Design, synthesis, and antifungal mechanism of carbaline fluorescent probes / 药学学报

Three carboline fluorescent probes F1-F3 were designed and synthesized, based on lead compound JYJ-19, an antifungal compound discovered previously by our group. The antifungal activity in vitro results showed that compound F1 had moderate antifungal activity (MIC80 = 32 μg·mL-1). The stokes shift of F1 is 70 nm. The fluorescent probe F1 has good optical properties and can be used for fluorescence imaging research. Subcellular localization experiments results showed that F1 was enriched in the mitochondria of fungal cells. The detection of intracellular reactive oxygen species levels shows that JYJ-19 enhances intracellular reactive oxygen species levels. The above results indicated that carboline compounds could exert antifungal effects by acting on fungal mitochondria.

Epidemiological characteristics of pertussis in Hubei Province in 2016 - 2021 / 公共卫生与预防医学

Objective To understand the epidemiological characteristics and current situation of pertussis in Hubei Province from 2016 to 2021. Methods Data on the incidence of pertussis and immunization history of cases in Hubei Province from 2016 to 2021 were collected and descriptive epidemiological analysis was conducted. Results From 2016 to 2021, a total of 1 236 pertussis cases were reported in Hubei Province, with an average annual reported incidence rate of 0.35/100 000. The average annual reported incidence of pertussis in the age group ≤ 5 years old was 6.22/100 000, and the age group <1 year old reported the highest annual incidence rate (21.51/100 000). The proportion of pertussis among preschool children and students had increased significantly since 2020. Among the 1 111 cases with a known immunization history, 17.55% were under the age of vaccination , 41.85% were not vaccinated, and 17.46% had completed the whole course of vaccination. Conclusion Since 2016, the incidence of pertussis in Hubei Province has been on the rise. The risk of pertussis is higher in infants and young children who have not reached the age of vaccination and who have not been vaccinated in time according to the immunization program after reaching the age of vaccination. The timeliness and vaccination rate of DTP vaccine should be improved to reduce the risk of pertussis in infants and young children. In addition, more attention should be paid to the prevalence of pertussis among preschool children and students.

Treatment duration of wrist-ankle acupuncture for relieving post-thyroidectomy pain: A randomized controlled trial / 中西医结合学报

BACKGROUND@#Treatment duration of wrist-ankle acupuncture (WAA) is uncertain for post-thyroidectomy pain relief.@*OBJECTIVE@#This study evaluated the effect of different WAA treatment duration on post-operative pain relief and other discomforts associated with thyroidectomy.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This randomized controlled trial was conducted at a single research site in Guangzhou, China. A total of 132 patients receiving thyroidectomy were randomly divided into the control group (sham WAA, 30 min) and three intervention groups (group 1: WAA, 30 min; group 2: WAA, 45 min; group 3: WAA, 60 min), with group allocation ratio of 1:1:1:1. Acupuncture was administered within 1 hour of leaving the operating room.@*OUTCOMES AND MEASURES@#Primary outcome was patients' pain at the surgical site assessed by visual analogue scale (VAS) at the moment after acupuncture treatment (post-intervention). Secondary outcomes included the patients' pain VAS scores at 6, 12, 24, 48 and 72 h after the thyroidectomy, the 40-item Quality of Recovery (QoR-40) score, the grade of post-operative nausea and vomiting (PONV), and the use of additional analgesic therapy.@*RESULTS@#The adjusted mean difference (AMD) in VAS scores from baseline to post-intervention in group 1 was -0.89 (95% confidence interval [CI], -1.02 to -0.76). The decrease in VAS score at post-intervention was statistically significant in group 1 compared to the control group (AMD, -0.43; 95% CI, -0.58 to -0.28; P < 0.001), and in groups 2 and 3 compared to group 1 (group 2 vs group 1: AMD, -0.65; 95% CI, -0.81 to -0.48; P < 0.001; group 3 vs group 1: AMD, -0.66; 95% CI, -0.86 to -0.47; P < 0.001). The VAS scores in the four groups converged beyond 24 h after the operation. Fewer patients in group 2 and group 3 experienced PONV in the first 24 h after operation. No statistical differences were measured in QoR-40 score and the number of patients with additional analgesic therapy.@*CONCLUSION@#Compared with the 30 min intervention, WAA treatment with longer needle retention time (45 or 60 min) had an advantage in pain relief within 6 h after surgery. WAA's analgesic effect lasted for 6-12 h post-operatively. Please cite this article as: Han XR, Yue W, Chen HC, He W, Luo JH, Chen SX, Liu N, Yang M. Treatment duration of wrist-ankle acupuncture for relieving post-thyroidectomy pain: A randomized controlled trial. J Integr Med. 2023; 21(2): 168-175.

Genetic analysis of a pregnant woman with moderate intellectual disability due to variant of DLG4 gene / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing and prenatal diagnosis for a woman featuring moderate intellectual disability (ID).@*METHODS@#The patient had presented at the First Affiliated Hospital of Zhengzhou University on April 28, 2021. With informed consent, peripheral blood and amniotic fluid samples were collected for the extraction of genomic DNA. Pathogenic copy number variations (CNVs) were detected with CNV-seq, and single gene variants were detected by whole exome sequencing (WES) and Sanger sequencing. Candidate variant was verified by Sanger sequencing, and CNV-seq and multiplex ligation-dependent probe amplification (MLPA) were used to detect fetal CNVs.@*RESULTS@#The 23-year-old woman had moderate ID, sideway walking, and unstable holding. Ultrasonography at 18+3 weeks' gestation had revealed no fetal abnormality. No pathogenic CNV was detected in the woman by CNV-Seq, while WES revealed that she has harbored a heterozygous c.1675C>T (p.Arg559*) variant of the DLG4 gene, which was verified by Sanger sequencing. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PVS1+PM2_supporting). Sanger sequencing has confirmed that the fetus has inherited this variant, and CNV-Seq also revealed that that fetus has harbored a 0.1 Mb heterozygous deletion at Xp21.1, which has encompassed the DMD gene, and the result was verified by MLPA.@*CONCLUSION@#The heterozygous c.1675C>T variant of the DLG4 gene probably underlay the mental retardation in this woman, and her fetus was found to harbor the same variant in addition with deletion of the DMD gene, which may predispose to ID type 62.

Characteristics of serum bile acids among healthy children in Zhejiang province / 中华儿科杂志

Objective: To characterize the serum bile acid profiles of healthy children in Zhejiang Province. Methods: A cross-sectional study was conducted on 245 healthy children who underwent imaging and laboratory biochemical tests during routine physical examinations at the Children's Hospital of Zhejiang University School of Medicine from January 2020 to July 2022. Overnight fasting venous blood samples were collected, and the concentrations of 18 individual bile acids in the serum were accurately quantitated using tandem mass spectrometry. The concentration difference of bile acid were compared between different genders and to explore the correlation between age and bile acid levels. Used the Mann-Whitney U test for intergroup comparison and Spearman test to correlation analysis. Results: A total of 245 health children with a age of 10 (8, 12) years including 125 boys and 120 girls. There were no significant differences in levels of total bile acids, primary and secondary bile acids, free and conjugated bile acids between the two gender groups (all P>0.05). The serum concentrations of ursodeoxycholic acid and glycoursodeoxycholic acid in girls were significantly higher than those in boys (199.0 (66.9, 276.5) vs. 154.7 (49.3, 205.0) nmol/L, 274.0 (64.8, 308.0) vs. 181.0 (43.8, 209.3) nmol/L, Z=2.06, 2.71, both P<0.05). The serum taurolithocholic acid in both boys and girls were positively correlated with age (r=0.31, 0.32, both P<0.05). The serum chenodeoxycholic acid and glycochenodeoxycholic acid in the boys group were positively correlated with age (r=0.20, 0.23, both P<0.05), whereas the serum tauroursodeoxycholic acid in the girls group was negatively correlated with age (r=-0.27, P<0.05), and the serum cholic acid was positively correlated with age (r=0.34, P<0.05). Conclusions: The total bile acid levels are relatively stable in healthy children in Zhejiang province. However, individual bile acids showed gender differences and were correlated with age.

Mechanism of Ethyl Acetate Extract of Gentianopsis paludosa in Treatment of Ulcerative Colitis Based on Bcl-2/Bax Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of ethyl acetate extract of Tibetan medicine dampness bud Gentianopsis paludosa in the prevention and treatment of recurrent ulcerative colitis （UC） in rats with dampness-heat in large intestine syndrome based on the apoptotic pathway mediated by the B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）. MethodUsing the disease-syndrome combination method， a recurrent UC model of dampness-heat in large intestine syndrome was constructed in rats. Seventy SPF-grade male SD rats were randomly divided into control group， model group， high-， medium-， and low-dose ethyl acetate of G.paludosa groups （150， 75， 37.5 mg·kg-1）， and mesalazine group （135 mg·kg-1）. The rats were orally administered with respective drugs for 14 days. The general conditions of the rats were recorded， and colon length and mucosal damage were observed. The colon wet weight index and organ coefficients of the liver， spleen， and thymus were calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-6 （IL-6） and interleukin-1β （IL-1β） in the serum of each group. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in the colon. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） was used to detect apoptosis in colonic epithelial cells. Western blot was used to measure the expression levels of Bcl-2， Bax， Caspase-3， Caspase-9， Zona Occludens-1 （ZO-1）， Claudin3， and Occludin in colonic tissue. Immunohistochemistry （IHC） was used to observe the expression of Bax and Caspase-3 in colonic epithelial cells. ResultCompared with the control group， the model group showed significant increases in the disease activity index （DAI） score， colonic mucosal damage index （CMDI）， intestinal epithelial apoptosis， liver and spleen indexes， and levels of inflammatory factors IL-1β and IL-6 in the serum （P<0.01）， decreased expression of intestinal mucosal protective proteins ZO-1， Claudin3， and Occluding （P<0.01）， increased expression of pro-apoptotic proteins Bax， Caspase-3， and Caspase-9 （P<0.01）， and decreased expression of anti-apoptotic protein Bcl-2 （P<0.01）. Compared with the model group， the high-， medium-， and low-dose ethyl acetate of G.paludosa groups all significantly improved the general condition of the rats， reduced colonic lesions， decreased intestinal epithelial cell apoptosis， reduced liver and spleen indexes， upregulated the expression of ZO-1， Claudin3， Occludin， and Bcl-2 proteins， and downregulated the expression of Bax， Caspase-3， and Caspase-9 proteins， with the high- and medium-dose ethyl acetate of G.paludosa groups showing the superior effects （P<0.05， P<0.01）. ConclusionEthyl acetate of G.paludosa can alleviate colonic mucosal damage and exert a therapeutic effect on UC by regulating the Bcl-2/Bax signaling pathway.

Real-world Efficacy and Safety Comparison of Neoadjuvant Treatment of HER2-positive Breast Cancer with TCbHP Versus AC-THP / 肿瘤防治研究

Objective To compare the efficacy, safety, and survivability of TCbHP versus AC-THP in the neoadjuvant therapy of HER2-positive breast cancer in real-world. Methods Clinical data of patients with HER2 positive breast cancer, who have received TCbHP or AC-THP as neoadjuvant therapy and completed surgery in 11 third-class hospitals in various cities of Hebei Province, were retrospectively collected.The total pathological complete remission (tpCR) rate, the incidence of grade 3 or higher adverse reactions and the completion rate of the given approaches were compared. Results A total of 110 cases were collected, including 78 cases in the TCbHP group and 32 cases in the AC-THP group.The tpCR rate of the TCbHP group was higher than that of the AC-THP group, but the difference was not statistically significant (64.10% vs. 56.25%, P=0.441).No significant difference was found in the breast pathologic complete response (bpCR) and axillary pathologic complete response (apCR) rates between the TCbHP group and the AC-THP group (70.51% vs. 56.25%, P=0.150;78.21% vs. 84.38%, P=0.462).Exploratory analysis revealed that the tpCR rate of the TCbHP group was significantly higher than that of the AC-THP group in patients with HR-positive breast cancer (51.11% vs. 22.22%, P=0.036).As for the patients with HR-negative breast cancer, the tpCR rate of the AC-THP group tended to be higher than that of the TCbHP group (100% vs. 81.82%, P=0.088).The incidence of grade 3 or higher adverse reactions in the TCbHP group was slightly higher than that in the AC-THP group (12.82% vs. 9.38%, P=0.753).No deaths occurred in the whole group.Moreover, no significant difference was observed in the completion rate of the given approaches between the TCbHP group and the AC-THP group (92.31% vs. 90.63%, P=0.718). Conclusion In real-world clinical practice, the neoadjuvant therapy of TCbHP and AC-THP are effective, safe, and well tolerated among patients with HER2-positive breast cancer.The tpCR rate between the two approaches was not significantly different.The AC-THP regimen could also be considered as one of the optimal regimens for HER2-positive breast cancer in neoadjuvant therapy.

Analysis of a fetus with multiple malformations due to a hemizygous variant of FANCB gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with limb abnormality and cardiac malformation.@*METHODS@#Clinical data of a fetus diagnosed at the Shandong Provincial Maternal and Child Health Care Hospital on April 30th, 2021 was collected. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. X-inactivation analysis was carried out for the female members of its family.@*RESULTS@#The fetus was found to have meningoencephalocele, absence of bilateral radii, cleft lip, abnormal great arteries, and single umbilical artery at the gestational age of 11+ weeks. Sequencing revealed that the fetus has harbored a hemizygous c.1162del (p.Y388Tfs*7) variant of the FANCB gene, which was maternally inherited. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and ClinGen, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP4). X-inactivation analysis has revealed complete skewed X-inactivation in the pregnant woman and her mother.@*CONCLUSION@#The hemizygous c.1162del (p.Y388Tfs*7) variant of the FANCB gene probably underlay the multiple malformations in this fetus.

Controlling antifungal activity with light: Optical regulation of fungal ergosterol biosynthetic pathway with photo-responsive CYP51 inhibitors

Invasive fungal infections (IFIs) have been associated with high mortality, highlighting the urgent need for developing novel antifungal strategies. Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14α-demethylase (CYP51) inhibitors. The photocaged triazoles completely shielded the CYP51 inhibition. The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4% and 83.7%, respectively. Importantly, the shielded antifungal activity (MIC80 ≥ 64 μg/mL) could be efficiently recovered (MIC80 = 0.5-8 μg/mL) by light irradiation. The new chemical tools enable optical control of fungal growth arrest, morphological conversion and biofilm formation. The ability for high-precision antifungal treatment was validated by in vivo models. The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model. Overall, this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.

Overview of the main biological mechanisms linked to changes in periodontal ligament stem cells and the inflammatory microenvironment / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Periodontitis is a complex chronic inflammatory disease. The invasion of pathogens induces the inflammatory microenvironment in periodontitis. Cell behavior changes in response to changes in the microenvironment, which in turn alters the local inflammatory microenvironment of the periodontium through factors secreted by cells. It has been confirmed that periodontal ligament stem cells (PDLSCs) are vital in the development of periodontal disease. Moreover, PDLSCs are the most effective cell type to be used for periodontium regeneration. This review focuses on changes in PDLSCs, their basic biological behavior, osteogenic differentiation, and drug effects caused by the inflammatory microenvironment, to provide a better understanding of the influence of these factors on periodontal tissue homeostasis. In addition, we discuss the underlying mechanism in detail behind the reciprocal responses of PDLSCs that affect the microenvironment.

Clinical characteristics and influencing factors of onset age in inpatients with early- and late-onset obsessive-compulsive disorder inpatients / 四川精神卫生

BackgroundThe obsessive-compulsive disorder （OCD） features complexity in etiological factors and high heterogeneity in clinical manifestations. OCD patients with different ages of onset vary in clinical symptoms and etiology. However， current studies on inpatients with early- and late-onset OCD are limited. ObjectiveTo explore the differences in clinical characteristics between early- and late-onset OCD inpatients as well as the factors affecting the onset age of OCD， so as to provide references for early screening and treatment of OCD patients. MethodsThis study was based on collected medical records of 540 patients with OCD who received inpatient treatments at the Affiliated Brain Hospital of Nanjing Medical University between March 2012 and March 2023. Patients with onset age above 18 were placed into early-onset group （n=310） and the others into late-onset group （n=230）. Then differences in demographic data and clinical symptoms between two groups of patients were compared. Binary logistic regression was used to analyze the factors that affect the onset age of OCD. ResultsObserving the demographic data， there were significant differences between the two groups in the results in gender， marital status， family history of mental illness， ratio of comorbidities with other mental illnesses， occupational composition， education level and types of obsessive-compulsive symptoms （χ2=22.302、170.556， 9.224， 13.624， 242.277， 59.791， 7.231， P<0.05 or 0.01）. Also， the results in ages of onset and hospitalization between two groups were significantly different （Z=-19.915， 16.831， P<0.01）. In terms of clinical symptoms， the early onset group had a higher proportion of symptoms including obsessive thinking （χ2=11.998， P<0.05）， ordering （χ2=7.731， P<0.05） and rituals （χ2=7.714， P<0.05）， while the proportion of obsessive checking （χ2=8.204， P<0.05） and washing （χ2=7.506， P<0.05） symptoms were relatively low. In terms of risk factors， there were several independent risk factors that influence the onset age of OCD inpatients， including comorbid neurodevelopmental disorder， comorbid affective disorder， family history of schizophrenia and family history of affective disorder （OR=19.587， 1.830， 3.065， 4.431， P<0.05）. Among them， comorbid neurodevelopmental disorder was the core influencing factor， and female gender was a protective factor for early-onset patients （OR=0.417， P<0.01）. ConclusionThere are differences in demographic data and clinical symptom characteristics between early- and late-onset OCD inpatients， and comorbid neurodevelopmental disorder plays as a core risk factor affecting the onset age of OCD inpatients. ［Funded by Jiangsu Province Key Research and Development Plan for Social Development Special Project（number， BE2021616） ； Jiangsu Province Social Development General Project （number， BE2022678）； Key Project of Nanjing Medical Science and Technology Development Fund （number， ZKX20029）］

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

JNK inhibitor SP600125 inhibits interleukin-1β induced pyroptosis in βTC-6 cells / 中华内分泌代谢杂志

Objective:To investigate whether interleukin(IL)-1β is involved in pyroptosis which leads to mouse islet β cell line βTC-6 cell damage, and to explore the role of JNK inhibitor SP600125 in inhibiting IL-1β induced βTC-6 cell pyroptosis.Methods:βTC-6 cell line and mouse islets were incubated with IL-1β for 48 h or intervened with both JNK inhibitor SP600125 and IL-1R antagonist IL-1Ra, then GSDMD expression and β cell pyroptosis morphology were detected by immunofluorescence staining of GSDMD and DAPI. The expression levels of Gsdmd, IL-1β and IL-18 mRNAs were detected by real time fluorescence PCR, and apoptosis was examined by Annexin-V/7-AAD staining combined with flow cytometry.Results:βTC-6 cell pyroptotic body was significantly increased in the IL-1β treated group compared with the control group, and the expressions of pyroptosis related genes Gsdmd, IL-1β, and IL-18 mRNA were significantly higher( P<0.05), and apoptosis was increased, suggesting that IL-1β effectively induced the βTC-6 cell pyroptosis, IL-1Ra prevented IL-1β induced βTC-6 cell pyroptosis. In the presence of JNK inhibitor SP600125, IL-1β treatment failed to induce the expressions of Gsdmd and IL-18 mRNA, markers of pyroptosis, and reduced the rate of apoptosis, indicating that SP600125 suppressed IL-1β induced βTC-6 cell pyroptosis. Conclusion:Pyroptosis is one of the mechanisms of βTC-6 cell impairment caused by IL-1β, and SP600125, a JNK inhibitor, can block the IL-1β induced pyroptosis pathway and has a potential role in inhibiting βTC-6 cell pyroptosis.

Endoscopic treatment of gastric adenocarcinoma of the fundic gland: a report of three cases and a literature review / 中华老年医学杂志

Objective:To analyze and summarize the clinical characteristics, endoscopic manifestations, pathology and treatment of gastric adenocarcinoma of the fundic gland(GA-FD)to promote clinicians' understanding of this disease.Methods:The clinical data of 3 patients with GA-FD admitted to Beijing Hospital from May 2020 to January 2022 were retrospectively analyzed.Among them, 2 presented with abdominal distension or abdominal pain.The other case was diagnosed during follow-up endoscopy after gastrectomy for gastric cancer.A diagnosis of GA-FD was made based on the results of white light imaging, magnifying endoscopy, pathology and immunohistochemistry.In addition, we reviewed the literature about GA-FD between January 1990 and April 2021 from both national and international reports of 195 cases.We analyzed and summarized the endoscopic and pathological characteristics of the disease and insights on its diagnosis and treatment.Results:Of all 198 cases, patients had a male/female ratio of 1.6/1.0 and an average age of 65.3 years(range: 39-87 years).79.82%(91/114)of the patients were negative for Helicobacter pylori.Gastroscopy showed that the average diameter was 8.97 mm, and 89.9%(178/198)of the patients had lesions infiltrating into the submucosa.91.98%(149/162)of the patients had gastric chief cells as the predominant cell type, 98.86%(130/140)had no lymphovascular invasion, and 97.6%(162/166)had no recurrence or metastasis.Conclusions:GA-FD is a rare gastric cancer, with low-grade atypia and highly differentiated tissues.The mechanisms of GA-FD are not clear and the disease is more commonly seen in the elderly.There is no obvious correlation between Helicobacter pylori infections and GA-FD.Gastric chief cells make up the predominant cell type.The results of endoscopy, pathology and immunohistochemistry can help confirm the diagnosis.The prognosis of most cases is good.

Application of echo-planar imaging correction in diffusion weighted imaging and diffusion tensor imaging of cervical spinal cord / 中华放射学杂志

Objective:To explore the value of echo-planar imaging correction (EPIC) for improving image quality of diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) of cervical cord.Methods:A total of 33 subjects (20 males, 13 females) were scanned on a 3.0 T MR scanner from January to March 2022, and the sequences included T 1WI, DWI and DTI (with and without corrections). Two observers delineated the regions of interest (ROIs) on the fused images of DWI and DTI with T 1WI before and after correction, and measured the average diffusion coefficient (ADC), fractional anisotropy (FA), and offset distance of ROIs between images with and without corrections. The subjective scores of image quality were also evaluated. The ICC or Kappa was used to test the consistency of the quantitative measurement and subjective scores by the two observers. The average values by the two observers would be used for subsequent analysis. The independent pair t-test and Wilcoxon test were used for comparison of objective measurements and Mann-Whitney U test was used for subjective image assessments between images with and without corrections. Results:The measurement data and the subjective scores of the two observers were in good agreement (ICC 0.912-0.999, Kappa 0.778-0.816). The independent sample t-test showed the subjective scores were significantly different for the DWI and DTI images between before and after geometry and/or ADC corrections. The ADC values of C6, the offset distances measured by DWI before and after correction of C4, C5, and C6 and subjective scores were significantly different ( P<0.05); The FA values of C1 and C3, ADC values of C1 and C3, offset distance of C4, C5 and C6 measured by DTI before and after correction and subjective scores were statistically significant ( P<0.001). Conclusion:EPI geometry correction and ADC value correction can significantly reduce geometric distortion, increase image quality, and thus improve the diagnosis accuracy of essential diseases.

Rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by diagnostic bronchoscopy / 中华危重病急救医学

Objective:To explore the rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by bedside diagnostic bronchoscopy, so as to start effective anti-infection treatment before the results of macrogenome next generation sequencing (mNGS) test. Methods:The clinical data of three patients with severe Chlamydophila psittaci pneumonia who were successfully treated in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Aksu District, and the First Division Hospital of Xinjiang Production and Construction Corps from October 2020 to June 2021 were retrospectively analyzed, including the rapid assessment of early pathogens by bedside diagnostic bronchoscopy and the use of antibiotics to start anti-infection treatment. These patients were successfully treated. Results:The three patients were male, aged 63, 45 and 58 years old, respectively. Before the onset of the penumonia, they had a clear medical history of bird exposure. The clinical manifestations mainly included fever, dry cough, shortness of breath and dyspnea. One case had abdominal pain and lethargy. The results of laboratory examination indicated that the peripheral blood white blood cell count (WBC) of two patients were high [(10.2-11.9)×10 9/L], the percentage of neutrophils increased (85.2%-94.6%) and the percentage of lymphocytes decreased (3.2%-7.7%) in all 3 patients after admission to hospital and entering into intensive care unit (ICU). The procalcitonin (PCT) of 3 patients increased after admission, and still increased when entering ICU (0.3-4.8 ng/L), so did C-reactive protein (CRP, 58.0-162.0 mg/L) and erythrocyte sedimentation rate (ESR, 36.0-90.0 mm/1 h). After admission, serum alanine transaminase (ALT) increased in 2 cases (136.7 U/L, 220.5 U/L), so did aspartate transaminase (AST) in 2 cases (249.6 U/L, 164.2 U/L). ALT (162.2-267.9 U/L) and AST (189.8-223.2 U/L) increased in 3 patients when they entered ICU. The level of serum creatinine (SCr) of 3 patients were normal after admission and entering ICU. The chest computed tomography (CT) findings of 3 patients were acute interstitial pneumonia, bronchopneumonia and lung consolidation, of which 2 cases were accompanied by a small amount of pleural effusion, and 1 case was accompanied by more regular small air sacs. Multiple lung lobes were involved, but mainly one lung lobe. The oxygenation index (PaO 2/FiO 2) of the 3 patients admitting to ICU were 100.0, 57.5 and 105.4 mmHg (1 mmHg ≈ 0.133 kPa), respectively, which met with the diagnostic criteria of moderate and severe acute respiratory distress syndrome (ARDS). All three patients received endotracheal intubation and mechanical ventilation. Under the bedside bronchoscope, the bronchial mucosa of 3 patients were obviously congested and edematous, without purulent secretion, and there was 1 case with mucosal hemorrhage. Three patients underwent bedside diagnostic bronchoscopy, and the evaluation result of the pathogen was that it might be atypical pathogen infection, so they were given moxifloxacin, cisromet and doxycycline intravenously, respectively, and combined with carbapenem antibiotics intravenously. After 3 days, the detection results of mNGS in bronchoalveolar lavage fluid (BALF) showed that only Chlamydia psittaci was infected. At this time, the condition was significantly improved, and PaO 2/FiO 2 was significantly increased. Therefore, the antibiotic treatment scheme remained unchanged, and mNGS only served to verify the initial diagnosis. Two patients were extubated on the 7th and 12th day of admission to the ICU, respectively, while one patient was extubated on the 16th day of admission to the ICU due to nosocomial infection. All 3 patients were transferred to the respiratory ward after the condition was stable. Conclusion:The bedside diagnostic bronchoscopy based on clinical characteristics is conducive to not only the rapid assessment of the early pathogens of severe Chlamydia psittaci pneumonia, but also effective anti-infection treatment before the returning of mNGS test results, which can make up for the lag and uncertainty of the mNGS test results.

Meta-analysis of clinical prognosis of stage Ⅰ breast reconstruction after modified radical mastectomy / 中国医师进修杂志

Objective:To evaluate the clinical prognosis of stage Ⅰ breast reconstruction after modified radical mastectomy by using Meta-analysis.Methods:Wanfang Resource Database, Chinese Journal Full-Text Database, VIP Information Resource System, Chinese Scientific and Technological Journal Database, Cochrane Library, EMbase, PubMed were searched by computer. The retrieval time was from the establishment of each database to August 25, 2021. To collect clinical control test group (CCT) and randomized controlled trial(RCT) on breast reconstruction after radical mastectomy. The researchers independently searched the inclusion and exclusion criteria, screened and sorted them, evaluated them, extracted relevant data, and performed Meta-analysis with Rev man 5.3 software.Results:Twelve research were enrolled in this study.the Meta-analysis results showed that there were no significant differences in the local recurrence rate, distant metastasis rate, 3-year tumor free survival rate and complications between the patients performed stage Ⅰ breast reconstruction after modified radical mastectomy and the patients only performed modified radical mastectomy ( OR = 0.91, 95% CI 0.50 - 1.68, P = 0.77; OR = 0.66, 95% CI 0.42 - 1.06, P = 0.09; OR = 1.22, 95% CI 0.77 - 1.93, P = 0.40; OR = 0.91, 95% CI 0.58 - 1.41, P = 0.66). The quality of life score in the patients performed stage Ⅰ breast reconstruction after modified radical mastectomy was higher than that in the patients only performed modified radical mastectomy ( MD = 9.79, 95% CI 8.82 - 10.76, P<0.001). Conclusions:StageⅠbreast reconstruction after modified radical mastectomy can reduce the pressure of patients due to physical defects, help patients build up confidence and improve their quality of life.

Clinical efficacy evaluation of accelerated epithelium-off corneal collagen cross-linking on corneal ectasia after keratorefractive surgery / 中华实验眼科杂志

Objective:To investigate the efficacy and safety of accelerated epithelium-off corneal collagen cross-linking (CXL) in the treatment of corneal ectasia after keratorefractive surgery.Methods:An observational case series study was performed.Twelve patients (22 eyes) diagnosed with corneal ectasia after keratorefractive surgery in the First Affiliated Hospital of Army Medical University were enrolled from January 2016 to December 2018.All the patients received accelerated epithelium-off CXL and were followed up for 12 months.Before and 1 week, 1, 3, 6, and 12 months after the operation, the uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) converted to the logarithm of the minimum angle of resolution (LogMAR) unit were measured.The sphericity, cylindricity, and spherical equivalent were examined by Topcon auto refractor.The maximum keratometry (Kmax) of the front surface, mean keratometry (Km) of the front surface, Km of the back surface, symmetry index of front surface (SIf), symmetry index of back surface (SIb), thinnest corneal thickness (TCT), total aberrations, total high-order aberrations, coma aberration, trefoil aberration and spherical aberration were detected by the Sirius analyzer.The depth of corneal demarcation lines was determined by optical coherence tomography.The intraocular pressure was measured by the non-contact tonometry.The corneal endothelial cell density was assayed by the endothelial cell densitometry.The inflammatory reaction and haze were observed with a slit lamp at different time points after surgery.This study adhered to the Declaration of Helsinki.The study protocol was approved by the First Affiliated Hospital of Army Medical University (No.KY2020063). Written informed consent was obtained from each patient before entering the cohort.Results:Among the 22 eyes of 12 cases, 3 eyes of 2 cases (13.64%) underwent small incision lenticule extraction, and 19 eyes of 10 cases (86.36%) underwent excimer laser in situ keratomileusis.The UCVA (LogMAR), BCVA (LogMAR), cylindricity and spherical equivalent before the operation were 0.61±0.42, 0.24±0.23, (-2.83±2.39)D, (-3.60±2.66)D, which were significantly worse than 0.45±0.31, 0.12±0.15, (-2.11±1.67)D, (-3.12±2.31)D at 12 months after the operation ( t=4.054, 4.956, -3.728, -2.742; all at P<0.05). The front surface Kmax, front surface Km and SIf at 12 months after the operation were (48.37±5.80), (41.49±3.04), (5.36±4.07)D, which were significantly lower than (49.61±5.97), (41.66±2.97), (5.85±4.18)D before the operation ( t=5.949, 2.278, 2.719; all at P<0.05). There was no significant difference in sphericity, Km of the back surface, SIb, TCT, total aberrations, total high-order aberrations, coma aberration, trefoil aberration, spherical aberration, intraocular pressure and endothelial cell density between before and 12 months after the operation (all at P>0.05). Grade 0.5-2 haze occurred in 8 eyes of 4 patients one month postoperatively.After administration of prednisolone acetate eye drops, haze decreased or disappeared 3 months postoperatively, with UCVA and BCVA unchanged.A corneal demarcation line with a depth of (285.40±51.61)μm was found in 11 eyes of 6 cases at 1 month after operation. Conclusions:Accelerated epithelium-off CXL can significantly improve visual acuity, reduce corneal astigmatism and corneal curvature, as well as effectively prevent the progress of corneal ectasia.

Developmental and epileptic encephalopathy with dyskinesia caused by the FRRS1L gene mutation: a case report and literature review / 中华实用儿科临床杂志

The clinical characteristics and gene mutation profiles of a child who was treated in Xuzhou Children′s Hospital, Xuzhou Medical University in June 2022 due to developmental and epileptic encephalopathy (DEE) combined with dyskinesia caused by the FRRS1L gene mutation was analyzed retrospectively.A male case 1 year and 9 months old presented developmental delay since childhood, hypotonia at the age of 6 months, treatment-resistant seizures (focal clonic seizures) at the age of 1 year and 7 months that were unable to be controlled by antiepileptic drugs, and developmental regression and abnormal movements of the hands and feet during the attack.Whole exome sequencing showed 2 heterozygous variants (missense mutation and deletion mutation) in the FRRS1L gene of the child.The missense mutation c. 754C>T (p.R252C) located in the 4 th exon was inherited from his mother, and the deletion mutation c. 438_c.459del (p.I146fs*4) located in the 2 th exon was inherited from his father, thus constituting a compound heterozygous mutation.Through literature review, all 6 relevant literatures involving 31 children with DEE were published in foreign countries.They presented similar clinical manifestations to this case, but the genotypes were different, all of which were homozygous mutations.The FRRS1L gene mutation can lead to DEE, which is characterized by the autosomal recessive inheritance pattern, refractory epilepsy onset in infancy, developmental regression and prominent dyskinetic movements with hyperkinesia, and poor long-term prognosis.

The correlation between the expression levels of vitamin D receptor in bile duct epithelial cells and the prognosis of biliary atresia / 国际儿科学杂志

Objective:To investigate the expression of vitamin D receptor(VDR)in biliary epithelial cells of children with biliary atresia(BA)and explore the correlation between VDR epression levels and clinical pathological prognosis.Methods:A total of 48 BA patients who underwent Kasai surgery in the Pediatric Surgery Department of the Second Affiliated Hospital of Xi′an Jiaotong University from January 2017 to December 2020 with confirmed pathological results were selected as the study subjects.Immunohistochemistry was used to determine the expression of VDR in biliary epithelial cells, and Masson staining was used to determine the degree of liver tissue fibrosis.Based on the VDR expression levels, the 48 BA patients were divided into the significantly low VDR expression group(30 cases)and the normal/high expression group(18 cases).Laboratory testing results within 1 week before Kasai surgery and liver shear wave elastography(SWE)data were collected for all patients.Follow-up was conducted for a period of 0 to 60 months after Kasai surgery or liver transplantation, meanwhile, the occurrence of refractory cholangitis and auto-liver survival time were collected.Results:There was a negative correlation between the degree of liver fibrosis and SWE value in children with BA( r=-0.805, P<0.01).In comparison between the two groups, the significantly low VDR expression group had higher SWE values[(20.57±1.28)kPa vs.(18.02±1.41)kPa, P<0.05], higher liver injury biochemical indicators[ALT(215.8±24.7)U/L vs.(182.6±21.2)U/L, P=0.021; AST(165.4±22.3)U/L vs.(139.6±21.4)U/L, P=0.014], a higher frequency of post-Kasai surgery refractory cholangitis(60.00% vs.22.22%, P=0.037), and a shorter median autologous liver survival time(27.00 months vs.36.00 months, P=0.032)than those in the normal/high expression group. Conclusion:The significant decrease in VDR expression in biliary epithelial cells may serve as an indicator of poor prognosis in BA.