Objective:To investigate the expression of KCTD8 gene in breast ductal carcinoma and its correlation with clinical factors and prognosis.Methods:Immunohistochemistry technology(IHC)were employed to detect protein expression levels of KCTD8 in 27 pairs of breast ductal carci-noma and its paired adjacent tissues.Analyzing the correlation between changes in KCTD8 expres-sion of protein and clinical factors using statistical techniques.RNA expression and methylation data of breast cancer(including intraductal cancer)were analysed from TCGA database.Result:The pro-tein expression of KCTD8 gene in 27 pairs of breast ductal carcinoma tissues showed a decreasing trend compared to adjacent tissues(P＜0.05),and the decreased expression level of protein was cor-related with the tumor size of patients(P＜0.05).The analysis results of the TCGA database indicate that the expression and hypemethylation of KCTD 8 gene in breast cancer(including intraductal can-cer)tissues affected the prognosis of patients.Conclusion:The reduced protein expression level of KCTD8 gene in breast ductal carcinoma may be involved in the development and affect the prog-nosis of patients.

Purpose: The association between immune-related adverse events (irAEs) and survival outcomes in non–small cell lung cancer (NSCLC) patients treated with programmed death-(ligand) 1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB). Materials and Methods: We retrospectively enrolled 425 advanced NSCLC patients who received anti–PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAE (n=127) and non-irAE (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark (2-, 3-, 6-, and 9-month) and time-dependent Cox analyses were performed to eliminate ITB. Results: With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs. 3.4 months, p < 0.001) and OS (31.4 vs. 14.0 months, p < 0.001), which persisted in landmark and time-dependent Cox analyses. For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid, and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival. Conclusion After adequately adjusting ITB, the occurrence of overall irAEs predicts for favorable efficacy of anti–PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.

Objective: To investigate the epidemiological characteristics of human adenovirus (HADV) 2, 3 and 7 in hospitalized children with respiratory infection. Methods: A total of 25 686 children with respiratory infection hospitalized at Children's Hospital of Hebei Province from January 2018 to December 2020 were retrospectively included.Deep sputum or nasopharyngeal aspirates of those children were collected. Then thirteen common respiratory pathogens were detected by multiplex PCR. 510 HADV positive specimens were randomly selected via random number and classified for type 2, 3 and 7 using a multiplex real-time quantitative PCR. SPSS 21.0 software was used to perform all of the statistical analyses. Enumeration data were expressed by frequency and percentage. χ² test was used for comparison between groups. Results: The HADV-positive rate was 7.99% (2 052/25 686). Children at age 3-<6 years had the highest HADV-positive rate (11.44%). The HADV-positive rate in 2019 was highest (10.64%). Among the 510 HADV-positive specimens, the proportion of type 3 was the highest (31.16%), followed by type 7 (21.37%) and type 2 (11.18%). The rate of type 2 in 2019 was significantly lower than that in 2018 and 2020 (χ²=8.954 and 16.354; P=0.003 and <0.01), while the rate of type 3 was significantly higher than that in 2018 and 2020 (χ²=5.248 and 4.811; P=0.022 and 0.028). The rate of type 2, type 3 and type 7 were lowest in winter, spring and autumn, respectively. The rate of type 2 increased significantly in autumn and the rate of type 3 and type 7 increased significantly in winter.The co-detection rate of HADV with other respiratory pathogens was 43.33%(221/510). Among, the co-detection rate of type 3 was highest (47.32%), and the co-detection rate of type 2, 3 and 7 was significantly higher than the alone detection rate (χ²=20.438, P<0.01; χ²=42.105, P<0.01; χ²=27.573, P<0.01).The proportion of severe pneumonia in children with type 7 positive (15.89%) was higher than that in children with non-type 7 positive (8.23%) (χ²=5.260, P=0.022). Conclusion: HADV is one of the important pathogens of children with respiratory infection in Children's Hospital of Hebei Province. The susceptible population of HADV is preschool children aged 3 to 6 years. HADV often co-detects with other respiratory pathogens. Type 3 and 7 is likely to be the dominant genotypes in this region, and type 7 may be one of the risk factors of severe pneumonia in children.
Child, Preschool ; Child ; Humans ; Infant ; Adenoviruses, Human/genetics* ; Child, Hospitalized ; Retrospective Studies ; Adenovirus Infections, Human/epidemiology* ; Respiratory Tract Infections/epidemiology* ; Pneumonia ; Hospitals

Objective: To establish a predictive model for survival benefit of patients with intrahepatic cholangiocarcinoma (ICC) who received adjuvant chemotherapy after radical resection. Methods: The clinical and pathological data of 249 patients with ICC who underwent radical resection and adjuvant chemotherapy at 8 hospitals in China from January 2010 to December 2018 were retrospectively collected. There were 121 males and 128 females,with 88 cases>60 years old and 161 cases≤60 years old. Feature selection was performed by univariate and multivariate Cox regression analysis. Overall survival time and survival status were used as outcome indicators,then target clinical features were selected. Patients were stratified into high-risk group and low-risk group,survival differences between the two groups were analyzed. Using the selected clinical features, the traditional CoxPH model and deep learning DeepSurv survival prediction model were constructed, and the performance of the models were evaluated according to concordance index(C-index). Results: Portal vein invasion, carcinoembryonic antigen>5 μg/L,abnormal lymphocyte count, low grade tumor pathological differentiation and positive lymph nodes>0 were independent adverse prognostic factors for overall survival in 249 patients with adjuvant chemotherapy after radical resection (all P<0.05). The survival benefit of adjuvant chemotherapy in the high-risk group was significantly lower than that in the low-risk group (P<0.05). Using the above five features, the traditional CoxPH model and the deep learning DeepSurv survival prediction model were constructed. The C-index values of the training set were 0.687 and 0.770, and the C-index values of the test set were 0.606 and 0.763,respectively. Conclusion: Compared with the traditional Cox model, the DeepSurv model can more accurately predict the survival probability of patients with ICC undergoing adjuvant chemotherapy at a certain time point, and more accurately judge the survival benefit of adjuvant chemotherapy.

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Objective: To analyze the survival and influencing factors of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) . Methods: Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and leukemia-free survival (LFS) times of patients, and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy. Results: Among the 38 patients with R/R B-ALL, 21 were men, with a median age of 25 (6-59) years and a median OS time of 18 (95% CI 3-33) months. Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS (OS: HR=4.888, 95% CI 1.375-17.374, P=0.014; LFS: HR=6.683, 95% CI 1.815-24.608, P=0.004). Maintenance therapy was a protective factor for OS and LFS (OS: HR=0.153, 95% CI 0.054-0.432, P<0.001; LFS: HR=0.138, 95% CI 0.050-0.382, P<0.001). In patients with MRD negative conversion, LFS benefit (HR=0.209, 95% CI 0.055-0.797, P=0.022) and OS difference was statistically insignificant (P=0.111). Moreover, patients with high tumor burden were risk factors for OS and LFS at the level of 0.1 (OS: HR=2.662, 95% CI 0.987-7.184, P=0.053; LFS: HR=2.452, 95% CI 0.949-6.339, P=0.064) . Conclusion: High tumor burden and high-risk genetics may affect the long-term survival rate of patients with R/R B-ALL receiving CAR-T, and lenalidomide-based maintenance therapy may improve their prognosis.
Male ; Humans ; Adult ; Middle Aged ; Female ; Receptors, Chimeric Antigen/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Immunotherapy, Adoptive ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Cell- and Tissue-Based Therapy

Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.
Drugs, Chinese Herbal ; Analytic Hierarchy Process ; Berberine ; Entropy ; Water

Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion (0.158 2),perineural invasion (0.158 2),N stage (0.155 8),T stage (0.120 9), hepatic envelope invasion (0.090 3),adjuvant chemotherapy (0.072 1), tumor location (0.057 5), age (0.042 3), pathological differentiation (0.034 0), sex (0.029 3), alpha-fetoprotein (0.028 9) and preoperative jaundice (0.008 5). A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase in the probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.
Bayes Theorem ; Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; Chemotherapy, Adjuvant ; Cholangiocarcinoma/surgery* ; Female ; Humans ; Male ; Prognosis ; Retrospective Studies

OBJECTIVE: To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy. METHODS: A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted. RESULTS: In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P<0.05 or P<0.01); the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group (P<0.05). There was no significant difference in the incidence of anal stenosis, the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation (P>0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period. CONCLUSION HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883).

Objective:To investigate the long-term effects of porcine small intestinal submucosa (SIS) biologic mesh in open Lichtenstein tension-free hernia repair.Methods:The prospective randomized controlled study was conducted. The clinical data of 76 patients with unilateral inguinal hernia who underwent open Lichtenstein tension-free hernia repair in 2 medical centers (52 cases in Tianjin People′s Hospital and 24 cases in China-Japan Friendship Hospital) from August 2013 to March 2014 were selected. Based on random number method, patients were allocated into two groups. Patients undergoing Lichtenstein tension-free hernia repair using Biodesign Surgisis mesh were allocated into control group, and patients undergoing Lichtenstein tension-free hernia repair using SIS biologic mesh were allocated into experiment group. Observa-tion indicators: (1) grouping situations of the enrolled patients; (2) postoperative long-term effects. Follow-up was conducted using telephone interview, text message or mail to detect hernia recurrence or death due to other reasons as the end-point event of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented by M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Grouping situations of the enrolled patients: a total of 76 patients were selected for eligibility. There were 38 cases in the control group and the experiment group, respectively. The number of males and females, age, body mass index, cases with intraspinal anesthesia or local anesthesia (anesthesia method), cases with inguinal hernia on the left side or on the right side, cases classified as type Ⅰ, Ⅱ, Ⅲ, Ⅳ or Ⅴ of Gilbert classification, operation time of the control group were 35, 3, (56±15)years, (23.0±2.0)kg/m 2, 22, 16, 16, 22, 9, 16, 0, 11, 2 and (49±15)minutes, respectively. The above indicators of the experiment group were 34, 4, (54±13)years, (22.9±2.2)kg/m 2, 17, 21, 14, 24, 9, 21, 1, 7, 0, and (53±21)minutes, respectively. There was no significant difference in the above indicators between the two groups ( χ2=0.157, t=0.532, 0.367, χ2=1.317, 0.220, Z=-0.315, t=-0.765, P>0.05). (2) Post-operative long-term effects: 35 patients of the control group were followed up for (68.8±2.7)months, 4 cases of which died due to other reasons, 1 case had hernia recurrence, 1 case had chronic pain and no foreign body sensation and postoperative infection occurred. Thirty-one patients of the experiment group were followed up for (68.8±2.7)months, with no death or above complications. There was no significant difference in hernia recurrence or chronic pain between the two groups ( P>0.05). Conclusion:The long-term effects of biological mesh in open Lichtenstein tension-free hernia repair is satisfactory and there is no difference in the long-term effects between the domestic SIS biological mesh and Biodesign Surgisis mesh.