[TFE3-rearranged perivascular epithelioid cell tumors: a clinicopathological analysis of eight cases].

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of TFE3-rearranged perivascular epithelioid cell tumor (PEComa). Methods: Eight cases of PEComa with TFE3 rearrangement diagnosed in the First Affiliated Hospital of Air Force Medical University from January 2014 to July 2022 were collected. Three were consultation cases and 5 were collected from our hospital; 7 cases were resection specimens and 1 case was a needle biopsy specimen. Routine histolopathological analysis, immunohistochemical staining, fluorescence in situ hybridization (FISH) and the next-generation sequencing were performed. Clinical data were collected and the prognosis was assessed. Results: The 8 patients consisted of 5 females and 3 males with a median age of 45 years (ranged from 25 to 65 years). The tumor location included 1 uterus, 1 liver, 1 urachus, 2 kidneys, 1 abdominal cavity, 1 colon, and 1 retroperitoneum (3 subsequent recurrences in the abdominal cavity, pelvis and ovary, and abdominal cavity, respectively). Morphologically, the tumor cells were uniform and epithelioid with translucent or eosinophilic cytoplasm. They were arranged in nests or sheets, most of which were separated by thin-walled blood vessels. There were no papillary structures, and no overt smooth muscle or fat components. Atypical features were seen in 3 cases, with bizarre nuclei and tumor giant cells. Large areas of necrosis were visible, and mitosis was common (up to 28/50 HPF). Melanin deposition was present in 3 cases. Immunohistochemical staining showed diffuse and strong positivity for TFE3 in 8/8 cases and for HMB45 in 6/8 cases; focal positivity for Cathepsin K and Melan-A in 6/8 cases and for SMA in 2/8 of cases. All cases were negative for CKpan, PAX8 and Desmin. TFE3 gene break-apart was detected by FISH in all 8 cases, 4 of which underwent next-generation sequencing, and it revealed that 2 cases presented with SFPQ::TFE3 fusion, 1 case with ASPSCR1::TFE3 fusion, and 1 case with no chimeric fusion. Seven cases were followed up for 4-94 months. All cases were alive; 4 cases were disease-free, 2 cases showed recurrence, and 1 case had metastasis at initial diagnosis. Conclusions: TFE3-rearranged PEComa has unique histomorphological, immunohistochemical and molecular characteristics. The biological behavior is aggressive, which could lead to recurrence and metastasis, and warrants close clinical follow-up.

Epoxyeicosatrienoic Acids Attenuate LPS-Induced NIH/3T3 Cell Fibrosis through the A2AR and PI3K/Akt Signaling Pathways.

Inflammation plays a crucial role in progression of fibrosis. Epoxyeicosatrienoic acids (EET) have multiple protective effects in different diseases, but their ability to inhibit the development of LPS-induced fibrosis remains unknown. The potential therapeutic effects of 11,12-EET were studied in in vitro model of LPS-induced fibrosis. Mouse embryonic fibroblast cells NIH/3T3 were pre-incubated with 1 µM 11,12-EET and/or a structural analogue and selective EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid before exposing to LPS. The effect of EET was evaluated by the protein and mRNA expression of NF-κB, collagens I and III, and α-smooth muscle actin by Western blotting and quantitative reverse transcription PCR, respectively. LPS provoked inflammation and fibrosis-like changes accompanied by elevated expression of NF-κB and collagens in NIH/3T3 cells. We also studied the effects of 11,12-EET on the A2AR and PI3K/Akt signaling pathways in intact and LPS-treated NIH/3T3 cells. 11,12-EET prevented inflammation and fibrosis-like changes through up-regulation of A2AR and PI3K/Akt signaling pathways. Our findings demonstrate the potential antifibrotic effects of 11,12-EET, which can be natural antagonists of tissue fibrosis.

Effect of Month of Birth on Mean Birth Length in Austrian Newborns Born Between 1984 and 2021.

OBJECTIVE: The length of newborns shows seasonal fluctuations, but the patterns of these fluctuations vary greatly. This study analyses the fluctuation in birth length by birth month and temporal changes in Austrian newborns from the 1984 to 2021 birth cohorts. METHODS: A total of 2 317 927 singleton-term births between 1984 and 2021 in Austria were included in this retrospective population-based cohort study. A strict inclusion criterion was the Austrian citizenship of the mother. The effect of month of birth (MOB) on birth length was estimated using a multivariable linear model adjusting for maternal educational level, newborn sex, gestational age, year of birth (YOB) of the newborn, and parity of the mother. RESULTS: Newborn length varied by MOB, but there was also a temporal trend. In the birth cohorts up to 2004, the longest newborns were born in February, while from 2008 onward, the longest birth lengths were observed in the summer months. CONCLUSION: In this Austrian population-based sample, birth length shows nonrandom fluctuations by birth month. These patterns, however, varied considerably over time.

Association between non-alcoholic fatty liver disease and metabolic abnormalities in children with different weight statuses.

OBJECTIVES: Both obesity and non-alcoholic fatty liver disease (NAFLD) increase the risk of metabolic abnormalities. However, the metabolic status of children suffering from NAFLD and exhibiting various subtypes of obesity is currently unclear. We aimed to explore the association between NAFLD and metabolic abnormalities in children with different weight statuses. METHODS: We included 6086 participants aged 6-18 years from the China Child and Adolescent NAFLD Study (CCANS), all of whom had undergone ultrasonography or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to identify NAFLD and metabolic abnormalities, including hyperglycemia, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol, high total cholesterol, and hyperuricemia. RESULTS: Among the participants, there were 2408 children with obesity and NAFLD, 174 with NAFLD, 2396 with obesity, and 1108 without obesity and NAFLD. The odds ratios (ORs) of suffering from individual metabolic abnormalities were significantly greater in children with obesity and NAFLD than in children without obesity and NAFLD, with ORs ranging from 6.23 (95% CI: 4.56, 8.53) to 1.77 (95% CI: 1.06, 2.94). The ORs of metabolic abnormalities, except for low HDL-C, were greater in children with NAFLD alone than in children without obesity or NAFLD, with ORs ranging from 4.36 (95% CI: 2.77, 6.84) to 2.08 (95% CI: 1.14, 3.78). Notably, obesity and NAFLD had a multiplicative effect on overall metabolic abnormalities, high TG levels, and low HDL-C levels. CONCLUSIONS: Children with obesity and NAFLD could be at a significantly increased risk of metabolic abnormalities. Even for children without obesity, NAFLD appears to be associated with an increased risk of experiencing a worsened metabolic status.

[Clinical analysis on the impact of pretransplant iron overload on allogeneic hematopoietic stem cell transplantation for patients with acquired severe aplastic anemia in pediatric].

This study aimed to investigate the effect of iron overload on the transplant outcomes of pediatric patients with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A retrospective analysis was conducted on the clinical data of 74 children with SAA who received allo-HSCT at the Hematology Department of Wuhan Children's Hospital between January 2018 and August 2022. Children with iron overload (serum ferritin >1 000 µg/L) before transplantation had a longer disease course, received more red blood cell transfusions, and had a higher number of CD34(+) cells infused. Moreover, iron overload significantly delayed the reconstitution of regulatory T cells after transplantation, increasing the incidence of hemorrhagic cystitis and grade Ⅲ-Ⅳ acute graft-versus-host disease after transplantation. However, iron overload did not significantly affect the overall survival and failure-free survival rates of the children.

Deep-learning features based on F18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to predict preoperative colorectal cancer lymph node metastasis.

AIM: The objective of this study was to create and authenticate a prognostic model for lymph node metastasis (LNM) in colorectal cancer (CRC) that integrates clinical, radiomics, and deep transfer learning features. MATERIALS AND METHODS: In this study, we analyzed data from 119 CRC patients who underwent F18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning. The patient cohort was divided into training and validation subsets in an 8:2 ratio, with an additional 33 external data points for testing. Initially, we conducted univariate analysis to screen clinical parameters. Radiomics features were extracted from manually drawn images using pyradiomics, and deep-learning features, radiomics features, and clinical features were selected using Least Absolute Shrinkage and Selection Operator (LASSO) regression and Spearman correlation coefficient. We then constructed a model by training a support vector machine (SVM), and evaluated the performance of the prediction model by comparing the area under the curve (AUC), sensitivity, and specificity. Finally, we developed nomograms combining clinical and radiological features for interpretation and analysis. RESULTS: The deep learning radiomics (DLR) nomogram model, which was developed by integrating deep learning, radiomics, and clinical features, exhibited excellent performance. The area under the curve was (AUC = 0.934, 95% confidence interval [CI]: 0.884-0.983) in the training cohort, (AUC = 0.902, 95% CI: 0.769-1.000) in the validation cohort, and (AUC = 0.836, 95% CI: 0.673-0.998) in the test cohort. CONCLUSION: We developed a preoperative predictive machine-learning model using deep transfer learning, radiomics, and clinical features to differentiate LNM status in CRC, aiding in treatment decision-making for patients.

[Pedigree Analysis and Molecular Mechanism Study of Hereditary Glanzmann Thrombasthenia Caused by Compound Heterozygous Mutation of the ITGA2B Gene].

Objective: The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored. Methods: The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (ß3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and ß3 in platelets were analyzed by Western blot. Results: Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and ß3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5'SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the ß-propeller domain of the p.S160-S192 deletion lost two ß-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a ß chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of ß3 was 11.36% of the normal level. Conclusion: The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.

[Clinical characteristics and prognostic analysis of 34 patients with primary thyroid lymphoma].

Objective: To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) . Methods: A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors. Results: All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis (P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion: PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

[Interpretation on the report of global cancer statistics 2022].

In April 2024, the World Health Organization/International Agency for Research on Cancer (IARC) published the global cancer statistics 2022 in the CA: Cancer Journal for Clinicians. This report focuses on the incidence and mortality of 36 cancers in 185 countries or territories worldwide, analyzing the differences of gender, geographic region, and the Human Development Index (HDI) level. It is estimated that in the year 2022, there were 19.96 million new cancer cases and 9.74 million cancer deaths worldwide. Lung cancer (2 480 301, 12.4%) was the most frequently diagnosed cancer in 2022, followed by female breast cancer (2 295 686, 11.5%), colorectal cancer (1 926 118, 9.6%), prostate cancer (1 466 680, 7.3%), and gastric cancer (968 350, 4.9%). Lung cancer (1 817 172, 18.7%) was also the leading cause of cancer death, followed by colorectal cancer (903 859, 9.3%), liver cancer (757 948, 7.8%), female breast cancer (665 684, 6.9%), and gastric cancer (659 853, 6.8%). With demographics-based predictions indicating that the number of new cases of cancer will reach over 35 million by 2050. The Beijing Office for Cancer Prevention and Control team has collated this report and briefly interpreted it in combination with the current situation of cancer incidence and mortality in China.

[Efficacy analysis of letrozole combined with gonadotropin-releasing hormone antagonists in patients with high risk of ovarian hyperstimulation syndrome undergoing total embryo freezing].

Objective: To investigate the clinical efficacy of letrozole combined with gonadotropin-releasing hormone antagonists (GnRH-ant) in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who underwent total embryo freezing after oocyte retrieval. Methods: A retrospective analysis was conducted on 348 female patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive and Genetic Hospital of the First Affiliated Hospital of Zhengzhou University between January and July 2023. Due to their high risk of OHSS, these patients canceled fresh embryo transfer and opted for total embryo freezing. Based on patients' preferences, those who received GnRH-ant and letrozole after oocyte retrieval were categorized as the intervention group (164 cases), while those who did not receive these medications were categorized as the control group (184 cases). The first luteal phase after oocyte retrieval, OHSS grading, ovarian volume, and estradiol (E2) levels were evaluated in both groups. A multivariate logistic regression model was used to analyze factors related to moderate-to-severe OHSS among patients at high risk of OHSS who underwent total embryo freezing after oocyte retrieval. Results: The age of the intervention and control groups was (29.3±3.8) and (29.4±4.1) years, respectively (P=0.821). The duration of the first luteal phase post-oocyte retrieval was shorter in the intervention group [(7.16±1.39) days] compared to that in the control group [(13.88±2.11) days] (P<0.001). The incidences of mild, moderate, and severe OHSS in the intervention group were 75.0% (123 cases), 23.8% (39 cases), and 1.2% (2 cases), respectively, whereas in the control group they were 12.5% (23 cases), 60.9% (112 cases), and 26.6% (49 cases) (P<0.001). E2 levels on the 2nd and 6th days after oocyte retrieval [M(Q1,Q3)] in the intervention group were 1 520.0 (1 213.8, 1 884.8) and 108.5 (45.6, 218.0) ng/L, respectively, which were statistically significantly lower than those in the control group [1 666.0 (508.8, 1 702.0) ng/L] and [1 761.0 (826.0, 2 546.5) ng/L] (P<0.001). The abdominal cavity effusion in the intervention group [M(Q1,Q3)] were 19.5 (0, 30) and 0 mm, statistically significantly less than those in the control group [46.0 (0, 61.0) mm] and [54.5 (0, 69.5) mm] (P<0.001). On the 6th day after oocyte retrieval, the bilateral ovarian volumes in the intervention group were smaller than those in the control group (P<0.001). Multivariate logistic regression analysis indicated that no combined treatment with letrozole and GnRH-ant was a risk factor of moderate to severe OHSS. The risk of developing moderate to severe OHSS in the control group was 35.312 times higher than that in the intervention group (OR=35.312, 95%CI: 17.488-71.300). Conclusions: The administration of letrozole combined with GnRH-ant post-oocyte retrieval in patients at high risk of OHSS can prevent the occurrence of moderate-to-severe OHSS, shorten the first luteal phase, accelerate the reduction of serum E2 levels, and promote the recovery of ovarian volume and absorption of abdominal fluid.

[High expression of the stemness-associated molecule Nanog in esophageal squamous cell carcinoma tissues promotes tumor invasion and metastasis by activating the TGF-ß signaling pathway].

OBJECTIVE: To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma (ESCC). METHODS: We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients. GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog, and TIMER online tool was used to analyze the correlations among TßR1, MMP-2, and MMP-9 in esophageal cancer. RESULTS: Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated. Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age, gender, or tumor differentiation. The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time. Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-ß signaling pathway, and the expressions of MMP-2/MMP-9 and TßR1 were positively correlated. In cultured ESCC cells, Nanog knockdown significantly decreased the expression of TßR1, p-Smad2/3, MMP-2, and MMP-9 and strongly inhibited cell migration. CONCLUSION: The high expressions of Nanog, MMP-2, and MMP-9, which are positively correlated, are closely related with invasion depth, lymph node metastasis, and prognosis of ESCC. Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-ß signaling pathway, and its high expression promotes migration of ESCC cells.

[Experimental study on the artificial infection of common freshwater snails with Angiostrongylus cantonensis in Dali Bai Autonomous Prefecture, Yunnan Province].

OBJECTIVE: To evaluate the potential risk of transmission of angiostrongyliasis by common freshwater snails in Dali Bai Autonomous Prefecture, Yunnan Province, so as to provide insights into local surveillance of angiostrongyliasis. METHODS: Common freshwater snails were collected from Dali Bai Autonomous Prefecture, Yunnan Province from March to April, 2020, and identified and bred in laboratory. SD rats were infected with third-stage larvae of Angiostrongylus cantonensis that were isolated from commercially available Pomacea canaliculata snails in Dali Bai Autonomous Prefecture, and freshwater snails were infected with the first-stage larvae of A. cantonensis that were isolated from the feces of SD rats 39 days post-infection at room temperature. The developmental process and morphological characteristics of worms in hosts were observed, and the percentages of A. cantonensis infections in different species of freshwater snails were calculated. Then, SD rats were infected with the third-stage larvae of A. cantonensis that were isolated from A. cantonensis-infected freshwater snails, and the larval development and reproduction was observed. RESULTS: More than 3 000 freshwater snail samples were collected from farmlands, ditches and wetlands around Erhai Lake in Dali Bai Autonomous Prefecture, and Cipangopaludina chinensis, P. canaliculata, Parafossarulus striatulus, Oncomelania hupensis robertsoni, Galba pervia, Physa acuta, Radix swinhoei, Assiminea spp., Tricula spp. and Bellamya spp. were morphologically identified. A total of 105 commercially available P. canaliculata snails were tested for A. cantonensis infections, and 2 P. canaliculata snails were found to be infected with A. cantonensis, in which the third-stage larvae of A. cantonensis were isolated. Ten species of freshwater snails were artificially infected with the third-stage larvae of A. cantonensis, and all 10 species of freshwater snails were found to be infected with A. cantonensis, with the highest positive rate of A. cantonensis infections in Bellamya spp. (62.3%, 137/204), and the lowest in C. chinensis (35.5%, 11/31). After SD rats were infected with the third-stage larvae of A. cantonensis isolated from different species of freshwater snails, mature adult worms of A. cantonensis were yielded. CONCLUSIONS: Multiple species of freshwater snails may serve as intermediate hosts of A. cantonensis under laboratory conditions in Dali Bai Autonomous Prefecture of Yunnan Province. Further investigations on natural infection of A. cantonensis in wild snails in Dali Bai Autonomous Prefecture seem justified.

[Efficacy and safety study of standardized mite allergen specific immunotherapy with no reduction during maintenance in children with respiratory allergic disease].

Objective: To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance. Method: Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups. Results: A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant (χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups (χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status (t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment (t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years (t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points (t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment (t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing (t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years (t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE (t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 (t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion: Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.

Adherence to guidelines and central-line-associated bloodstream infection occurrence during insertion and maintenance of intravascular catheters: evidence from 20 tertiary hospitals.

OBJECTIVE: To investigate adherence to intravascular catheter (IVC) insertion and maintenance guidelines in Chinese tertiary hospitals. METHODS: A cross-sectional questionnaire survey of adult inpatients with IVC placements was conducted from July to September 2022 in 20 tertiary hospitals in China. One clinical staff member from each department in each hospital was assigned to participate in the survey. Questionnaires were uniformly collected and reviewed after three months. RESULTS: This study included 1815 cases (62.69%) of central venous catheter, 471 cases (16.27%) of peripherally inserted central catheter, 461 cases (15.92%) of PORT, and 147 cases (5.08%) of haemodialysis catheter insertions. Statistically significant differences in compliance were observed across the four IVC types, specifically in relation to the insertion checklist, standard operating procedure, and insertion environment (P<0.05). Practice adherence during IVC maintenance differed significantly across the four IVC types in aspects such as availability of IVC maintenance verification forms, daily scrubbing of the catheterized patients, and catheter connection methods (P<0.05). A total of 386 (13.34%) patients developed fever, 1086 (37.53%) were treated with therapeutic antibiotics, 16 (0.55%) developed central-line-associated bloodstream infections, two (0.07%) developed local skin infections, and six (0.21%) developed deep vein thrombosis. CONCLUSIONS: Adherence to guidelines regarding insertion and maintenance differed across the four IVC types; there is a gap between the recommended measures and the actual operation of the guidelines. Therefore, it is necessary to further enhance training and develop checklists to prevent central-line-associated bloodstream infections.

[Distribution and influencing factors of lipoprotein (a) levels in non-arteriosclerotic cardiovascular disease population in China].

Objective: To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors. Methods: This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels. Results: Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M (Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) (OR=1.23, 95%CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced (OR=0.68, 95%CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95%CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95%CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95%CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95%CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions: Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

[Copy number variations of CCND1 gene and chromosome 11 centromere in acral melanoma].

Objective: To study the correlation between the copy number variations of CCND1 gene and chromosome 11 and their associations with clinicopathologic features in acral melanoma. Methods: Thirty-three acral melanoma cases diagnosed at the Department of Pathology of Peking University Third Hospital, Beijing, China from January 2018 to August 2021 were collected. Fluorescence in situ hybridization (FISH) was used to detect the copy number of CCND1 gene and centromere of chromosome 11. The relationship between the copy numbers of CCND1 and chromosome 11 centromere, and the correlation between CCND1 copy number and clinicopathologic characteristics were analyzed. Results: There were 15 male and 18 female patients, with an age ranging from 22-86 years. 63.6% (21/33) of the patients had an increased CCND1 gene copy number. 21.2% (7/33) of patients with increased CCND1 copy number had an accompanying chromosome 11 centromere copy number increase. 27.3% (9/33) of the cases had a low copy number of CCND1 gene, and 4 of them (4/33, 12.1%) were accompanied by chromosome 11 centromere copy number increase. 36.4% (12/33) of the cases had a high copy number of CCND1 gene, and 3 (3/33, 9.1%) of them were accompanied by chromosome 11 centromere copy number increase. No cases with CCND1 low copy number increase showed CCND1/CEP11 ratio greater than 2.00. The 11 cases with CCND1 high copy number increase showed CCND1/CEP11 ratio greater than or equal to 2.00. However, there was no significant correlation between CCND1 copy number increase and any of the examined clinicopathologic features such as age, sex, histological type, Breslow thickness, ulcer and Clark level. Conclusions: CCND1 copy number increase is a significant molecular alteration in acral melanoma. In some cases, CCND1 copy number increase may be accompanied by the copy number increase of chromosome 11. For these cases the copy number increase in CCND1 gene may be a result of the copy number change of chromosome 11.

Establishment of a rabbit model of different degrees of testicular torsion.

INTRODUCTION AND OBJECTIVES: Different degrees of testicular torsion result in varying degrees of testicular damage, which influences treatment options and outcomes. Therefore, establishing a testicular torsion model with different degrees is necessary for clinical diagnosis. MATERIALS AND METHODS: Rabbits were randomly divided into four groups and their spermatic cords were twisted at 0 °, 180 °, 360 °, and 720 °, respectively. Color Doppler flow imaging (CDFI) were performed to evaluate the blood supply in testicles. The twisted testicles were surgically removed at six hours post-operation and were evaluated by morphological observation and Hematoxylin and Eosin staining. RESULTS: CDFI signals were gradually decreased as the degree of testicular torsion increased, and scores of CDFI in the 360 ° and 720 ° groups were significantly decreased at postoperative six hours compared to pre-surgery. Compared to the sham, the testicle in the 180 ° group exhibited slight congestion, whereas the testicles in the 360 ° and 720 ° groups were dark red in color and had severe congestion and unrecognizable vessels. Hematoxylin and Eosin staining showed mild spermatogenic cell reduction and testicular interstitial hemorrhage in the 180 ° group. In the 360 ° and 720 ° groups, disordered seminiferous tubules, shed spermatogenic cells in tubules, inflammatory cell infiltration, and severe hemorrhage were found. In comparison with the sham, interstitial hemorrhage scores in the 360 ° and 720 ° groups were significantly higher, and scores of germinal epithelial cell thickness in the three testicular torsion groups were significantly decreased. CONCLUSIONS: Collectively, we successfully constructed a testicular torsion model with different degrees in rabbits.

[Bmal1 mediates the neuroprotective effect of sodium butyrate in a mouse model of Parkinson's disease].

OBJECTIVE: To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate (NaB) in a mouse model of Parkinson's disease (PD) via the gut-brain axis. METHODS: Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group, PD model group, and NaB treatment group. In the latter two groups, PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) once daily for 5 consecutive days, and normal saline was injected in the control group. After modeling, the mice received daily gavage of NaB (300 mg/kg) or an equal volume of saline for 14 days. Behavioral tests were carried out to assess the changes in motor function of the mice, and Western blotting was performed to detect the expressions of tyrosine hydroxylase (TH) and α-synuclein (α-syn) in the striatum and nuclear factor-κB (NF-κB), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and the tight junction proteins ZO-1, Occludin, and Claudinin the colon. HE staining was used to observe inflammatory cell infiltration in the colon of the mice. RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues, and their expressions were verified using qRT-PCR and Western blotting. RESULTS: The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH, Occludin, and Claudin and downregulated expressions of α-syn, NF-κB, TNF-α, and IL-6 (all P < 0.05). HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice. RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice (P < 0.05). CONCLUSION: NaB can improve motor dysfunction, reduce dopaminergic neuron loss in the striatum, and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.

Meta-analysis Driven Strain Design for Mitigating Oxidative Stresses Important in Biomanufacturing.

As the availability of data sets increases, meta-analysis leveraging aggregated and interoperable data types is proving valuable. This study leveraged a meta-analysis workflow to identify mutations that could improve robustness to reactive oxygen species (ROS) stresses using an industrially important melatonin production strain as an example. ROS stresses often occur during cultivation and negatively affect strain performance. Cellular response to ROS is also linked to the SOS response and resistance to pH fluctuations, which is important to strain robustness in large-scale biomanufacturing. This work integrated more than 7000 E. coli adaptive laboratory evolution (ALE) mutations across 59 experiments to statistically associate mutated genes to 2 ROS tolerance ALE conditions from 72 unique conditions. Mutant oxyR, fur, iscR, and ygfZ were significantly associated and hypothesized to contribute fitness in ROS stress. Across these genes, 259 total mutations were inspected in conjunction with transcriptomics from 46 iModulon experiments. Ten mutations were chosen for reintroduction based on mutation clustering and coinciding transcriptional changes as evidence of fitness impact. Strains with mutations reintroduced into oxyR, fur, iscR, and ygfZ exhibited increased tolerance to H2O2 and acid stress and reduced SOS response, all of which are related to ROS. Additionally, new evidence was generated toward understanding the function of ygfZ, an uncharacterized gene. This meta-analysis approach utilized aggregated and interoperable multiomics data sets to identify mutations conferring industrially relevant phenotypes with the least drawbacks, describing an approach for data-driven strain engineering to optimize microbial cell factories.