[Efficacy of allogeneic hematopoietic stem cell transplantation based on a total body irradiation conditioning treatment regimen for adult acute lymphocytic leukemia].

Objective: To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis. Methods: The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group (n=53) and the busulfan plus cyclophosphamide (Bu/Cy) group (n=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. Results: The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group (P=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group (P=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively (P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively (P=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively (P=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% (P=0.565), 34.0% and 35.7% (P=0.859), 43.4% and 33.3% (P=0.318), and 20.8% and 50.0% (P=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group (P=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively (P=0.120). The 2-year LFS was 58.5% and 50.0%, respectively (P=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively (P=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation (HR=0.304, 95% CI 0.135-0.688, P=0.004), whereas the effect on NRM was not significant (HR=1.393, 95% CI 0.355-5.462, P=0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. Conclusion: allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.

[Progress in PD-1/PD-L1, PD-L2 signaling pathway and its role in host anti-tuberculosis immunity].

Programmed cell death 1 (PD-1) and its ligands, PD-L1 and PD-L2, expressed on a variety of immune cells, play multiple regulatory roles in the host immune response to Mycobacterium tuberculosis infection. In this study, we reviewed that the regulatory roles of PD-1/PD-L1, PD-L2 signaling in the host adaptive immune response, such as the innate response of macrophages, and the interaction between T cells and macrophages in response to MTB. In addition, during MTB infection, PD-1/PD-L1, PD-L2 signaling is also involved in the host inflammatory response, as well as the potential roles of PD-1/PD-L1, PD-L2 in the diagnosis and treatment of tuberculosis.

[Interpretation of the surgical treatment of pancreatic cancer of the 2024 edition of the NCCN guidelines].

Pancreatic cancer is a highly malignant tumor in the digestive system, and radical surgery is the only possible means to cure pancreatic cancer at present. In the past decade, pancreatic surgery has been developing rapidly, with various new technologies and concepts emerging, among which the use of minimally invasive techniques and the popularization of neoadjuvant therapy concepts are the most notable. At the same time, the surgical treatment of pancreatic cancer still has a long way to go, and many problems need to be solved urgently. This article introduces the surgical treatment of pancreatic cancer in the 2024 edition of the NCCN guidelines, focusing on minimally invasive and open surgical treatments, expanded lymph node dissection, combined vascular resection and reconstruction, surgical treatment of pancreatic neck cancer and neoadjuvant therapy, and briefly discussing the unresolved issues.

[Curative effect of percutaneous microwave ablation therapy on hepatocellular carcinoma survival: a 15-year real-world study].

Objective: To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma. Methods: 2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival. Results: A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P < 0.001, especially for liver cancer 3.1~5.0 cm (P < 0.001). Conclusion: Microwave ablation therapy is a safe and effective method for BCLC stage 0-B, with significantly enhanced technical efficacy and survival rate over time.

[Spatial distribution pattern of local tumor progression analysis after microwave ablation of hepatocellular carcinoma based on three-dimensional magnetic resonance imaging].

Objective: To investigate the spatial distribution pattern of local tumor progression (LTP) for hepatocellular carcinoma (HCC) ≤5 cm after microwave ablation. Methods: A retrospective analysis was performed on 169 HCCs with matched MRI before and after ablation from December 2009 to December 2019. A tumor MRI was reconstructed using three-dimensional visualization technology. LTP was classified as contact or non-contact, early or late stage, according to whether LTP was in contact with the edge of the ablation zone and the occurrence time (24 months). The tumor-surrounded area was divided into eight quadrants by using the eight-quadrant map method. An analysis was conducted on the spatial correlation between the quadrant where the ablative margin (AM) safety boundary was located and the quadrant where different types of LTP occurred. The t-test, or rank-sum test, was used for the measurement data. 2-test for count data was used to compare the difference between the two groups. Results: The AM quadrant had a distribution of 54.4% LTP, 64.2% early LTP stage, and 69.1% contact LTP, suggesting this quadrant was much more concentrated than the other quadrants (P < 0.001). Additionally, the AM quadrant had only 15.2% of non-contact type LTP and 17.1% of late LTP, which was not significantly different from the average distribution probability of 12.5% (100/8%) among the eight quadrants (P = 0.667, 0.743). 46.6% of early contact type LTP was located at the ablation needle tip, 25.2% at the body, and 28.1% at the caudal, while the location distribution probabilities of non-early contact LTP were 34.8%, 31.8%, and 33.3%, respectively. Conclusion: LTP mostly occurs in areas where the ablation safety boundary is the shortest. However, non-contact LTP and late LTP stages exhibit the feature of uniform distribution. Thus, this type of LPT may result from an inadequate non-ablation safety boundary.

[Clinical effects of flaps or myocutaneous flaps transplantation after titanium mesh-retaining debridement in repairing the wounds with exposed titanium mesh after cranioplasty].

Objective: To explore the clinical effects of flaps or myocutaneous flaps transplantation after debridement to repair the wounds with exposed titanium mesh after cranioplasty on the premise of retaining the titanium mesh. Methods: This study was a retrospective observational study. From February 2017 to October 2022, 22 patients with titanium mesh exposure after cranioplasty who met the inclusion criteria were admitted to the Department of Plastic, Aesthetic & Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University, including 15 males and 7 females, aged from 19 to 68 years. After admission, treatments such as bacterial culture of wound exudate sample, anti-infection, and dressing change were carried out. Thorough surgical debridement was performed when the wound improved, and the wound area was 3.0 cm×2.0 cm to 11.0 cm×8.0 cm after debridement. The wound was repaired with local flaps, expanded flaps, or free latissimus dorsi myocutaneous flaps according to the size, location, severity of infection, and surrounding tissue condition of the wounds, and the areas of flaps or myocutaneous flaps were 5.5 cm×4.0 cm to 18.0 cm×15.0 cm. The donor areas of flaps were sutured directly or repaired by split-thickness skin grafts from head. The wound repair method was recorded. The survivals of flaps or myocutaneous flaps after surgery and wound healing in 2 weeks after surgery were recorded. During postoperative follow-up, recurrence of infection or titanium mesh exposure in the implanted area of titanium mesh was observed; the head shapes of patients, scar formation of the operative incision, and baldness were observed. At the last follow-up, the satisfaction of patients with the treatment effect (dividing into three levels: satisfied, basically satisfied, and dissatisfied) was evaluated. The total treatment costs of patients during their hospitalization were calculated. Results: The wounds in 11 cases were repaired with local flaps, the wounds in 5 cases were repaired with expanded flaps, and the wounds in 6 cases were repaired with free latissimus dorsi myocutaneous flaps. All flaps or myocutaneous flaps survived completely after surgery, and all wounds healed well in 2 weeks after surgery. Follow up for 6 to 48 months after operation, only one patient with local flap grafting experienced a recurrence of infection in the titanium mesh implanted area at more than one month after surgery, and the titanium mesh was removed because of ineffective treatment. Except for one patient who had a local depression in the head after removing the titanium mesh, the rest of the patients had a full head shape. Except for myocutaneous flap grafting areas in 6 cases and skin grafting area in 1 case with local flaps grafting had no hair growth, the other patients had no baldness. All the scars in surgical incision were concealed. At the last follow-up, 19 cases were satisfied with the treatment effects, 2 cases were basically satisfied, and 1 case was dissatisfied. The total treatment cost for patients in this group during hospitalization was 11 764-36 452 (22 304±6 955) yuan. Conclusions: For patients with titanium mesh exposure after cranioplasty, on the premise of adequate preoperative preparation and thorough debridement, the wound can be repaired with appropriate flaps or myocutaneous flaps according to the wound condition. The surgery can preserve all or part of the titanium mesh. The postoperative wound healing is good and the recurrence of infection or titanium mesh exposure in the titanium mesh implanted area is reduced, leading to good head shape, reduced surgical frequency, and decreased treatment costs.

The Clinical Significance of Subtle Distal Fallopian Tube Abnormalities: A Multicentre Prospective Observational Study.

Background: Subtle distal fallopian tube abnormalities are a group of diseases characterised by small variations in tubal anatomy. The clinical significance of these abnormalities need to be studied. Objectives: The purpose of this multicentre prospective observational study was to investigate whether subtle distal fallopian tube abnormalities are related to infertility and endometriosis. Materials and Methods: The investigation was carried out in five medical centres in China and France from February to July 2021 and included reproductive-age patients who underwent gynaecological laparoscopy. Subtle abnormalities included Hydatid of Morgagni (HM) , fimbrial agglutination, tubal diverticula, accessory ostium, fimbrial phimosis, and accessory fallopian tube. Results: 642 patients were enrolled in the study and 257 (40.0%) were diagnosed with subtle tube abnormalities. Hydatid of Morgagni was the most common abnormality (22.7%; n=146), followed by fimbrial agglutination (19.8%; n=127), tubal diverticula (6.9%; n=44), accessory tube (2.0%; n=13), and tubal accessory ostium (1.9%; n=12). Fimbrial phimosis was the least common abnormality (0.3%; n=2). The prevalence of subtle fallopian tube abnormalities was significantly higher among infertile patients (188/375, 50.1%) than those without history of infertility (69/267, 25.8%, ᶍ2=38.332, P=0.000). 209 patients were diagnosed with endometriosis during surgery, and the prevalence of subtle abnormalities was significantly higher in the endometriosis group than in those without endometriosis (61.2%, [128/209] vs. 29.8% [129/433], ᶍ2=58.086, P=0.000). Conclusions: Higher prevalence of subtle tubal abnormalities suggests that they may contribute to infertility. They are highly related to endometriosis and indicate fimbrial abnormalities of endometriosis. What is new?: This is the largest multicentre study to investigate the subtle distal fallopian tube abnormalities in infertile women. Compared to previous studies, this study includes the main subtle distal abnormalities and the control group patients without a history of infertility.

[Research progress on HEG1 in cardiovascular generation and tumor development].

Heart development protein with EGF-like domains 1 (HEG1) is a novel mucin-like membrane protein with a long O-glycosylation region and EGF domain. HEG1 plays critical roles in embryo development and cardiogenesis, and is closely related to the occurrence and progression of malignant tumors. Here this article demonstrates the research progress on HEG1 in cardiovascular formation and tumor development in recent years, to inspire new ideas for the pathogenesis, diagnosis and treatment of related diseases.

[Clinical analysis of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma].

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.

[A case of lung adenocarcinoma with markedly elevated amylase in airway secretions].

A 45-year-old male patient was admitted to the hospital because of intermittent cough and expectoration for more than 1 year, worsened by dyspnea for 2 months, and was finally diagnosed with lung adenocarcinoma. The CT scan of the chest revealed lesions of diversity with fibrosis, mass and effusion, but his severe cough limited biopsy of the lesions. The difficult process of diagnosis was aided by the further analysis of the sputum, which showed significantly elevated amylase without any evidence of pancreatic disease. The cough was relieved by intravenous pumping octreotide acetate, and both CT-guided lung biopsy and transbronchial biopsy revealed the lung adenocarcinoma. The diagnostic process of this case provided a helpful diagnostic thinking and demonstrated the rare clinical features of lung adenocarcinoma.

Nivolumab plus chemotherapy in first-line metastatic non-small-cell lung cancer: results of the phase III CheckMate 227 Part 2 trial.

BACKGROUND: In CheckMate 227 Part 1, first-line nivolumab plus ipilimumab prolonged overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% versus chemotherapy. We report results from CheckMate 227 Part 2, which evaluated nivolumab plus chemotherapy versus chemotherapy in patients with metastatic NSCLC regardless of tumor PD-L1 expression. PATIENTS AND METHODS: Seven hundred and fifty-five patients with systemic therapy-naive, stage IV/recurrent NSCLC without EGFR mutations or ALK alterations were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus chemotherapy or chemotherapy. Primary endpoint was OS with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC. OS in all randomized patients was a hierarchically tested secondary endpoint. RESULTS: At 19.5 months' minimum follow-up, no significant improvement in OS was seen with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC [median OS 18.8 versus 15.6 months, hazard ratio (HR) 0.86, 95.62% confidence interval (CI) 0.69-1.08, P = 0.1859]. Descriptive analyses showed OS improvement with nivolumab plus chemotherapy versus chemotherapy in all randomized patients (median OS 18.3 versus 14.7 months, HR 0.81, 95.62% CI 0.67-0.97) and in an exploratory analysis in squamous NSCLC (median OS 18.3 versus 12.0 months, HR 0.69, 95% CI 0.50-0.97). A trend toward improved OS was seen with nivolumab plus chemotherapy versus chemotherapy, regardless of the tumor mutation status of STK11 or TP53, regardless of tumor mutational burden, and in patients with intermediate/poor Lung Immune Prognostic Index scores. Safety with nivolumab plus chemotherapy was consistent with previous reports of first-line settings. CONCLUSIONS: CheckMate 227 Part 2 did not meet the primary endpoint of OS with nivolumab plus chemotherapy versus chemotherapy in patients with metastatic nonsquamous NSCLC. Descriptive analyses showed prolonged OS with nivolumab plus chemotherapy in all-randomized and squamous NSCLC populations, suggesting that this combination may benefit patients with untreated metastatic NSCLC.

Lateral Intraventricular Epidermoid Cyst: A Case Report and Literature Review.

Epidermoid cysts originate from ectopic embryonic epithelial cells and are a very common type of benign intracranial tumor. However, the incidence of intraventricular epidermoid cysts is low, and lateral intraventricular epidermoid cysts are even rarer. Here, we present a case of lateral intraventricular epidermoid cyst and review the relevant literature. A 54-year-old female complained of recurrent headaches over a 5-year period, with aggravated symptoms during the last 2 months or more. A computed tomography of the brain showed a low-density mass in the lateral ventricle and enlargement of the right ventricle. Cranial magnetic resonance imaging further confirmed that the mass was an epidermoid cyst. The patient underwent microscopic surgical resection combined with endoscopy using an interhemispheric craniotomy approach. The mass was satisfactorily removed, and the patient recovered well. Lateral intraventricular epidermoid cysts often present with clinical symptoms due to the invasion of surrounding brain tissue or blockage of the cerebrospinal fluid system. Diagnosis relies on examination by magnetic resonance imaging, and treatment relies on surgical resection. The prognoses of patients are mostly excellent and depend on whether the tumor is resected cleanly or not.

[Changes of brain network in patients with insomnia following radiotherapy for cervical cancer and their correlation with IT-TMS treatment efficacy: a graph-theory analysis].

OBJECTIVE: To analyze the changes of brain small-world and node function network properties in patients with insomnia following radiotherapy for cervical cancer based on graph theory analysis and explore the correlation between functional networks and the clinical efficacy of individual-target transcranial magnetic stimulation (IT-TMS) for treatment of insomnia. METHODS: The resting state functional magnetic resonance imaging (rs-fMRI) data were collected from 30 patients with insomnia following radiotherapy for cervical cancer and 30 matched healthy individuals. All the patients received accelerated intelligent neuromodulation TMS therapy. Using graph theory analysis and GRETNA software, the functional connectivity matrices were constructed and the attribute features were extracted. The scores on the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) of the participants were collected before and after IT-TMS, and the correlation between improvement in insomnia and the functional network was investigated. RESULTS: The two groups matched for age, gender, and education level (P>0.05) showed significant differences in PSQI, ISI, SAS and SDS scores (P<0.05). Both groups showed attributes of the small-world network. Compared with the healthy individuals, the patients showed significantly decreased σ, EI, Cp and Lp (P<0.05) and increased Eg (P<0.05) at baseline, which, along with insomnia symptoms, were all improved after IT-TMS treatment. The patients showed reduced functional connections of the node network at follow-up compared with the baseline, and the low functional connectivity between the right insula and left superior frontal gyrus was correlated with the improvement of ISI scores. CONCLUSION: The patients with insomnia following radiotherapy for cervical cancer have impaired information integration ability of the brain network, IT-TMS can significantly improve insomnia symptoms by reducing the hyperconnectivity between the default mode network and the salience network.

Unintended placement of a double-J stent in the contralateral renal pelvis during laparoscopic pyeloplasty for pediatric hydronephrosis: a case report.

BACKGROUND: The double-J stent (DJS) is a commonly used ureteral stent in urological surgeries, which provides support and drainage. However, the DJS may result in various complications such as infection, hematuria, stone formation, stent occlusion, and migration. Normally, one end of the DJS is located in the renal pelvis, and the other end in the bladder. In this case report, we describe the rare occurrence of a misplaced DJS during laparoscopic pyeloplasty, which was unintentionally placed in the contralateral renal pelvis. CASE REPORT: A 4-month-old male infant was diagnosed with left hydronephrosis. After confirmation of the diagnosis, laparoscopic left pyeloplasty was performed with the placement of a DJS. The patient did not experience any discomfort, such as nausea, vomiting, refusal to feed, crying and restlessness, or fever, after the operation, and was discharged on postoperative day 4. The patient returned to the hospital for DJS removal 6 weeks after the operation. However, the kidneys, ureters, and bladder (KUB) X-ray examination showed that the DJS was unintentionally placed in the contralateral ureter and renal pelvis. The stent was confirmed and removed under cystoscopy. Postoperative examination of the DJS showed that there was a hole in the side of the middle of the stent for urine drainage, with no obstruction or contralateral hydronephrosis. CONCLUSIONS: Misplacement of a DJS in the contralateral renal pelvis during laparoscopic pyeloplasty is a rare but potentially serious complication. Surgeons should be cautious when placing the stent and confirm its placement with imaging studies. Patients should be closely monitored for postoperative complications and prompt intervention should be taken if necessary.

CLDN6 Suppresses Migration and Invasion of MCF-7 and SKBR-3 Breast Cancer Cells by Blocking the SMAD/Snail/MMP-2/9 Axis.

The study examined the mechanisms of action of signal protein claudin 6 (CLDN6) on migration and invasion of breast cancer cell lines MCF-7 and SKBR-3. To this end, the signal proteins SMAD were blocked with their inhibitor SB431542, the genes CLDN6 and SNAIL were knocked down with short hairpin RNAs, and MMP2 and MMP9 were inhibited with TIMP-1. Expressions of MMP2 and MMP9 mRNAs were evaluated by reverse transcription PCR, Expressions of MMP-2, MMP-9, E-cadherin, N-cadherin, and vimentin were examined by Western blotting. Migration and invasion were analyzed by scratch test and Matrigel invasion assay. SB431542 inhibited expression of MMP2 and MMP9 in both cell lines. Single use of SB431542 inhibited expression of MMP-2/MMP-9 and corresponding mRNAs, but subsequent silencing of CLDN6 gene reversed this effect. TIMP-1 reversed down-regulation of E-cadherin, upregulation of N-cadherin and vimentin, facilitation of migration and invasion evoked by CLDN6 knocking down. Silencing of SNAIL gene inhibited migration and invasion, upregulated the expression of E-cadherin, and down-regulated expression of MMP2, MMP 9, N-cadherin, and vimentin. Thus, CLDN6 suppresses the epithelial-mesenchymal transition, migration, and invasion via blocking SMAD/Snail/MMP-2/9 signaling pathway in MCF-7 and SKBR-3 cancer cell lines.

[Efficacy and safety of superpulse thulium laser lithotripsy in the intracavitary treatment of urinary calculi].

Objective: To evaluate the efficacy and safety of superpulse thulium laser lithotripsy in the intracavitary treatment of urinary calculi. Methods: From May 2021 to July 2022, patients diagnosed with urinary calculi were screened in four medical centers. Those who met the criteria were treated with superpulse thulium fiber laser under endoscope. The patients' perioperative conditions were recorded. The main effective index was stone-free rate (SFR) 4 weeks after operation, the main safety index was the failure rate of the experimental instruments during operation, and the secondary safety index was the incidence rate of perioperative complications. Results: A total of 76 eligible patients completed superpulse thulium fiber laser lithotripsy, with an average age of (52.0±11.1) years, 54 males and 22 females. There were 31 renal stones, 43 ureteral stones and 2 bladder stones. Percutaneous nephrolithotomy was performed in 17 patients. Ureteroscopy lithotripsy/flexible ureteroscopy lithotripsy was performed in 57 patients and transurethral bladder lithotripsy was in 2 patients. The lithotripsy time of all patients was (50.9±31.4) minutes. There was no failure of experimental instruments during the operation. Six patients refused follow-up examination after operation. The incidence of postoperative adverse events was 61.8% (47/76). One patient needed hospitalization due to inguinal hernia after operation, and the rest were classified as Clavien-dindo grade 1-2. The SFR was 94.3% (66/70) at 4 weeks after operation. Conclusion: It is effective and safe to use superpulse thulium fiber laser in the treatment of urinary calculi.

Triple-negative breast cancer: predictive model of early recurrence based on MRI features.

AIM: To develop an integrated model based on preoperative magnetic resonance imaging (MRI) features for predicting early recurrence in patients with triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Women with TNBC who underwent breast MRI and surgery between 2009 and 2019 were evaluated retrospectively. Two breast radiologists reviewed MRI images independently based on the Breast Imaging Reporting and Data System Lexicon (BI-RADS), and classified the breast oedema scores on T2-weighted imaging (WI) as no oedema, peritumoural oedema, prepectoral oedema, or subcutaneous oedema. The relationship between disease-free survival (DFS) and MRI features was analysed by Cox regression, and a nomogram model was generated based on the results. RESULTS: 150 patients with TNBC were included and divided into a training cohort (n=78) and validation cohort (n=72). MRI features including subcutaneous oedema and rim enhancement showed a tendency to worsen DFS in univariate analysis. Multivariate analysis showed that subcutaneous oedema (p=0.049, HR [95% confidence interval {CI} = 8.24 [1.01-67.52]) and rim enhancement (p=0.016, HR [95% CI] = 4.38 [1.32-14.54]) were independent predictors for DFS. In the nomogram, the areas under the curves (AUCs) of the training cohort was 0.808, and that of the validation cohort was 0.875. CONCLUSION: The presence of subcutaneous oedema or rim enhancement on preoperative breast MRI was shown to be a good predictor of poor survival outcomes in patients with TNBC.