[Primary mucinous gland lesions of fallopian tube: a clinicopathological analysis of fourteen cases].

Objective: To investigate the clinical and pathological characteristics of primary mucinous gland lesions of the fallopian tubes. Methods: The clinical data, pathomorphological characteristics and immunophenotype of 14 cases of primary mucinous gland lesions of the fallopian tube diagnosed at Obstetrics and Gynecology Hospital of Fudan University from 2015 to 2023 were analyzed retrospectively. In addition, a comprehensive review of relevant literature was conducted. Results: The age of 14 patients ranged from 53 to 83 years, with an average of 65 years. Among them, 13 cases exhibited unilateral involvement while one case showed bilateral presentation. Nine cases were mucinous metaplasia of the fallopian tube, four cases were invasive mucinous adenocarcinoma and one case was mucinous carcinoma in situ. Morphologically, mucinous metaplasia of the fallopian tube was focal, with or without inflammation. The cells of mucinous adenocarcinoma or mucinous carcinoma in situ exhibited characteristics indicative of gastrointestinal differentiation. Immunohistochemical analysis revealed diffuse positive expression of CK7, and negative expression of SATB2. CDX2 demonstrated positive staining in two cases. One case exhibited diffuse and strongly positive mutant expression of p53, whereas the remaining cases displayed wild-type expression. MUC6 showed diffuse or focally positive staining in mucinous gland lesions characterized by gastric differentiation. Some cases of mucinous adenocarcinoma of fallopian tube were subject to AB-PAS staining, resulting in red to purple cytoplasmic staining. Conclusions: Primary mucinous lesions of the fallopian tube are exceedingly uncommon. All cases of mucinous adenocarcinoma of fallopian tubes in this study exhibit the morphology and immunohistochemical characteristics of gastrointestinal differentiation. Mucinous metaplasia of the fallopian tube is a benign lesion of incidental finding, which is closely related to inflammation or gastric differentiation. Mucinous lesions of cervix, ovary and digestive tract are excluded in all patients, confirming the independent existence of mucinous lesions within fallopian tubes.

[Analysis of language and influencing factors of children with speech disorder in Beijing].

Objective: To investigate the features and influencing factors of language in children with various types of speech disorders. Methods: A case-control study was carried out, 262 children with speech disorder had been diagnosed at the language-speech clinic of the Center of Children's Healthcare, Children's Hospital, Capital Institute of Pediatrics from January 2021 to November 2023, the children with speech sound disorder as the speech sound disorder group, the children with developmental stuttering as the stuttering group. There were 100 typically-developed children who underwent physical checkups at the Center of Healthcare during the same period as the healthy group. All children experienced a standardized evaluation of language with diagnostic receptive and expressive assessment of mandarin-comprehensive(DREAM-C) and questionnaire, One-way ANOVA and LSD test were conducted to compare the differences in overall language, receptive language, expressive language, semantics, and syntax scores among 3 groups of children. According to the results of DREAM-C, the children with speech disorder were divided into language normal group and language delay group. Chi-square test and multivariate Logistic regression were implemented to analyze the association between the linguistic development of children with speech disorder and potential influential factors. Results: There were 145 children in the speech sound disorder group, including 110 males and 35 females respectively, with an age of (5.9±1.0) years; 117 children in the stuttering group, including 91 males and 26 females, with an age of (5.8±1.0) years; 100 children in the healthy group, including 75 males and 25 females, with an age of (5.7±1.2) years. The variations in overall language, expressive language, and syntax scores among 3 groups of children were statistically significant (92±18 vs.96±11 vs. 98±11, 81±18 vs. 84±14 vs. 88±13, 87±16 vs. 89±11 vs. 91±10, F=5.46, 4.69, 3.68, all P<0.05). Pairwise comparison revealed that the speech sound disorder group had lower scores in overall language, expressive language, and syntactic compared to the healthy group, and the differences were statistically significant (all P<0.01) and the overall language score was lower than that of children with stuttering (P<0.05). In terms of overall language and expressive language, there was a statistically significant difference in the incidence of language delay among the three groups of children (15.9% (23/145) vs. 20.5% (24/117) vs. 7.0% (7/100), 46.2% (67/145) vs. 39.3% (46/117) vs. 26.0% (26/100); χ2=7.93, 10.28; both P<0.05). In terms of overall language, the stuttering group took up the highest proportion. In terms of expressive language, the speech sound disorder group accounted for the highest amount. The incidence of language delay in children with speech disorder was 44.3% (116/262). Non-parent-child reading, daily screen time ≥1 hour and screen exposure before 1.5 years of age are risk factors for the development of language in children with speech disorder (OR=1.87, 2.18, 2.01; 95%CI 1.07-3.27, 1.23-3.86, 1.17-3.45; all P<0.01). Negative family history are protective factors for the progress of language ability (OR=0.37, 95%CI 0.17-0.81, P<0.05). Conclusions: Children with speech disorder tend to have easy access to language delay, especially in expressive language and syntax. The occurrence of language delay in children with speech disorder is tightly connected with factors such as the family medical history, parent-child reading, screen time, etc. Attention should be paid to the development of language in children who suffer from speech disorder.

[The diagnostic value of lung ultrasound in children with community-acquired pneumonia].

Objective: To investigate the diagnostic value of lung ultrasound in hospitalized children with community-acquired pneumonia (CAP). Methods: In the cross-sectional study, a total of 422 children with CAP who were hospitalized in the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, from February 2021 to August 2022 and completed lung ultrasound examination within 48 hours after admission were enrolled. The clinical characteristics, lung ultrasound and chest CT were collected. The patients were divided into two groups according to the signs of pneumonia indicated by chest CT, and the signs of lung ultrasound with diagnostic value were screened according to the signs of pneumonia indicated by chest CT by least absolute shrinkage and selection operator (Lasso) regression. According to severity of the disease, the children were divided into the severe group and the mild group, and the differences of lung ultrasound signs between the two groups were compared. Kruskal-Wallis test, Fisher's exact test was selected for comparison between groups. Random forest classifier wes used to evaluate the value of lung ultrasound in the diagnosis of CAP and prediction of severe pneumonia in children. The receiver operating characteristic curve was used to evaluate the prediction effect. Use DeLong test to compare the area under the curve. Results: Among the 422 cases of CAP, there were 258 males and 164 females, and the age of onset was 2.8 (1.3, 4.3) years. The confluent B-line, consolidation and pleural effusion detected by lung ultrasound were 309 cases (73.2%), 232 cases (55.0%) and 16 cases (3.8%), respectively, and the size of consolidation was 3.0 (0, 11.0) mm. One hundred and ten children (26.1%) with CAP completed chest CT. There were 90 cases with signs of pneumonia in chest CT and 20 cases without signs of pneumonia. Lasso was used for feature selection.Lung consolidation (OR=2.46), bilateral lung consolidation (OR=1.16) and confluent B-line (OR=1.34) were the main index. With random forest classifier, the accuracy of models using full variables and Lasso-selected variables were 0.79 (95%CI 0.70-0.86) and 0.79 (95%CI 0.70-0.86), the sensitivity were 0.81 and 0.81, and the specificity were 0.75 and 0.70, and the area under curve were 0.87 (95%CI 0.81-0.94, P<0.001) and 0.84 (95%CI 0.76-0.91, P<0.001), respectively. There were 97 cases in severe group and 325 cases in mild group. Compared with the mild group, the detection rate of consolidation, multiple consolidation, the size of consolidation and the size of consolidation was adjusted by body surface area (consolidation size/body surface area) in severe group were higher (66 cases (68.0%) vs. 166 cases (51.1%), 42 cases (43.3%) vs. 93 cases (28.6%), 8.0 (0, 17.0) vs. 1.0 (0, 9.0) mm, 12.5 (0, 24.6) vs. 2.1 (0, 17.6), χ2=8.59, 9.98, Z=14.40, 12.79, all P<0.05). Using lung ultrasound lung consolidation size and consolidation size/body surface area to predict the severe CAP, the optimal cut-off value were 6.7 mm and 10.2, the accuracy was 0.80 (95%CI 0.75-0.83) and 0.89 (95%CI 0.86-0.92), the sensitivity was 0.99 and 0.99, the specificity was 0.14 and 0.56, respectively, and the area under the curve was 0.66 (95%CI 0.60-0.72, P<0.001) and 0.76 (95%CI 0.70-0.83, P<0.001), respectively. The area under the curve of consolidation size/body surface area was higher than that of consolidation size (Z=5.50, P<0.001). Conclusions: Consolidation and confluent B-line, are important index for lung ultrasound diagnosis of CAP in children. The actual consolidation size adjusted by body surface area is superior to the size of consolidation in predicting severe CAP.

[Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China].

Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

[The imaging presentations of the fallopian canal cerebrospinal fluid leaking].

Objective: To summarize the imaging presentations of the fallopian canal cerebrospinal fluid leaking (FCCFL). Methods: The high resolution CT (HRCT)and MRI materials of 4 patients (4 ears) with FCCFL confirmed by surgery between August 2016 to November 2023 were retrospectively analyzed. Among these, there were 2 males and 2 females, their ages ranged from 6 to 69 years. Results: All of the FCCFL were unilateral, including 2 on the left and 2 on the right.Clinically, the patients with FCCFL suffered from clear nasal fluid flow, ear tightness, and hearing loss. On CT, all of the affected ears were depicted markedly dilatation of the proximal portion of fallopian canal(FC), the labyrinthine segment and geniculate fossa were involved in 4 cases, and involvement of tympanic segment in 1 case at the same time. The geniculate fossa in the affected side were significantly enlarged, protruding upwards into the tympanic cavity, with one case simultaneously involving the cochlea. On MRI, the hyposignal on T1WI and hypersignal on T2WI or water sequence like cerebrospinal fluid (CSF) were shown in the enlargement FC, without diffusion restriction, and non-enhancing with administration Gadolinium contrast.CSF-like signal effusion was shown in all of the affected tympanum, of which, the CSF-like signal effusion was demonstrated in the area along the superficial petrosal nerve, the right pterygopalatine fossa and the parapharyngeal space. The adjacent intracranial meninges were presented thickening in 3 cases. Conclusion: The imaging appearances of FCCFL present some characteristics:on HRCT, the proximal portions of the affected FC depicts markedly enlargement,especially the geniculate fossa.While they present CSF-like signal, no diffusion restriction, and no enhancement administration, Gadolinium contrast on MRI, accompanying the CSF-like signal effusion in the affected tympanum.

[Disease burden and prediction of oral cancer attributable to smoking in China from 1990 to 2019].

Objective: To analyze the trend of disease burden of oral cancer attributable to smoking in China from 1990 to 2019, and predict the mortality trend of oral cancer from 2020 to 2034, providing scientific basis for formulating targeted oral cancer prevention and treatment strategy to achieve the goal of "Healthy China 2030". Methods: Using partial data on the global burden of disease in China in 2019, attributive death and disability adjusted life year (DALY) were used to describe. The trend of changes in the burden of oral cancer disease attributed to smoking was analyzed by using the Joinpoint regression model to estimate the annual average percentage change (AAPC) of age standardized mortality and DALY rates. Meanwhile, the Bayesian age-period- cohort model is used to predict oral cancer deaths and DALY trends attributed to smoking over the next 15 years. Results: The age-standardized mortality rate and DALY rate in China from 1990 to 2019 showed an overall upward trend, with an average annual increase of 1.49% (95%CI: 1.34%-1.65%, P<0.001) and 1.41% (95%CI: 1.24%-1.59%, P<0.001) respectively, higher than around the earth and in regions with different socio-demographic index (SDI). In 2019, 46.74% (10 584/22 642) of oral cancer deaths in China were attributed to smoking. Compared to 1990, the number of attributed deaths in 2019 increased by 293.75% (7 896/2 688), while DALY increased by 257.97% (189 039/73 280). Moreover, the growth rates of attributed deaths and DALY in males [304.95% (7 584/2 487) and 265.60% (183 349/69 033), respectively] were significantly higher than those in females [154.73% (311/201) and 133.95% (5 690/4 248), respectively] (P<0.001). The age group results showed that the proportion of deaths and DALY gradually transitioned towards the elderly (>60 years old). The expected number of deaths would increase from 10 731 in 2020 to 14 125 in 2034, with a rise of 31.63% (3 394/10 731). Simultaneously, DALY would increase from 267 064 person years in 2020 to 326 634 person years in 2034, with a rise of 22.31% (59 570/267 064). Conclusions: From 1990 to 2019, the burden of oral cancer diseases attributed to smoking in China showed an increasing trend, with a higher growth rates than in the global and different SDI regions. There were differences in gender and age, and the burden of oral cancer diseases attributed to smoking in China would continue to increase in the next 15 years. It is necessary to educate on the adverse effects of tobacco consumption and to conduct vigilant oral self-examination among high-risk groups to help early detection and intervention at the same time.

Salvage camrelizumab for an intractable NK/T cell lymphoma patient with two instances of intestinal perforation: a case report and literature review.

BACKGROUND: The prognosis of natural killer/T cell lymphoma (NKTCL) with multifocal small intestine involvement complicated by intestinal perforation is extremely poor. There is no evidence-based treatment strategy for this intractable condition. CASE PRESENTATION: A 30-year-old male was admitted to our hospital in April 2017 and presented with recurrent fever for three months and multiple painless subcutaneous nodules in the abdominal wall. An excision biopsy of the subcutaneous nodules in the abdominal wall revealed NKTCL. The patient was diagnosed with stage IVB NKTCL with skin and multifocal small intestinal involvement according to the imaging results. The first intestinal perforation occurred due to tumor infiltration before the initial treatment. The second intestinal perforation occurred after receiving two cycles of chemotherapy with a modified SMILE regimen. The histone deacetylase inhibitor (HDACi) chidamide was administered as a single-agent therapy after recovery from the second intestinal perforation. Complete remission was achieved. Unfortunately, five months later, the patient was confirmed to have relapsed and received the salvage chemotherapy. The patient suffered from disease progression again after the fourth cycle of chemotherapy. At this point, from May 29, 2018, the patient started to receive injections of the anti-programmed death 1 (PD-1) antibody camrelizumab as a salvage treatment. Two months after the initial anti-PD-1 antibody camrelizumab injection, the response was partial remission. Disease progression was confirmed in March 2021, with a progression-free survival time of 34 months. CONCLUSIONS: NKTCL patients with multifocal small intestine involvement have a high risk of intestinal perforation. The possible etiologies of bowel perforation include tumor infiltration, tumor necrosis in response to therapy, and acute inflammation. The anti-PD-1 antibody camrelizumab may be a new candidate agent for treating this type of intractable NKTCL. Further observations are necessary to identify the efficacy and safety of new agents in the future.

[Effects of screen exposure on language skills in children].

Objective: To investigate the association between screen exposure and language skills in children aged 2-5 years. Methods: There were 299 children aged 2-5 years, recruited by convenience sampling from those who visited the Center of Children's Healthcare, Children's Hospital, Capital Institute of Pediatrics for routine physical examination from November 2020 to November 2021. Their development status were evaluated by the children neuropsychological and behavioral scale (revision 2016). A self-designed questionnaire for parents was conducted to collect demographic and socioeconomic information and screen exposure characteristics (time and quality). One-way ANOVA and independent sample t test were applied to compare the differences in language development quotient of children with different screen exposure time and quality. Multiple linear regression was used to analyze the correlation between screen exposure time and quality with language developmental quotient. Multivariate Logistic regression was used to analyze the risk of language underdevelopment in children with different screen exposure time and quality. Results: Among 299 children, 184 (61.5%) were boys and 115 (38.5%) were girls, with the age of (3.9±1.1) years. The number of children with daily screen time <60, 60-120 and>120 min was 163 children (54.5%), 86 children (28.8%) and 50 children (16.7%), respectively, with the language development quotients of 94±13, 90±13, 84±14, respectively, demonstrating a statistically significant difference (F=8.92, P<0.001). Logistic regression analysis revealed that screen exposure time of 60-120 and >120 min per day were both risk factors for children's language developmental quotients (OR=2.28, 95%CI 1.00-5.17, P=0.043; OR=3.96, 95%CI 1.86-9.17, P<0.001), and co-viewing and exposure to educational programs were both protective factors for children's language developmental quotients (OR=0.48, 95%CI 0.25-0.91, P=0.024, OR=0.36, 95%CI 0.19-0.70, P=0.003). Conclusions: Excessive exposure screen time and inappropriate screen exposure habits are associated with children's poorer language development. Screen exposure time should be limited and screen use should be rational to promote children's language skills.

Inversion models of aboveground grassland biomass in Xinjiang based on multisource data.

Grassland biomass monitoring is essential for assessing grassland health and carbon cycling. However, monitoring grassland biomass in drylands based on satellite remote sensing is challenging.Statistical regression models and machine learning have been used for the construction of grassland biomass models, but the predictive power for different grassland types is unclear. Additionally, the selection of the most appropriate variables to construct a biomass inversion model for different grassland types must be explored. Therefore,1201 ground-truthed data points collected from 2014-2021,including 15 Moderate Resolution Imaging Spectroradiometer (MODIS) vegetation indices,geographic location and topographic data,and meteorological factors and vegetation biophysical indicators were screened for key variables using principal component analysis (PCA). The accuracy of multiple linear regression models, exponential regression models, power function models, support vector machine (SVM) models, random forest (RF) models, and neural network models was evaluated for the inversion of three types of grassland biomass. The results were as follows: (1) The biomass inversion accuracy of single vegetation indices was low, and the optimal vegetation indices were the soil-adjusted vegetation index (SAVI) (R2 = 0.255), normalized difference vegetation index (NDVI) (R2 = 0.372) and optimized soil-adjusted vegetation index (OSAVI) (R2 = 0.285). (2)Grassland above-ground biomass (AGB) was affected by various factors such as geographic location,topography, and meteorological factors, and the inverse models using a single environmental variable had large errors. (3) The main variables used to model biomass in the three types of grasslands were different. SAVI, aspect, slope, and precipitation (Prec.) were selected for desert grasslands; NDVI,shortwave infrared 2 (SWI2), longitude, mean temperature, and annual precipitation were selected for steppe;and OSAVI, phytochrome ratio (PPR), longitude, precipitation, and temperature were selected for meadows. (4) The non-parametric meadow biomass model was superior to the statistical regression model. (5) The RF model was the best model for the inversion of grassland biomass in Xinjiang, and this model had the highest accuracy for grassland biomass inversion (R2 = 0.656, root mean square error (RMSE) = 815.6 kg/ha),followed by meadow (R2 = 0.610, RMSE = 547.9 kg/ha) and desert grassland (R2 = 0.441, RMSE = 353.6 kg/ha).

[Analysis of neuropsychological development characteristics and influencing factors in children with speech sound disorder].

Objective: Exploring the neuropsychological developmental characteristics and influencing factors of children with speech disorder. Methods: A case-control study was conducted. A total of 395 children diagnosed with speech disorders were selected as speech sound disorder (SSD) group from January 2019 to September 2021 in the speech-speech outpatient department of the Children's Hospital Affiliated to Capital Institute of Pediatrics, and 1 179 healthy children who underwent physical examination in the health department during the same period were selected as the control group. All the children were examined by the "Children's Neuropsychological Behavior Scale 2016 Edition" (Children's Mind Scale 2016 edition). Independent sample t test was used to compare the developmental levels of the two groups of children, including total developmental quotient, gross motor, fine motor, adaptive ability, language and social behavior ability. The influential factors of children's speech disorders were analyzed by univariate Chi-square analysis and multivariate logistic regression. Results: There were 395 SSD children, including 296 males and 99 females, 4≤ age ≤6, (4.71±0.76) years. There were 1 179 children in the control group, including 864 males and 315 females, 4≤ age ≤6, (4.64±0.78) years. The mean value of total developmental factors in SSD group was lower than that in control group [(86.45±11.57)/(91.24±8.0), t=-7.78, P<0.01], and the mean values of total developmental markers in both boys and girls in SSD group were lower than those in control group [(86.00±11.40)/(90.78±7.86), t=-6.70, P<0.01; (87.82±12.03)/(92.87±8.49), t=-3.88, P<0.01]. The mean values of gross motor, fine motor, adaptive ability, language ability and social behavior in SSD group were lower than those in control group [(89.76±12.47)/(92.01±10.69), t=-3.21, P<0.01; (80.62±13.64)/(84.49±11.55), t=-5.06, P<0.01; (87.92±15.25)/(92.98±12.06), t=-6.00, P<0.01; (86.48±16.30)/(94.55±12.08), t=-9.04, P<0.01; (87.02±15.18)/(92.63±12.57), t=-6.62, P<0.01]; The mean value of fine motor in boys was lower than that in girls in SSD group [(79.80±13.42)/(83.08±14.05), t=-2.08, P<0.05]. Independent mealtimes. 2 years old (OR=1.527, 95%CI: 1.180-1.977, P=0.001), delay in adding supplemental food (OR=1.510, 95%CI: 1.123-2.029, P=0.006), dialect in the home language environment (OR=1.351, 95%CI: 1.060-1.723, P=0.015) were risk factors for children with speech disorders. Conclusion: Children with speech disorders are more common in boys. The overall development level of SSD children is lower than that of normal children, and the fine motor of SSD boys is lower than that of girls. The incidence of children's speech disorders is related to the addition time of supplementary food, independent meal time and family language environment.

[Evaluation of the clinical manifestations of COVID-19 in patients with aplastic anemia undergoing immunosuppressive therapy: a prospective cohort study (NICHE)].

Objective: To investigate the clinical features of coronavirus disease 2019 (COVID-19) in patients with aplastic anemia (AA) undergoing immunosuppressive therapy (IST) . Methods: In this prospective cohort study, we collected the demographic and clinical data of patients with AA and COVID-19 from December 1, 2022, to January 31, 2023. We described the clinical features of COVID-19 among patients with AA and evaluated the effects of IST on the signs and severity of COVID-19. Results: A total of 170 patients with AA and COVID-19 were included. The common early symptoms, including fever, dizziness or headache, muscle or body aches, and sore throat, disappeared within 1-2 weeks. Approximately 25% of the patients had persistent fatigue within 2 weeks. Many patients experienced cough after an initial 1-3 days of infection, which lasted for more than 2 weeks. There were no differences in the duration of total fever episodes and maximum body temperature when patients were stratified according to whether or not they underwent IST, by IST duration, or by use of anti-lymphocyte globulin (ALG) (P>0.05). No differences were observed in the occurrence of symptoms in either the early or recovery stages when patients with AA were stratified according to whether or not they underwent IST, or by IST duration (P>0.05). However, patients who received ALG had fewer fever episodes within 1 week after infection (P=0.035) and more sore throat episodes within 2 weeks after infection (P=0.015). There were no other significant differences in clinical symptoms between patients who did and patients who did not receive ALG (P>0.05) . Conclusion: The majority of patients with AA and COVID-19 recovered within 2 weeks of noticing symptoms when treated with IST.

[Significance of triggering receptor expressed on myeloid cells-2 prognostic evaluation in hepatitis B virus-related acute-on-chronic liver failure].

Objective: To explore the significance of triggering receptor expressed on myeloid cells-2 (TREM-2) prognostic evaluation so as to provide novel biological markers in clinical practice for patients with hepatitis B virus-related acute-on-chronic liver failure ( HBV-ACLF). Methods: The research subjects of this study were divided into an experimental group and a control group. Fifty HBV-ACLF cases admitted to the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 1, 2019 to December 31, 2019 were selected as the experimental group. Patients were divided into survival and death groups according to the actual prognosis at discharge (self-discharge and dead patients were considered death groups, and all enrolled patients were hospitalized for more than 28 days). Twenty-five healthy subjects were chosen as the control group. Peripheral venous blood was collected from the experimental group and the control group. Plasma and peripheral blood mononuclear cells (PBMC) were isolated. The concentrations of TREM-2, interleukin (IL)-6, and IL-8 were detected in the plasma. TREM-2 mRNA expression was detected in PBMC. A single blood sample was collected from the control group, whereas five blood samples were dynamically collected from the experimental group on the day of admittance and at 7, 14, 21, and 28 days after treatment commenced. Simultaneously, upon admission, the relevant clinical indicators of HBV-ACLF patients were monitored, including the liver function test: alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, coagulation function test: international normalized ratio, prothrombin time, and other indicators. Measurement data were expressed as mean±standard deviation (x±s). Count data were compared and analyzed using the χ(2) test. The intra-group factor mean was compared using a repeated measures ANOVA. The means were analyzed by t-tests between the two groups. Bivariate correlation analysis was used to analyze the correlation between the two variables. The value of TREM-2 as a diagnostic marker was analyzed using the receiver operating characteristic (ROC) curve. Results: The mRNA expression of TREM-2 in the PBMC of HBV-ACLF patients showed a gradually increasing trend at various time points and was significantly higher in the survival group than that of the control group at 28 days (P < 0.01), while the death group showed a gradually weakening trend at various time points and was significantly lower than the control group at 28 days (P < 0.01). (1) The levels of TREM-2 in the plasma of HBV-ACLF patients generally showed a gradually increasing trend at various time points in the survival group. The levels on the day of admission and 7, 14, 21, and 28 days after the initiation of treatment were (1.49±0.85), (1.62±0.58), (1.95±0.69), (2.33±0.71), and (2.00±0.67) ng/ml, respectively. The expression of TREM-2 in the death group showed a gradually weakening trend at various time points. The levels on the day of admission and 7, 14, 21, and 28 days after initiation of treatment were (1.40±0.73), (1.59±0.79), (1.56±0.80), (1.05±0.49), and (0.81±0.21) ng/ml, respectively. The survival group's various detection time points were higher than those of the death group, and the difference was statistically significant. The plasma level of TREM-2 in the healthy control group was (1.25±0.35) ng/ml. (2) The concentrations of IL-6 and IL-8 in the plasma of HBV-ACLF patients showed a gradually decreasing trend at various time points in the survival group. The levels on the day of admission and 7, 14, 21, and 28 days after initiation of treatment were (46.70±26.31), (33.98±20.28), (19.07±10.24), (14.76±7.84), (9.12±7.65) and (108.29±47.07), (93.85±26.53), (79.27±34.63), (56.72 ±18.30), (37.81±13.88) pg/ml, respectively. However, its concentration in the death group fluctuated within a relatively high range. The levels on the day of admission and 7, 14, 21, and 28 days after the initiation of treatment were (41.94±24.19), (36.99±19.78), (34.30±20.62), (34.14±14.52), (36.64±23.61) and (104.65±50.16), (112.98±45.03), (118.43±45.00), (111.67±40.44), (109.55±27.54) pg/ml, respectively. (3) Bivariate correlation analysis results indicated that the plasma TREM-2 content was negatively correlated with the plasma levels of pro-inflammatory cytokines IL-6 and IL-8 (r = -0.224, P = 0.025; r = - 0.223, P = 0.026). ROC curve analysis showed that the mRNA levels of TREM-2 in PBMCs at various time points for prognostic evaluation of HBV-ACLF patients were 1d=0.667, 7d=0.757, 14d=0.979, 21d=0.986, and 28d= 0.993. The areas under the ROC curve of the TREM-2 content in the plasma at various time points were 1d=0.522, 7d=0.571, 14d=0.658, 21d=0.927, and 28d=0.994. Conclusion: TREM-2 mRNA expression in PBMC and TREM-2 content in plasma have a significant relationship to the prognosis of HBV-ACLF patients and may inhibit the liver inflammatory response by regulating the secretion of pro-inflammatory cytokines IL-6 and IL-8. Dynamic monitoring of TREM-2 expression in peripheral blood is favorable for evaluating the prognostic condition of HBV-ACLF patients.

[Clinical application of laparoscopic sentinel lymph node mapping in early staged cervical cancer].

Objective: To investigate the application of sentinel lymph node biopsy (SLNB) in early-staged cervical cancer by laparoscopy. Methods: It was a prospective, single-arm, single-center clinical study. Seventy-eight cases of cervical cancer patients were collected from July 2015 to December 2018 at the Fourth Hospital of Hebei Medical University. All the patients were injected with tracer into the disease-free block of cervical tissue after anesthesia by the same surgeon who learned sentinel lymph node (SLN) mapping technique in Memorial Sloan-Kettering Cancer Center, and underwent SLN mapping followed by complete pelvic lymphadenectomy. Moreover, all the dissected lymph nodes were stained with hematoxylin eosin staining (HE) pathological examination. Besides, the negative SLN on hematoxylin-eosin staining were detected by immunohistochemistry cytokeratin staining micro-metastasis. To analyze the distribution, detection rate, false negative rate the sensitivity and negative predictive value of the SLN in early-staged cervical cancer by laparoscopy, and explore the value of SLN mapping in predicting the lymph nodes metastasis in early-staged cervical cancer. Results: The overall detection rate of SLN in cervical cancer was 99% (77/78), bilateral detection rate was 87% (68/78). The average of 12.4 lymph node (LN) and 3.6 SLN were dissected for each patients each side. SLN of cervical cancer were mainly distributed in the obturator space (61.5%, 343/558), followed by external iliac (23.5%, 131/558), common iliac (7.3%, 41/558), para-uterine (3.8%, 21/558), internal iliac (2.2%, 12/558), para abdominal aorta (1.1%, 6/558), and anterior sacral lymphatic drainage area (0.7%, 4/558). Fourteen cases of LN metastasis were found among all 78 cases. There were a total of 38 positive LN, including 26 SLN metastasis and 12 none sentinel LN metastasis. Through immunohistochemical staining and pathological ultra-staging, 1 SLN was found to be isolated tumor cells (ITC), and 5 SLNs were found to be micro-metastases (MIC), accounting for 23% (6/26) of positive SLN. SLN mapping with pathological ultra-staging improved the prediction of LN metastasis in cervical cancer (2/14). Metastatic SLN mainly distributed in the obturator space (65%, 17/26), peri-uterine region (12%, 3/26), common iliac region (15%, 4/26), and external iliac region (8%, 2/26). The consistency of the diagnosis of lymph node metastasis by SLN biopsy and postoperative retroperitoneal lymph node metastasis showed that the Kappa value was 1.000 (P<0.001), indicated that the metastasis status of SLN and retroperitoneal lymph node were completely consistent. The sensitivity, specificity, accuracy, false-negative rate, and negative predictive value of SLN biopsy in the diagnosis of lymph node metastasis were 100%, 100%, 100%, 0, and 100%, respectively. Conclusions: SLN in early-staged cervical cancer patients were mainly distributed in the obturator and external iliac space, pathalogical ultra-staging of SLN could improve the prediction of LN metastasis. Intraoperative SLN mapping is safe, feasible and could predict the state of retroperitoneal LN metastasis in early-staged cervical cancer. SLNB may replace systemic pelvic lymphadenectomy.

Decoding drug resistant mechanism of V32I, I50V and I84V mutations of HIV-1 protease on amprenavir binding by using molecular dynamics simulations and MM-GBSA calculations.

Mutations V32I, I50V and I84V in the HIV-1 protease (PR) induce drug resistance towards drug amprenavir (APV). Multiple short molecular dynamics (MSMD) simulations and molecular mechanics generalized Born surface area (MM-GBSA) method were utilized to investigate drug-resistant mechanism of V32I, I50V and I84V towards APV. Dynamic information arising from MSMD simulations suggest that V32I, I50V and I84V highly affect structural flexibility, motion modes and conformational behaviours of two flaps in the PR. Binding free energies calculated by MM-GBSA method suggest that the decrease in binding enthalpy and the increase in binding entropy induced by mutations V32I, I50V and I84V are responsible for drug resistance of the mutated PRs on APV. The energetic contributions of separate residues on binding of APV to the PR show that V32I, I50V and I84V highly disturb the interactions of two flaps with APV and mostly drive the decrease in binding ability of APV to the PR. Thus, the conformational changes of two flaps in the PR caused by V32I, I50V and I84V play key roles in drug resistance of three mutated PR towards APV. This study can provide useful dynamics information for the design of potent inhibitors relieving drug resistance.

[The risk factors of distal aorta negative remodeling after endovascular aortic repair in type B dissection].

In recent years, great progress has been made in the treatment of Stanford type B aortic dissection, especially endovascular repair technology has become the main treatment. However, it is only used to repair the primary tear, the residual tears and false lumen are often left at the distal end, which causes adverse events such as distal aortic dilatation or even rupture. At present, there are many studies on the influencing factors of aortic remodeling, which provide some references for the prognosis of patients.The aorta carries the transportation of blood flow, and various factors affecting hemodynamics also affect the remodeling of aorta. Some researchers reported several factors related to negative remodeling and added auxiliary techniques, and achieved gratifying results. However, because of the different conditions of each patient, the specific treatment method is still unclear, the factors affecting the aortic remodeling effect also have not been thoroughly studied. Clarifying the influencing factors of negative remodeling is helpful to screen high-risk patients, optimize the treatment plan and improve the prognosis.

An approach combining bioinformatics and machine learning to identify eight autophagy-related biomarkers and construct molecular mechanisms underlying COVID-19 and major depressive disorders.

OBJECTIVE: A lack of objective biomarkers is preventing the screening and diagnosis of COVID-19 combined with major depression disorder (COVID-19-MDD). The purpose of this study was to identify diagnostic biomarkers and gene regulatory mechanisms associated with autophagy; a crucial process significantly involved in the pathogenesis of COVID-19-MDD. MATERIALS AND METHODS: In this study, differentially expressed genes (DEGs) were screened using GSE98793 from the GEO2R analysis (GEO) database, and intersected with the COVID-19-related gene (CRGs) and autophagy-related genes (ARGs) to obtain common genes involved in. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these common genes were performed. Subsequently, the transcription factor (TF)-gene regulatory network and comorbidity network were constructed. In addition, 10 drug candidates were screened using the DSigDB database. To identify diagnostic markers, we used LASSO regression. RESULTS: In total, 13 common genes were screened, which were primarily enriched in lysosomes, endoplasmic reticulum membranes, and other endomembrane systems also associated with autophagy. Additionally, these genes were involved in neurological cell signaling and have a functional role in pathways related to vascular endothelial growth factor, tyrosine kinase, autophagy, inflammation, immunity, and carcinogenesis. Tumors and psychiatric disorders were the most highly linked diseases to COVID-19. Finally, ten drug candidates and eight diagnostic markers (STX17, NRG1, RRAGD, XPO1, HERC1, HSP90AB1, EPHB2, and S1PR3) were screened. CONCLUSIONS: This is the first study to screen eight diagnostic markers and construct a gene regulatory network for COVID-19-MDD from the perspective of autophagy. The findings of our study provide novel insights into the diagnosis and treatment of COVID-19-MDD.

[Preclinical study of T cell receptor specifically reactive with KRAS G12V mutation in the treatment of malignant tumors].

OBJECTIVE: KRAS gene is one of the most common mutations of proto-oncogenes in human tumors, G12V is one of the most common mutation types for KRAS. It's challenging to chemically acquire the targeted drug for this mutation. Recent studies reported that this mutation peptides can form a neoepitope for T cell recognition. Our study aims to clone the T cell receptor (TCR) which specifically recognizes the neoepitope for KRAS G12V mutation and constructs TCR engineered T cells (TCR-T), and to investigate if TCR-Ts have strong antitumor response ability. METHODS: In this study, tumor infiltrating lymphocytes were obtained from one colorectal cancer patient carrying KRAS G12V mutation. Tumor-reactive TCR was obtained by single-cell RT-5' rapid-amplification of cDNA ends PCR analysis and introduced into peripheral blood lymphocytes to generate TCR-Ts. RESULTS: We obtained a high-affinity TCR sequence that specifically recognized the HLA-A*11:01-restricted KRAS G12V8-16 epitope: KVA11-01. KVA11-01 TCR-T could significantly kill various tumor cells such as PANC-1, SW480 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V), and secreting high levels of interferon-γ (IFN-γ). Non-specific killing experiments suggested KVA11-01 specifically recognized tumor cells expressing both mutant KRAS G12V and HLA-A*11:01. In vivo assay, tumor inhibition experiments demonstrated that infusion of approximately 1E7 KVA11-01 TCR-T could significantly inhibit the growth of subcuta-neously transplanted tumors of PANC-1 and HeLa (overexpressing HLA-A*11:01 and KRAS G12V) cells in nude mice. No destruction of the morphologies of the liver, spleen and brain were observed. We also found that KVA11-01 TCR-T could significantly infiltrate into tumor tissue and had a better homing ability. CONCLUSION: KVA11-01 TCR-T cells can effectively target a variety of malignant tumor cells carrying KRAS G12V mutation through in vitro and in vivo assay. KVA11-01 TCR-T cells have excellent biological activity, high specificity of target antigen and homing ability into solid tumor tissue. KVA11-01 TCR-T is expected to be an effective treatment for patients with KRAS G12V mutant solid malignancies.

[Clinical efficacy evaluation of minimally invasive cardiac surgery coronary artery bypass grafting in patients with multivessel coronary artery disease].

Objective: To investigate the clinical efficacy of minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) in the treatment of patients with multivessel coronary artery disease. Methods: A total of 147 patients with multi-vessel coronary artery disease and coronary heart disease who underwent surgical treatment in Henan Provincial People's Hospital from March 2016 to March 2019 were retrospectively selected. Of which, 69 patients were treated by MICS CABG (minimally invasive group) and 78 patients were treated using the traditional thoracotomy (traditional group). The perioperative indexes, serum myocardial enzyme indexes and renal function indexes of patients before and after operation were compared between the two groups; Two groups of patients were followed up for 2 years; the incidence of adverse cardiovascular events (MACE) was recorded, and survival analysis was performed. Results: The age of the patients in the minimally invasive group and the traditional group were (66.9±5.8) and (68.2±7.0) years old, respectively, and the proportions of males were 60.9% (42 cases) and 51.3% (40 cases) (all P>0.05). All patients in the two groups successfully completed the operation, and no patients in the minimally invasive group were converted to thoracotomy. Before surgery, there was no significant difference in serum cTnI, CK-MB, BUN, Scr, and creatinine clearance between the minimally invasive group and the traditional group (all P>0.05). After re-examination 48 hours after operation, the serum cTnI in the minimally invasive group was (3.109±0.664) µg/L, and the CK-MB was (18.03±3.27) U/L, which were lower than those in the traditional group (3.438±0.715) µg/L, (20.63±4.28) U/L; the difference was statistically significant (all P<0.05). During the 2-year follow-up, there was no statiscally significant difference in the incidence of recurrent myocardial infarction, postoperative atrial fibrillation, postoperative stroke, arrhythmia, heart failure, thrombosis, cardiac death, and MACE events between the minimally invasive group and the traditional group. Statistical significance (all P>0.05). The survival curve analysis showed that the cumulative rates of MACE events in the minimally invasive and traditional groups were 17.39% and 26.92%, respectively (P=0.171). Conclusions: The effect of MICS CABG in the treatment of patients with multivessel coronary artery disease and coronary heart disease is not much different from that of traditional open thoracotomy, but the former is less traumatic, quicker after surgery, and has clinical significance for the recovery of patients' myocardial function.