Tailored treatment of female indirect inguinal hernias by using single-port laparoscopic percutaneous internal ring suture: a comparison between children and adults.

PURPOSE: To compare the outcome of indirect inguinal hernias repaired by using single-port laparoscopic percutaneous internal ring suture (SPIRS) between the pediatric and adult females. METHODS: The medical records of females who were clinically assessed to have inguinal hernia from Oct. 2016 to May 2022 were reviewed. Patients who received laparoscopy for the diagnosis of the hernia type and customized treatment according to their hernia type were included, while those who chose other operation methods initially were excluded. The patients were divided into the adult and pediatric groups based on their age. The demographic characteristics, hernia types, operation durations, and outcomes were analyzed between these two groups. RESULTS: A total of 65 adults and 60 children were included in this study. The median age was 38 years. (range: 23-88) for group A and 3 years (range: 0.1-16) for group P. Indirect hernias were present in 85% of adults and 100% of children. All the indirect hernias were repaired by SPIRS uneventfully. Incidence of contralateral patent processus vaginalis was 24% in adults and 50% in children (p = 0.016). The average operation time was 22/46 min (one/two sides) for the adults and 9/15 min (one/two sides) for the pediatrics (p < 0.010 for both). The overall complication rates were 5.4% and 3.3% for the adult and pediatric group respectively (p = 0.106). No recurrence was observed in the pediatric group, but two adults experienced recurrence and another had chronic postoperative inguinal pain, necessitating reoperation. The mean follow-up period was 38.6 ± 15.4 months for adults and 42.8 ± 18.9 months for children (p = 0.198). CONCLUSION: Our results support that the pathogenesis of indirect inguinal hernia for the female adults is due to the non-obliteration of a congenital processus vaginalis. Tailored treatment of the female IIH by using single-port laparoscopic percutaneous internal ring suture may be an alternative for the management of female IHs.

Application of distal femoral 90° locking plate in children with supracondylar femoral fractures.

OBJECTIVE: This study aimed to assess the application value of distal femur 90° locking plate fixation for supracondylar femoral fractures (SFF) in children. PATIENTS AND METHODS: A total of 100 SFF children with or without diabetes who were enrolled in our hospital from January 2018 to January 2020 were randomized into a control group and a study group by the random number table method. The study group received distal femur locking plate fixation, and the control group adopted Kirschner wire (K wire) internal fixation. The primary outcomes of the two groups of children and the secondary outcomes of the diabetic patients were compared. RESULTS: The fracture union rate of the study group was significantly higher than that of the control group at 12 weeks, 16 weeks, 20 weeks and 24 weeks after the operation (p<0.05), while the rate showed no significant difference between the two groups at 28 weeks after the operation (p>0.05). The two groups showed similar operation time, intraoperative blood loss, intraoperative fluoroscopy time, and hospital stay (p>0.05). The study group yielded a more favorable outcome with regard to the Harris-Hip-Score (HHS) scores, HHS excellent-and-good rate, and Flynn scores satisfaction rate than the control group (p<0.001 or 0.05). The intracavitary pressure of the knee joint of the two groups presented a gradual decline with time, with remarkably lower results in the study group compared with the control group at 8 weeks and 16 weeks after the surgery (p<0.05), and differences at 24 weeks after the surgery did not come up to the statistical standard (p>0.05). Patients experienced fewer postoperative complications after locking plate fixation, as compared to those who received K wire treatment (p<0.05). Compared with the control group, the fracture union rate of diabetic children in the study group was significantly higher at 12 weeks, 16 weeks, and 20 weeks after surgery, respectively (p<0.05), while there was no significant difference between the two groups at 24 weeks and 28 weeks (p>0.05). CONCLUSIONS: The distal femur 90° locking plate fixation for diabetic children with SFF obviates the need for plate shaping and ensures firm fixation, with biomechanical design, promising efficacy, and few complications. The distal femur 90° locking plate fixation has better efficacy for children with diabetes. It shows great potential as the treatment of choice for diabetic children with SFF.

[The role of Keap1/Nrf2/HO-1 signal pathway in liver injury induced by rare earth neodymium oxide in mice].

Objective: To investigate the role of Keap1/Nrf2/HO-1 signaling pathway in liver injury induced by neodymium oxide (Nd(2)O(3)) in mice. Methods: In March 2021, forty-eight SPF grade healthy male C57BL/6J mice were randomly divided into control group (0.9% NaCl), low dose group (62.5 mg/ml Nd(2)O(3)), medium dose group (125.0 mg/ml Nd(2)O(3)), and high dose group (250.0 mg/ml Nd(2)O(3)), each group consisted of 12 animals. The infected groups were treated with Nd(2)O(3) suspension by non-exposed tracheal drip and were killed 35 days after dust exposure. The liver weight of each group was weighed and the organ coefficient was calculated. The content of Nd(3+) in liver tissue was detected by inductively coupled plasma mass spectrometry (ICP-MS). HE staining and immunofluorescence was used to observe the changes of inflammation and nuclear entry. The mRNA expression levels of Keap1, Nrf2 and HO-1 in mice liver tissue were detected by qRT-PCR. Western blotting was used to detect the protein expression levels of Keap1 and HO-1. The contents of catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were detected by colorimetric method. The contents of interleukin 1ß (IL-1ß), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determined by ELISA. The data was expressed in Mean±SD. Two-independent sample t-test was used for inter-group comparison, and one-way analysis of variance was used for multi-group comparison. Results: Compared with the control group, the liver organ coefficient of mice in medium and high dose groups were increased, and the Nd(3+) accumulation in liver of mice in all dose groups were significantly increased (P<0.05). Pathology showed that the structure of liver lobules in the high dose group was slightly disordered, the liver cells showed balloon-like lesions, the arrangement of liver cell cords was disordered, and the inflammatory exudation was obvious. Compared with the control group, the levels of IL-1ß and IL-6 in liver tissue of mice in all dose groups were increased, and the levels of TNF-α in liver tissue of mice in high dose group were increased (P<0.05). Compared with the control group, the mRNA and protein expression levels of Keap1 in high dose group were significantly decreased, while the mRNA expression level of Nrf2, the mRNA and protein expression levels of HO-1 were significantly increased (P<0.05), and Nrf2 was successfully activated into the nucleus. Compared with the control group, the activities of CAT, GSH-Px and T-SOD in high dose group were significantly decreased (P<0.05) . Conclusion: A large amount of Nd(2)O(3) accumulates in the liver of male mice, which may lead to oxidative stress and inflammatory response through activation of Keap1/Nrf2/HO-1 signal pathway. It is suggested that Keap1/Nrf2/HO-1 signal pathway may be one of the mechanisms of Nd(2)O(3) expose-induced liver injury in mice.

[Clinical and chest CT features of immune checkpoint inhibitor-related pneumonitis].

Objective: To explore the clinical and chest computed tomography (CT) features and the outcome of immune checkpoint inhibitor-related pneumonitis (CIP). Methods: Clinical and chest CT data of 38 CIP patients with malignant tumors from the Cancer Hospital, Chinese Academy of Medical Sciences between August 2017 and April 2021 were retrospectively reviewed, and the outcomes of pneumonitis were followed up. Results: The median time from the administration of immune checkpoint inhibitors (ICIs) to the onset of CIP was 72.5 days in 38 patients with CIP, and 22 patients developed CIP within 3 months after the administration of ICIs. The median occurrence time of CIP in 24 lung cancer patients was 54.5 days, earlier than 119.0 days of non-lung cancer patients (P=0.138), with no significant statistical difference. 34 patients (89.5%) were accompanied by symptoms when CIP occurred. The common clinical symptoms were cough (29 cases) and dyspnea (27 cases). The distribution of CIP on chest CT was asymmetric in 31 cases and symmetrical in 7 cases. Among the 24 lung cancer patients, inflammation was mainly distributed ipsilateral to the primary lung cancer site in 16 cases and diffusely distributed throughout the lung in 8 cases. Ground glass opacities (37 cases) and consolidation (30 cases) were the common imaging manifestations, and organizing pneumonia (OP) pattern (15 cases) was the most common pattern. In 30 CIP patients who were followed up for longer than one month, 17 cases had complete absorption (complete absorption group), and 13 cases had partial absorption or kept stable (incomplete absorption group). The median occurrence time of CIP in the complete absorption group was 55 days, shorter than 128 days of the incomplete absorption group (P=0.022). Compared with the incomplete absorption group, there were less consolidation(P=0.010) and CIP were all classified as hypersensitivity pneumonitis (HP) pattern (P=0.004) in the complete absorption group. Conclusions: CIP often occurs within 3 months after ICIs treatment, and the clinical and CT findings are lack of specificity. Radiologic features may have a profound value in predicting the outcome of CIP.

[Research progress on the regulatory mechanism of non-coding RNA in arsenic toxicity].

Arsenic is a non-metallic element, and the International Agency for Research on Cancer has identified arsenic and its compounds as carcinogens. Arsenic and its compounds can be absorbed through the respiratory tract, skin and digestive tract, distributed in the liver, kidney, lung and skin, and cause damage. Non-coding RNAs are closely related to arsenic-induced nervous system disorders, cell necrosis, reproductive toxicity, and carcinogenesis. In recent years, the network regulation of microRNAs (miRNAs) , long non-coding RNAs (lncRNAs) , and circular RNAs (circRNAs) among non-coding RNAs in various diseases induced by arsenic has become a new research field. This paper summarizes the existing scientific research results, and expounds the mechanism of miRNAs, lncRNAs and circRNAs in arsenic toxicity, and provides basic data and theoretical basis for the prevention and treatment of arsenic poisoning.

[Effects of Nd(2)O(3) exposure of rare earth particles on C57 BL/6J male mice sex hormone secretion and CYP11A1/PLZF/STRA8 protein expression].

Objective: To explore the effects of Nd(2)O(3) exposure to rare earth particles on the secretion of sex hormones, cytochrome P450 family member 11A1 (CYP11A1) , spermatogenesis markers promyelocytic leukemia zinc finger protein (PLZF) and retinoic acid stimulating gene 8 (STRA8) protein in C57 BL/6J male mice. Methods: In March 2021, Forty-eight male C57 BL/6J mice aged 6-8 weeks divided into control group and Nd(2)O(3) exposure low, medium and high dose groups (exposing doses of 62.5, 125.0, 250.0 mg/ml Nd(2)O(3)) , 12 per group. The mice in the Nd(2)O(3) groups were perfused with different doses of Nd(2)O(3) suspension by a one-time non-exposing tracheal instillation method, and the control group was perfused with an equal volume of normal saline, with a volume of 0.1 ml, to establish a mouse reproductive function injury model. After 28 days of exposure, the mice's body weight, testes and epididymis were weighed, and the organ coefficients were calculated; the two epididymis were taken to make a sperm suspension to determine the sperm count, survival rate, and deformity rate; inductively coupled plasma mass spectrometry (ICP-MS) method was used to detect the content of Nd in mouse testis tissue; HE staining was used to detect testicular tissue pathological changes and quantitative analysis; enzyme-linked immunosorbent assay (ELISA) method was used to detect serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) and testosterone (T) content; western blot was used to detect the protein levels of CYP11A1, PLZF and STRA8 in testicular tissues. Results: Compared with the control group, with the increase of the exposure dose, the Nd content in the testis of the mice showed an increasing trend, the sperm survival rate and LH showed a decreasing trend, and the sperm deformity rate showed an increasing trend (P<0.05) ; Pathological showed that the number of sperm in the seminiferous tubules of the testicular tissue in the Nd(2)O(3) medium and high dose groups was significantly reduced, and the germinal epithelial disintegration, intraepithelial vacuolization, and exfoliation of spermatogenic cells and supporting cells occurred; The height of germinal epithelium was significantly reduced, and the percentage of damaged seminiferous tubules showed an increasing trend (P<0.05) ; FSH and T levels in serum in the middle and high dose groups of Nd(2)O(3), and CYP11A1, PLZF and STRA8 proteins in testicular tissues showed a downward trend with increasing dose (P<0.05) . Conclusion: The rare earth particulate Nd(2)O(3) may interfere with the expression of CYP11A1, PLZF and STRA8 protein, thereby causing the disorder of sex hormone secretion in the body, the maintenance of spermatogonia and the obstruction of the process of meiosis, causing reproductive function damage.

[Intelligent prediction of HER2 status based on breast histopathology].

Objective: To study the association between histopathological features and HER2 overexpression/amplification in breast cancers using deep learning algorithms. Methods: A total of 345 HE-stained slides of breast cancer from 2012 to 2018 were collected at the China-Japan Friendship Hospital, Beijing, China. All samples had accurate diagnosis results of HER2 which were classified into one of the 4 HER2 expression levels (0, 1+, 2+, 3+). After digitalization, 204 slides were used for weakly supervised model training, and 141 used for model testing. In the training process, the regions of interest were extracted through cancer detected model and then input to the weakly supervised classification model to tune the model parameters. In the testing phase, we compared performance of the single- and double-threshold strategies to assess the role of the double-threshold strategy in clinical practice. Results: Under the single-threshold strategy, the deep learning model had a sensitivity of 81.6% and a specificity of 42.1%, with the AUC of 0.67 [95% confidence intervals (0.560,0.778)]. Using the double-threshold strategy, the model achieved a sensitivity of 96.3% and a specificity of 89.5%. Conclusions: Using HE-stained histopathological slides alone, the deep learning technology could predict the HER2 status using breast cancer slides, with a satisfactory accuracy. Based on the double-threshold strategy, a large number of samples could be screened with high sensitivity and specificity.

LINC00941 promotes proliferation and metastasis of pancreatic adenocarcinoma by competitively binding miR-873-3p and thus upregulates ATXN2.

OBJECTIVE: Globally, the incidence and mortality of pancreatic adenocarcinoma (PAAD) have constantly increased. Long non-coding RNAs (lncRNAs) are considered as vital regulators in human cancers. This study aims to elucidate the role of LINC00941 in regulating PAAD progression and the molecular mechanism. PATIENTS AND METHODS: Through database analyses, the expression pattern of LINC00941 in PAAD tissues and its prognostic value were uncovered. Its level in PAAD cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). After knockdown of LINC00941, proliferative and metastatic rates in BxPC-3 and PANC-1 cells were examined by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assay, respectively. The axis of LINC00941/miR-873-3p/ATXN2 was tested by Dual-Luciferase reporter assay and Pearson correlation test. RESULTS: LINC00941 was abnormally upregulated in PAAD tissues, and linked to the prognosis. Knockdown of LINC00941 inhibited proliferative, migratory and invasive abilities in BxPC-3 and PANC-1 cells. MiR-873-3p was the target gene binding LINC00941, which was downregulated in PAAD tissues. Overexpression of miR-873-3p inhibited proliferative, migratory and invasive abilities in BxPC-3 and PANC-1 cells, and the inhibited trends were abolished by co-overexpression of LINC00941. Furthermore, ATXN2 was confirmed to be the target gene binding miR-873-3p, which was upregulated in PAAD tissues. It was negatively correlated to miR-873-3p and positively correlated to LINC00941. CONCLUSIONS: LINC00941 is upregulated in PAAD tissues. It stimulates PAAD to proliferate and metastasize by competitively binding miR-873-3p and thus upregulates ATXN2.

[Progress on clinical trials of cancer drugs in China, 2020].

Objective: To explore the latest progress of oncology drug clinical trials in China under COVID-19, as well as to provide decision-making evidence for related stakeholders. Research progress of oncology drug trials and approved cancer drugs in China in 2020 were systematically summarized and compared with 2019. Methods: Information Disclosure Platform for Drug Clinical Studies and China Food and Drug Administration Query System for Domestic and Imported Drug were searched for registered clinical trials and approved oncology drugs, respectively. The trial scope, stage, drug type, effect and mechanism of domestic and global pharmaceutical enterprises were compared between 2019 and 2020. Results: A total of 722 cancer drug trials registered in China in 2020, with an annual growth rate of 52.3%, accounting for 28.3% of all registered trials. Among them, 603 (83.5%) trials were initiated by domestic pharmaceutical enterprises, and 105 (14.5%) were international multicenter trials, phase I trials accounted for 44.5%. For all those trials, there were 458 cancer drug varieties, with an annual growth rate of 36.7%, and 361 (85.8%) were developed by domestic enterprises. Most of the investigational products were therapeutic innovative drugs (77.1%), major in tumor treatment (92.8%). In terms of mechanism, targeted drugs were the most popular, accounting for 76.6%, and programmed cell death-1 (PD-1) and epithelial growth factor receptor (EGFR) were the most common targets. In addition, there were 19 anticancer drugs from 17 companies approved in China in 2019, with 10 drugs from domestic companies. Lung cancer and breast cancer are the most common indications for both registered trials and marketed drugs. No statistically significant differences were found between 2020 and 2019 in terms of the distribution of trial sponsor, scope and stage, as well as the distribution of drug type, effect and mechanism (P>0.05). Conclusions: During the Covid-19 epidemic period, clinical trials of oncology drugs in China progress smoothly and maintain a high growth rate. Series of innovative products obtained by domestic enterprises in 2020 is the main driving force of development of oncology drug clinical trials in China.

[Comparison of clinical efficacy of robotic, laparoscopic and open surgery in the treatment of severe rectal prolapse].

Objective: To analyze and compare the efficacy of robotic, laparoscopic and open dorsal mesh rectopexy in the treatment of severe rectal prolapse. Methods: A retrospective cohort study was performed. Patients who had a full-thickness rectum pulled out of the anus before surgery and the length was greater than 8 cm, and underwent transabdominal dorsal mesh rectopexy were enrolled in the study. Those who had urinary or sexual dysfunction before surgery, could not perform sexual function scores due to lack of a fixed sexual partner or sexual activity after surgery, underwent laparotomy again during the perioperative period, were transferred to laparotomy during robotic or laparoscopic surgery, or had no complete information, were excluded. A total of 61 patients with severe rectal prolapse in the First Affiliated Hospital of Zhengzhou University from 2014 to 2018 were enrolled and divided into robotic group (20 cases), laparoscopic group (20 cases) and open group (21 cases) according to the operative procedure based on patients' will. Perioperative parameters were compared among the 3 groups. The International Prostatic Symptoms Score Scale (IPSS, higher score indicates more severe urinary dysfunction), the International Index of Erectile Function questionnaire (IIEF-15, lower score indicates more severe male sexual dysfunction) and the Female Sexual Function Index (FSFI-19, lower score indicates more severe female sexual dysfunction) were used to evaluate and compare the urinary and sexual function before and after operation. Results: There were no significant differences in baseline data among the 3 groups (all P>0.05). In the robotic, laparoscopic and open groups respectively, the operative time was (176.3±13.8) minutes, (160.2±12.1) minutes and (134.2±12.1) minutes; intraoperative blood loss was (58.5±18.9) ml, (67.9±15.7) ml and (114.2±8.4) ml; the first time to ambulation was (19.9±6.8) hours, (24.0±8.9) hours and (37.7±11.4) hours; the first time to gas passage was (31.8±6.8) hours, (35.7±8.9) hours and (49.2±11.2) hours; the hospitalization time was (11.0±1.4) days, (11.4±1.4) days and (13.3±2.1) days; whose differences among 3 groups were all significant (all P<0.001). While no significant differences in morbidity of complication and recurrence among 3 groups were observed (all P>0.05). In the robotic, laparoscopic and open groups respectively, the preoperative IPSS score was (4.2±1.7), (4.4±1.3), and (4.7±1.8); the IPSS score at postoperative 3-month was (8.5±2.5), (9.9±1.7), and (12.2±3.1); IPSS score at postoperative 12-month was (4.3±1.6), (5.8±1.3), and (6.3±1.5), respectively. Compared to preoperative score, postoperative IPSS score increased obviously, then decreased gradually (P<0.001). Preoperative male IIEE score was (22.8±1.8), (22.1±2.1), and (22.6±1.5). In the robotic, laparoscopic and open groups respectively, male IIEE score at postoperative 6-month was (19.6±2.1), (17.1±2.1), and (15.0±2.1); male IIEE score at postoperative 12-month was (22.4±1.6), (19.9±1.5), (17.9±1.8), respectively. Preoperative female FSFI score was (26.4±3.4), (26.6±3.2), and (26.6±3.0); female FSFI score at postoperative 6-month was (21.5±3.3), (18.9±2.9), (17.0±2.6); female FSFI score at postoperative 12-month was (26.1±2.7), (22.7±3.2), and (21.2±2.3), respectively. Postoperative male IIEE score and female FSFI score decreased significantly and then increased gradually with time, whose differences were all significant (all P<0.05). Postoperative IPSS, IIEE, and FSFI scores in the robotic group were superior to those in the laparoscopic and open groups (all P<0.05). Conclusion: Robotic surgery is safe and effective in the treatment of severe rectal prolapse, and is more advantageous in preserving urinary function and sexual function.

Mechanism of miR-122-5p regulating the activation of PI3K-Akt-mTOR signaling pathway on the cell proliferation and apoptosis of osteosarcoma cells through targeting TP53 gene.

OBJECTIVE: To explore the regulatory mechanism of microRNA-122-5p (miR-122-5) targeting tumor protein p53 (TP53) gene to mediate PI3K-Akt-mTOR signaling pathway on the proliferation and apoptosis of osteosarcoma (OS) cells. PATIENTS AND METHODS: With the collection of osteosarcoma and normal adjacent tissues, the mRNA of miR-122-5p, TP53, PTEN, PI3K, Akt, mTOR, Bim, Bax, and Bcl-2 was detected by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), followed by the detection of the protein expression by Western blot. The target relationship between miR-122-5p and TP53 gene was verified. The third generation osteosarcoma cells were divided into Blank group, miR-122-5p mimic negative control (NC) group, miR-122-5p mimic group, miR-122-5p inhibitor NC group, miR-122-5p inhibitor group, rapamycin group and miR-122-5p inhibitor + rapamycin group. Furthermore, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to detect the proliferation ability, cell cycle distribution and apoptosis of each group after transfection. RESULTS: The expression level of miR-122-5p in osteosarcoma was lower than that in normal tissues (p < 0.05), TP53, PTEN, Bim and Bax expression levels were decreased (all p < 0.05), while the expression levels of PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR and Bcl-2 were highly upregulated (all p < 0.05). TP53 had the lowest expression in osteosarcoma cell line U-2OS (p < 0.05), which was selected for subsequent cell experiments. TP53 was the target gene of miR-122-5p. Compared with Blank group, miR-122-5p mimic group had increased expression of miR-122-5p (all p < 0.05); besides, there were significantly increased expression of TP53, PTEN, Bim, and Bax in miR-122-5p mimic group and rapamycin group, while remarkably decreased expression of PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, and Bcl-2 (all p < 0.05), accompanied by increased proportion of cells in G0/G1 phase, decreased cell proportion in S phase, increased cell apoptosis and inhibited cell proliferation (all p < 0.05). The opposite trends were found in miR-122-5p inhibitor group relative to miR-122-5p mimic group and rapamycin group (all p < 0.05). Meanwhile, no significant difference was found in miR-122-5p inhibitor+rapamycin group when compared with that in Blank group (all p > 0.05) except for significantly decreased miR-122-5p expression (p < 0.05). CONCLUSIONS: Upregulation of miR-122-5p may inhibit the proliferation and promote the apoptosis of osteosarcoma cells by inhibiting the activation of PI3K-Akt-mTOR signaling pathway, which may be related to the targeted up-regulation of TP53 expression.

LINC00052 inhibits tumor growth, invasion and metastasis by repressing STAT3 in cervical carcinoma.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LINC00052 inhibits tumor growth, invasion and metastasis by repressing STAT3 in cervical carcinoma, by J. Lin, L.-L. Nong, M.-Q. Li, F.-C. Yang, S.-H. Wang, M.-J. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (11): 4673-4679-DOI: 10.26355/eurrev_201906_18047-PMID: 31210293" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18047.

[Pathological diagnosis of lung cancer based on deep transfer learning].

Objective: To establish an artificial intelligence (AI)-assisted diagnostic system for lung cancer via deep transfer learning. Methods: The researchers collected 519 lung pathologic slides from 2016 to 2019, covering various lung tissues, including normal tissues, adenocarcinoma, squamous cell carcinoma and small cell carcinoma, from the Beijing Chest Hospital, the Capital Medical University. The slides were digitized by scanner, and 316 slides were used as training set and 203 as the internal test set. The researchers labeled all the training slides by pathologists and establish a semantic segmentation model based on DeepLab v3 with ResNet-50 to detect lung cancers at the pixel level. To perform transfer learning, the researchers utilized the gastric cancer detection model to initialize the deep neural network parameters. The lung cancer detection convolutional neural network was further trained by fine-tuning of the labeled data. The deep learning model was tested by 203 slides in the internal test set and 1 081 slides obtained from TCIA database, named as the external test set. Results: The model trained with transfer learning showed substantial accuracy advantage against the one trained from scratch for the internal test set [area under curve (AUC) 0.988 vs. 0.971, Kappa 0.852 vs. 0.832]. For the external test set, the transferred model achieved an AUC of 0.968 and Kappa of 0.828, indicating superior generalization ability. By studying the predictions made by the model, the researchers obtained deeper understandings of the deep learning model. Conclusions: The lung cancer histopathological diagnostic system achieves higher accuracy and superior generalization ability. With the development of histopathological AI, the transfer learning can effectively train diagnosis models and shorten the learning period, and improve the model performance.

[Pathological changes of fatal coronavirus disease 2019 (COVID-19) in the lungs: report of 10 cases by postmortem needle autopsy].

Objectives: To observe the pulmonary changes with coronavirus disease 2019 (COVID-19) in postmortem needle specimens, to detect the presence of 2019 novel coronavirus(2019-nCoV) in the lung tissues, and to analyze the clinicopathological characteristics. Methods: For 10 decedents with 2019-nCoV infection in Wuhan, bilateral lungs underwent ultrasound-guided percutaneous multi-point puncture autopsy, and pulmonary pathological changes were described in routine hematoxylin-eosin staining (HE) slides. Electron microscopy was also performed. The reverse transcription polymerase chain reaction (RT-PCR) was employed to detect 2019-nCoV nucleic acid in lung tissue, and the pathological characteristics were demonstrated in combination with clinical data analysis. Results: Of the 10 deaths associated with COVID-19, 7 were male and 3 were female. The average age was 70 (39-87) years. Medical record showed that 7 patients had underlying diseases. The average course of disease was 30 (16-36) days. Nine cases showed fibrinous and suppurative exudation in the alveolar cavity accompanied by the formation of hyaline membrane, and fibroblastic proliferation of alveolar septum. Type Ⅱ alveolar epithelial cells showed reactive hyperplasia and desquamation. Many macrophages accumulated in the alveolar cavity. Capillary hyaline thrombus and intravascular mixed thrombus were noted. In some cases, acute bronchiolitis with mucous membrane exfoliation, accumulation of bronchiolar secretions, and bronchiolar epithelial metaplasia occurred. In the cohort, a large number of bacteria (cocci) were detected in 1 case and a large number of fungi (yeast type) were detected in 1 case. Nine cases were positive for the nucleic acids of 2019-nCoV while one case remained negative by RT-PCR. Coronavirus particles were detected in the cytoplasm of type Ⅱ alveolar epithelium. Conclusions: The pulmonary pathological changes of fatal COVID-19 are diffuse alveolar damage (DAD), mainly in the acute exudative stage and the organic proliferative stage. There are fibrinous exudate aggregation in alveolar cavity with hyaline membrane formation, fibroblastic proliferation in alveolar septum, and alveolar epithelial cell injuries with reactive hyperplasia and desquamation of type Ⅱ alveolar epithelial cells. A large amount of neutrophils and monocytes infiltration is present in most cases and bacteria and fungi are detected in some cases, suggesting a serious bacterial or fungal infection secondary to the DAD.

[Progress on clinical trials of cancer drugs in China, 2019].

Objective: To deliver macro understanding of the latest research progress on clinical trials and approved products of cancer drugs in China in 2019. Methods: The number of clinical trials and related investigational products by domestic and foreign enterprises in 2019 were acquired in the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, while listed drugs were obtained in the China Food and Drug Administration Query System for Domestic and Imported Drug. Characteristics on stage, scope, indication of those trials, classification and mechanism of involved products, as well as listed anticancer drugs were summarized and depicted. Results: There were 474 cancer drug trials registered in China in 2019, accounting for 21.8% of the total, and 397 (83.8%) were initiated by domestic pharmaceutical enterprises. Overall, international multicenter trials accounted for 13.1%, and phase I trials accounted for 47.3%. Compared with global enterprises, the proportion of international multi-center trials initiated by domestic companies is lower (4.8% vs. 55.8%, P<0.001), and the proportion of phase I clinical trials and bioequivalence trials is higher (51.9% vs. 23.4%, 19.4% vs. 1.3%, P<0.001). An accumulative of 27 cancer types were involved for all the cancer drug trials, and lung cancer, solid tumor, and breast cancer were the most common cancer types, with 103, 95 and 49 trials, respectively. For the three cancer types unique to Chinese population, gastric, liver and esophageal cancer, the total number of initiated trials was 47. For all those trials, there were 335 cancer drug varieties, with 86.0% developed by domestic pharmaceutical enterprises, including 300 therapeutic drugs, 30 adjunctive drugs and 5 preventive drugs. In terms of mechanism, targeted drugs and immune drugs were the most popular, accounting for 74.6% and 20.3%, respectively. In addition, 17 anticancer drugs targeting on 11 cancer types were approved in China in 2019. Conclusions: Clinical trials on cancer drugs in China have ushered a booming era, with large number of innovative agents represented by targeted drugs and immune drugs under clinical development or putting into clinical practice. Those local enterprises are playing more and more critical roles. Strengthening clinical research and development on Chinese unique cancer types is the key direction of future work.

[A review of immune-related adverse events associated with immunotherapy].

Immune checkpoint inhibitors have been approved for clinical application in China. However, the increased immune-related adverse event (irAE) needs more attention. This review summarized the incidence, characteristic clinical manifestation and treatment of irAEs associated with programmed cell death protein-1(PD-1) and programmed cell death ligand-1(PD-L1) inhibitors. To have a deep insight into irAE, the potential mechanisms, the different incidences of cancer types, influencing factors and the direction of future research were also discussed here to provide guidance for clinical oncologist to identify and monitor irAE.

LncRNA ADPGK-AS1 regulated cell proliferation, invasion, migration and apoptosis via targeting miR-542-3p in osteosarcoma.

OBJECTIVE: The functions of lncRNAs have been verified to be important biomarkers and regulators for diagnosis and treatment of human diseases. In osteosarcoma (OS), emerging evidence determined that lncRNA was associated with cell progression. However, due to the high incidence and recurrence rate of osteosarcoma, it is important to find an effective treatment for osteosarcoma. PATIENTS AND METHODS: QRT-PCR was used to detect the expression of ADPGK-AS1 and miR-542-3p in tissues and cells. Western blot was applied to measure the protein expression of CDK4, Cyclin D1, Bcl-2, Bax, Cleaved caspase-3, MMP-2, and MMP-9. MTT assay and flow cytometry were used to measure cell proliferation and apoptosis. Cell invasion and migration were determined using the transwell assay. Moreover, luciferase reporter assay was used to ensure the relation between ADPGK-AS1 and miR-542-3p. RESULTS: LncRNA ADPGK-AS1 expression was induced while miR-542-3p expression was reduced in OS tissues and cells. Functional experiments showed that inhibition of ADPGK-AS1 could decrease cell proliferation, migration, and invasion, as well as promoted cell apoptosis in OS cells. Also, miR-542-3p has been verified to be a target miRNA of ADPGK-AS1 and miR-542-3p could reverse the effects of ADPGK-AS1 on cell proliferation, apoptosis, migration, and invasion in OS cells. CONCLUSIONS: ADPGK-AS1 affected cell proliferation, invasion, migration, and apoptosis via targeting miR-542-3p in OS, providing a theoretical basis and a new therapeutic target for the diagnosis and treatment of OS.

LINC00052 inhibits tumor growth, invasion and metastasis by repressing STAT3 in cervical carcinoma.

OBJECTIVE: The vital role of long noncoding RNAs (lncRNAs) in tumor progression has been identified in numerous studies. In this research, the biological function of lncRNA LINC00052 during the development of cervical cancer was mainly explored. PATIENTS AND METHODS: LINC00052 expression was detected by quantitative Real-time polymerase chain reaction (qRT-PCR) in cervical cancer tissue samples and cell lines. Moreover, the correlation between LINC00052 expression level and disease-free survival rate of cervical cancer patients was analyzed. In vitro functions of LINC00052 in cervical cancer cells were evaluated by proliferation assay, wound healing assay and transwell assay. In addition, qRT-PCR and Western blot were utilized to explore the underlying mechanism of LINC00052 in mediating the progression of cervical cancer. RESULTS: LINC00052 expression level was lower in cervical cancer samples than that in adjacent tissues, which was correlated with disease-free survival time. Moreover, cell proliferation, migration and invasion were inhibited through overexpression of LINC00052 in vitro. The mRNA and protein expression of signal transducers and activators of transcription 3 (STAT3) was downregulated after overexpressing LINC00052 in cervical cancer cells. The STAT3 expression level was negatively correlated with the expression of LINC00052 in cervical cancer tissues. CONCLUSIONS: LINC00052 could repress metastasis and invasion of cervical cancer cell via suppressing STAT3. LINC00052 might be a novel tumor suppressor in cervical cancer.

MicroRNA-221 regulates proliferation of bovine mammary gland epithelial cells by targeting the STAT5a and IRS1 genes.

MicroRNAs (miRNA) play an essential role in mammary gland development and lactation. Previous studies in cattle have shown that miR-221 is highly expressed in peak compared with early lactation. However, the functions of miR-221 in bovine mammary gland epithelial cells and the mechanisms by which this miRNA affects cell proliferation and milk synthesis remain unclear. We hypothesized that miR-221 targets and modulates the expression of specific genes in the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and phosphatidylinositol 3-kinase-proteinkinase B/mammalian target of rapamycin (PI3K-Akt/mTOR) signaling pathways, which have crucial roles in lactation in cattle. Following transfection of miR-221 into cultured bovine mammary gland epithelial cells, inhibition of cell proliferation and reduced viability of these cells were observed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis. To elucidate the molecular mechanisms of the effects of miR-221 on cell proliferation, we selected potential candidate genes that can be targeted by miR-221 using bioinformatics prediction tools. The dual luciferase assay revealed that STAT5a, STAT3, and IRS1 interact with miR-221 by its direct binding to the 3'-untranslated regions (UTR) of these genes. Subsequent analysis showed that transfection of a miR-221 mimic resulted in significantly decreased expression of STAT5a and IRS1 at both the RNA and protein levels using quantitative real-time PCR and Western blot analyses. Furthermore, expression levels of the downstream genes SOCS3, AKT3, and mTOR that are regulated by STAT5a and IRS1 in the JAK-STAT and PI3K-Akt/mTOR signaling pathways, were also altered after miR-221 transfection. This is the first study to reveal the mechanisms by which miR-221 inhibits mammary gland epithelial cell proliferation by targeting STAT5a and IRS1, key genes in the PI3K-Akt/mTOR and JAK-STAT signaling pathways.