease-free in all others. Conclusions: SCPFT is a newly-recognized low-grade fibroblastic tumor. Due to the marked nuclear pleomorphism, it is not uncommon to misdiagnose SCPFT as other pleomorphic mesenchymal tumors. Familiarity with its clinicopathological characteristics is helpful in avoiding overdiagnosis and overtreatment.

[Clinicopathological features of primary central nervous system T-cell lymphomas].

Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of primary central nervous system T-cell lymphomas (TPCNSL), and to analyze its biological behavior and prognosis. Methods: Three cases of TPCNSL were collected from September 2014 to September 2019 in the First Affiliated Hospital of Nanjing Medical University. They were evaluated by HE, immunohistochemistry (IHC) and molecular genetics, and the relevant literature was reviewed. Results: Among the 6 816 brain tumors, 97 were primary central nervous system lymphomas (PCNSL), including 3 TPCNSL. There were two male and one female patients, aged 60, 67, and 82 years. Clinically, they were presented with varying degrees of limb numbness and unstable gait. Microscopically, the tumor cells were distributed diffusely or around blood vessels. They showed significant atypia and brisk mitotic activity. By IHC, they were positive for LCA, CD3, CD43, TIA-1, and perforin. Two of three cases were positive for CD5 and granzyme B. T-cell receptor gene rearrangement was clonal. EBER in situ hybridization was negative. The patients were followed for 1 to 6 months; one patient received chemotherapy and died of recurrence 3 months after surgery. One patient died of recurrence 5 months after operation alone. One patient remained recurrence and metastasis free more than 4 months post surgery. Conclusions: PCNSL is uncommon, and most are B-cell lymphomas, while T-cell lymphomas are even rarer. As the latter may show atypical clinical manifestations, diverse histologic morphology and poor prognosis, early diagnosis and timely treatment are particularly important for patients to improve survival.

[Bronchiolar adenoma: a clinicopathological analysis of 15 cases].

Objective: To study the clinicopathological characteristics, diagnosis and differential diagnosis of bronchiolar adenoma (BA). Methods: Fifteen cases of BA were collected from the First Affiliated Hospital of Nanjing Medical University, from January 2016 to October 2019. The clinical data, imaging examination, morphology, immunostaining and molecular changes were retrospectively analyzed. Results: There were 3 males, 12 females, most of the patients were female, mainly in middle-aged to elderly (51-77 years). Three had smoking history. The patients usually had no clinical symptoms. Imaging findings were ground-glass and/or lobulated nodules. Grossly, the tumors were gray-whitish, taupe solid or focally microcystic nodules with distinct boundary but no capsule. The maximum diameter was 0.4-2.5 cm (mean 1.0 cm). Histologically, there were glandular, papillary, or flat patterns that were composed of basal cells, mucous cells, ciliated cells and type Ⅱ pneumocytes, some of which showed basal cell proliferation and squamous cell metaplasia. However, there were some cases with few or even without mucous and/or ciliated cells. Immunostaining highlighted the continuous basal cell layer (positive for p63, p40 and cytokeratin 5/6), which was the most important diagnostic evidence. Genetic tests did not show mutation in BRAF or EGFR genes. All patients were followed up for 1-41 months, and they were without recurrence or metastasis. Conclusions: BA is a benign neoplasm that develops in the peripheral lung with good prognosis. Definite diagnosis is very crucial for surgical treatment, especially in frozen consultation. Immunohistochemistry will be helpful if necessary.

[Characteristics of corneal topography in parents of keratoconus patients].

Objective: To investigate the corneal topographic characteristics of the parents of patients with keratoconus (KC) and the correlation with their offspring. Methods: Case-control study. Twenty-six patients (49 eyes) with KC, who were 15 males and 11 females, and (18.83±2.74) years old, 48 parents (96 eyes) of patients with KC, who were 23 males and 25 females, and (44.14±1.70) years old, and 44 controls (88 eyes), who were 22 males and 22 females, and (42.81±4.03) years old, were enrolled in Qingdao Eye Hospital. The indexes in the Belin/Ambrósio Enhanced Ectasia Display were acquired with Pentacam topography. The basic indicators were flat K/steep K/maximum K (Kmax) curvature and astigmatism, thinnest pachymetry (TP), and front/back elevation (Ef/Eb); the Belin indexes included deviation of normality of the front/back elevation (Df/Db), deviation of average pachymetry progression/normality of corneal thinnest point/normality of relational thickness (Dp/Dt/Da), overall deviation of normality (Do), minimum/maximum/average pachymetric progression indices (PPImin/PPImax/PPIave), and Ambrósio's average and maximum relational thickness indices (ARTave/ARTmax). All parameters in the groups of parents and controls were compared by Mann-Whitney U test. The ROC curve was used to analyze the differential value of each abnormal index. In addition, the ratio of abnormal indicators in the Belin/Ambrósio Enhanced Ectasia Display was statistically analyzed. Partial correlation analysis was used to find the correlation between the parameters of KC patients and their parents, and binary logistics regression analysis was used to predict the prevalence in children through the parental indicators. Results: Clinical KC was diagnosed in 1 of the 48 parents (2.08%) of patients with KC. There was no statistically significant difference in anterior surface parameters such as K1, K2, Kmax, astigmatism and Ef, but differences in the thickness [522.00 (493.00, 542.75) µm versus 540.00 (523.25, 559.50) µm] and posterior surface elevation value [8.00 (4.00, 11.00) µm versus 5.00 (3.00, 8.00) µm] were statistically significant. Except for Df, the other Belin/Ambrósio indicators such as Do (Z=-4.551, P=0.000), PPImax (Z=-3.959, P=0.000) and ARTave (Z=-4.792, P=0.000) indicated significant difference. The ROC curve analyses showed ARTave had the greatest value in the identification of KC patients (AUC=0.705), PPImax had the best sensitivity (0.845), and Eb had the best specificity (0.837). The ratio of suspicious indicators between the parents' group and the control group was 1.5∶1, and the ratio of pathological indicators was 3∶1. There was a correlation in multiple parameters between KC patients and their parents (all P>0.05). Do/Eb/TP indices of mothers and Do/Kmax indices of fathers were the major influence factors for the disease in the offspring, with a diagnosis rate of 85.6%. Conclusions: The corneal topographic map of the parents of patients with KC showed that the index of the anterior surface was normal, but the thickness was thinner and the posterior surface was higher. According to Belin's analysis, all indicators except Df were abnormal. Moreover, the ratio of suspected and pathological indicators increased. These data suggested that the corneal topography of parents of patients with KC had features of subclinical KC. Compared with the traditional index, ARTave was of the highest value in the identification of subclinical KC. There was a strong correlation between parents of patients with KC and offspring. The Do and Kmax indices of paternal parents and the Do, Eb and TP indices of maternal parents were good predictors of children's disease. (Chin J Ophthalmol, 2020, 56:456-464).

[The changes in corneal transparency after orthokeratology with juvenile myopia].

Objective: To evaluate the changes of corneal transparency undergoing overnight orthokeratology treatment. Methods: Prospective cohort study. Right eyes of juvenile myopic patients fitted with Ortho-K CL at Qingdao Eye Hospital were enrolled. Corneal optical density values were measured by the Pentacam Scheimpflug system before orthokeratology and at 1 day, 1 week, and 1, 3, 6, and 12 months after wearing. Four concentric radial zones centered on the apex of the cornea (≤2 mm, >2 mm and ≤6 mm, >6 mm and ≤10 mm, and>10 mm and ≤12 mm diameter) were applied. Anterior layer (anterior 120 µm), central layer, and posterior layer (posterior 60 µm) were defined according to corneal depth. The data analysis were used One-Way Repeated Measures ANOVA and LSD test. Results: Forty patients (40 eyes) with myopia (24 male and 16 female, age 10.76±1.74 years) were in enrolled. Corneal optical density value was 13.18±0.23 before orthokeratology, then showed a decreasing trend at the early stage, but there was no statistical difference (within 3months: t=-1.594, -1.472, 0.064, 1.971; P>0.05). The value increased significantly and reached the peak (15.31±0.23, t=7.613, P<0.01) at 6-month, and was still maintained in a high value at 1-year (15.15±0.24, t=7.227, P<0.01). Anterior, central, and posterior layer of corneal optical density values had a downward trend at early stage, and increased significantly in 6-and 12-month (anterior layer t=7.143, 6.177, central layer t=7.508, 6.563, posterior layer t=6.722, 8.533;P<0.01). Only the values decreased significantly in posterior layer at 1-week (baseline 10.21±0.14 vs. 1-week 9.91±0.14, t=-2.348, P=0.024). The corneal optical density value of ≤2 mm diameter began to increase significantly at 1-month (baseline 12.88±0.14 vs. 1-month 13.31±0.19, t=2.158, P=0.037),>2 mm and ≤6 mm diameter at 3-month (baseline 11.71±0.13 vs. 3-month 12.50±0.19, t=3.213, P=0.003), and>6 mm and ≤10 mm diameter at 6-month (baseline 11.40±0.30 vs. 6-month 13.70±0.33, t=7.635, P=0.000). The high values lasted for 1 year at this three areas. However, >10 mm and ≤12 mm diameter had no obvious change in optical density (F=1.668, P>0.05). In addition, the significant reduction of optical density values at early stage were mainly concentrated in the posterior layer of the cornea and the>6 mm and ≤10 mm diameter. Conclusions: Orthokeratology transiently increases corneal transparency of the posterior layer and the>6 mm and ≤10 mm diameter at early stage. However, long-term wearing can cause a decrease of transparency within a 10 mm diameter range. The corneal transparency changes first at the center of the optical zone, then gradually expanding to the periphery, and the anterior, central and posterior layers of cornea are all affected. We speculate orthokeratology affect the corneal oxygen supply and compress cornea mechanically, that leads to corneal stromal remodeling. (Chin J Ophthalmol, 2019, 55:435-441).

Cartilage-specific deletion of Alk5 gene results in a progressive osteoarthritis-like phenotype in mice.

OBJECTIVE: Previous studies have shown that Transforming growth factor-ß (TGF-ß)/TGFßRII-Smad3 signaling is involved in articular cartilage homeostasis. However, the role of TGF-ß/ALK5 signaling in articular cartilage homeostasis has not been fully defined. In this study, a combination of in vitro and in vivo approaches was used to elucidate the role of ALK5 signaling in articular cartilage homeostasis and the development of osteoarthritis (OA). DESIGN: Mice with inducible cartilage-specific deletion of Alk5 were generated to assess the role of ALK5 in OA development. Alterations in cartilage structure were evaluated histologically. The expressions of genes associated with articular cartilage homeostasis and TGF-ß signaling were analyzed by qRT-PCR, western blotting and immunohistochemistry. The chondrocyte apoptosis was detected by TUNEL staining and immunohistochemistry. In addition, the molecular mechanism underlying the effects of TGF-ß/ALK5 signaling on articular cartilage homeostasis was explored by analyzing the TGF-ß/ALK5 signaling-induced expression of proteoglycan 4 (PRG4) using specific inhibitors. RESULTS: Postnatal cartilage-specific deletion of Alk5 induced an OA-like phenotype with degradation of articular cartilage, synovial hyperplasia, osteophyte formation, subchondral sclerosis, as well as enhanced chondrocyte apoptosis, overproduction of catabolic factors, and decreased expressions of anabolic factors in chondrocytes. In addition, the expressions of PRG4 mRNA and protein were decreased in Alk5 conditional knockout mice. Furthermore, our results showed, for the first time, that TGF-ß/ALK5 signaling regulated PRG4 expression partially through the protein kinase A (PKA)-CREB signaling pathway. CONCLUSIONS: TGF-ß/ALK5 signaling maintains articular cartilage homeostasis, in part, by upregulating PRG4 expression through the PKA-CREB signaling pathway in articular chondrocytes.

MNS, Duffy, and Kell blood groups among the Uygur population of Xinjiang, China.

Human blood groups are a significant resource for patients, leading to a fierce international competition in the screening of rare blood groups. Some rare blood group screening programs have been implemented in western countries and Japan, but not particularly in China. Recently, the genetic background of ABO and Rh blood groups for different ethnic groups or regions in China has been focused on increasingly. However, rare blood groups such as MN, Duffy, Kidd, MNS, and Diego are largely unexplored. No systematic reports exist concerning the polymorphisms and allele frequencies of rare blood groups in China's ethnic minorities such as Uygur and Kazak populations of Xinjiang, unlike those on the Han population. Therefore, this study aimed to investigate the allele frequencies of rare blood groups, namely, MNS, Duffy, Kell, Dombrock, Diego, Kidd, Scianna, Colton, and Lutheran in the Uygur population of Xinjiang Single specific primer-polymerase chain reaction was performed for genotyping and statistical analysis of 9 rare blood groups in 158 Uygur individuals. Allele frequencies were compared with distribution among other ethnic groups. Observed and expected values of genotype frequencies were compared using the chi-square test. Genotype frequencies obeyed the Hardy-Weinberg equilibrium (P > 0.5) and allele frequencies were stable. Of all subjects detected, 4 cases carried the rare phenotype S-s- of MNS blood group (frequency of 0.0253), and 1 case carried the phenotype Jka-b- (frequency of 0.0063). Frequencies of the four groups, MNS, Duffy, Dombrock, and Diego, in the Uygur population differed from those in other ethnic groups. Gene distribution of the Kell, Kidd, and Colton was similar to that in Tibetan and Han populations, though there were some discrepancies. Gene distribution of Scianna and Lutheran groups showed monomorphism similar to that in Tibetan and Han populations. These findings could contribute to the investigation of the origin, evolution, and hematology of Uygur population of Xinjiang and assist in screening of rare blood groups in ethnic minorities, meeting of clinical blood supply demands, and building of the national rare blood group library.

Lower Circulating Irisin Level in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Studies measuring circulating irisin levels in patients with insulin resistance conditions such as type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) have achieved controversial results. Our systematic review and meta-analysis aim to assess the circulating irisin levels in patients with diabetes mellitus. Pubmed, EMBASE, CENTRAL, ISI Web of Science, and CNKI were searched to identify observational studies of circulating irisin levels in patients with diabetes mellitus. Two reviewers independently searched the databases and screened studies according to the inclusion criteria. Data were extracted using a standardized collection form. Meta-analysis was performed. A total of 23 studies (17 cross-sectional and 6 case control) involving 1 745 diabetic patients and 1 337 non-diabetic controls were selected. Compared with non-diabetic controls, circulating irisin concentrations were significantly lower in patients with T2DM (SMD -1.72, 95%CI -2.49, -0.96; p<0.00001) and GDM (SMD -0.76, 95CI -1.31, -0.22; p=0.006), but 30 percent higher in patients with T1DM. Circulating irisin in Asian diabetic patients decreased more than European patients. The findings of our current review suggest that circulating irisin levels were decreased in patients with T2DM and GDM, but not in patients with T1DM.

Effect of OPCML gene on the biological behavior of gastric cancer cell line AGS.

The objective of this investigation was to explore the association of OPCML with gastric cancer and its clinical significance. The expression of OPCML was detected by immunohistochemistry in 118 cases of gastric carcinoma. The OPCML expression in the normal tissues and 7 kinds of gastric cells was assessed by RT-PCR. The recombinant plasmid pcDNA3.1-OPCML was constructed and transfected into AGS cells. CCK8 and colony formation assay were employed to analyze the effect of OPCML on AGS. Immunohistochemistry results showed that the expression of OPCML in gastric cancer was 68.6% and the expression of OPCML was negatively correlated with the depth of tumor invasion and tumor differentiation degree (P < 005); OPCML expression, depth of tumor invasion, lymph node metastasis and distant metastasis were important factors affecting the prognosis of the survival of the patients (P <0.05). OPCML m-RNA expression in the gastric cancer cells was significantly lower than that in the normal gastric mucosa. RT-PCR showed that the expression of OPCML was aberrantly increased in the cells transfected with pcDNA3.1-OPCML. CCK8 and colony formation assay showed that OPCML significantly inhibited the growth, proliferation, and colony formation of the AGS cells. OPCML plays an important role in gastric cancer, and may be a new prognostic indicator of gastric cancer.

Clinical observational study of conformal radiotherapy combined with topotecan chemotherapy in patients with platinum-resistant recurrent ovarian cancer.

This retrospective study aimed to observe the cura-tive effect and adverse reactions of three-dimensional conformal radiotherapy combined with topotecan chemotherapy in patients with platinum-resistant recurrent epithelial ovarian carcinoma. The chemoradiotherapy group (N = 22) received 15 mv X-rays with 1.8 to 2.0 Gy/f/d radiation, 5 times per week. The total dose was 45 to 65 Gy; the median dose was 52.5 Gy. Topotecan chemotherapy (2.0 mg/m(2)) was administered after the first week of radiotherapy on days 1, 8, and 15; it was repeated every 28 days. The only che-motherapy group (N = 20) received topotecan chemotherapy (4.0 mg/m(2)) in the first week, and the dose was administered on days 1, 8, and 15; it was repeated every 28 days. The median follow-up times were 18.5 months (2 to 37.7) and 10.8 months (1.5 to 29.6) in the chemoradiotherapy and in the only chemotherapy groups, respectively. The total response rates were 42.1% (8/19) and 11.1% (2/18), respectively. The clinical benefit rates were 68.4% (13/19) and 22.2% (4/18), respectively, with significant difference (P < 0.05). The median disease progression-free periods were 9.8 and 6.6 months, respectively, with significant difference (P < 0.001). The median survival times were 19.7 and 12.5 months, respective-ly, with significant difference (P < 0.05). The degrees of digestive tract reaction rates were 26.3% (5/19) and 16.7% (3/18), whereas the hematology toxicity rates were 21.1% (4/19) and 22.2% (4/18), respectively, with no significant difference (P > 0.05). As three-dimensional conformal radiotherapy combined with topotecan che-motherapy had good curative effect on platinum-resistant recurrent epithelial ovarian cancer, with mild adverse reactions, this tech-nique can be used as a remedial measure.

Effects of newly developed chemotherapy regimens, comorbidities, chemotherapy-related toxicities on the changing patterns of the leading causes of death in elderly patients with colorectal cancer.

BACKGROUND: Abundant evidences have shown that newly developed chemotherapy regimens improved 5-year survival rate of colorectal cancer (CRC) patients over the past two decades. However, their impact on risk of death from leading causes among elderly patients is still poorly understood. PATIENTS AND METHODS: A retrospective cohort study of 69 718 elderly CRC patients with their first primary tumors in 1992-2009, identified from the 12 areas of Surveillance, Epidemiology, and End Results-Medicare linked database with their Medicare claims up to 2010. Multivariate Cox regression models were used to assess the effect of newly developed chemotherapy regimens, comorbidities, and chemotherapy related toxicities on cause-specific death and their temporal patterns among elderly CRC patients. RESULTS: The leading causes of death among CRC patients were CRC, circulation disorders, and secondary cancers, which accounted for 51.4%, 25%, and 4.6% of all-cause death, respectively. Patients diagnosed in more recent diagnostic time periods were significantly less likely to die of CRC [period 2: 5-year hazard ratio = 0.94, 95% confidence interval (CI) 0.90-0.97; period 3: 0.86, 0.83-0.90], circulation disorders (period 2: 0.94, 0.88-1.00; period 3: 0.80, 0.75-0.87), and more likely to die of secondary cancer (period 3: 1.42, 1.20-1.68) compared with those diagnosed in period 1. Charlson comorbidities index and the selected pre-existing comorbidities were significantly associated with increased 5-year risk of death from all three leading causes. Both hematological and gastric toxicity were associated with reduced risk of death from CRC and circulation disorders. The association between diagnostic time period and risk reduction in death from CRC depended on chemotherapy treatment (P < 0.0001). Subgroup analyses showed that the chemotherapy-dependent significant risk reduction was seen in patients with stage II-III CRC, patients without comorbidities, and patients without toxicities (P < 0.0001 for all). CONCLUSION: The newly developed chemotherapy regimens were associated with the decreased risk of mortality from CRC.