Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial.

BACKGROUND: Triple-negative breast cancers display heterogeneity in molecular drivers and immune traits. We previously classified triple-negative breast cancers into four subtypes: luminal androgen receptor (LAR), immunomodulatory, basal-like immune-suppressed (BLIS), and mesenchymal-like (MES). Here, we aimed to evaluate the efficacy and safety of subtyping-based therapy in the first-line treatment of triple-negative breast cancer. METHODS: FUTURE-SUPER is an ongoing, open-label, randomised, controlled phase 2 trial being conducted at Fudan University Shanghai Cancer Center (FUSCC), Shanghai, China. Eligible participants were females aged 18-70 years, with an Eastern Cooperative Oncology Group performance status of 0-1, and histologically confirmed, untreated metastatic or recurrent triple-negative breast cancer. After categorising participants into five cohorts according to molecular subtype and genomic biomarkers, participants were randomly assigned (1:1) with a block size of 4, stratified by subtype, to receive, in 28-day cycles, nab-paclitaxel (100 mg/m2, intravenously on days 1, 8, and 15) alone (control group) or with a subtyping-based regimen (subtyping-based group): pyrotinib (400 mg orally daily) for the LAR-HER2mut subtype, everolimus (10 mg orally daily) for the LAR-PI3K/AKTmut and MES-PI3K/AKTmut subtypes, camrelizumab (200 mg intravenously on days 1 and 15) and famitinib (20 mg orally daily) for the immunomodulatory subtype, and bevacizumab (10 mg/kg intravenously on days 1 and 15) for the BLIS/MES-PI3K/AKTWT subtype. The primary endpoint was investigator-assessed progression-free survival for the pooled subtyping-based group versus the control group in the intention-to-treat population (all randomly assigned participants). Safety was analysed in all patients with safety records who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT04395989). FINDINGS: Between July 28, 2020, and Oct 16, 2022, 139 female participants were enrolled and randomly assigned to the subtyping-based group (n=69) or control group (n=70). At the data cutoff (May 31, 2023), the median follow-up was 22·5 months (IQR 15·2-29·0). Median progression-free survival was significantly longer in the pooled subtyping-based group (11·3 months [95% CI 8·6-15·2]) than in the control group (5·8 months [4·0-6·7]; hazard ratio 0·44 [95% CI 0·30-0·65]; p<0·0001). The most common grade 3-4 treatment-related adverse events were neutropenia (21 [30%] of 69 in the pooled subtyping-based group vs 16 [23%] of 70 in the control group), anaemia (five [7%] vs none), and increased alanine aminotransferase (four [6%] vs one [1%]). Treatment-related serious adverse events were reported for seven (10%) of 69 patients in the subtyping-based group and none in the control group. No treatment-related deaths were reported in either group. INTERPRETATION: These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway. FUNDING: National Natural Science Foundation of China, Natural Science Foundation of Shanghai, Shanghai Hospital Development Center, and Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Subtyping-based platform guides precision medicine for heavily pretreated metastatic triple-negative breast cancer: The FUTURE phase II umbrella clinical trial.

Triple-negative breast cancer (TNBC) is a heterogeneous disease and lacks effective treatment. Our previous study classified TNBCs into four subtypes with putative therapeutic targets. Here, we report the final results of FUTURE, a phase II umbrella trial designed to explore whether the subtyping-based strategy may improve the outcomes in metastatic TNBC patients. A total of 141 patients with a median of three previous lines of therapies in the metastatic setting were enrolled in seven parallel arms. Confirmed objective responses were achieved in 42 patients (29.8%; 95% confidence interval [CI], 22.4-38.1). The median values of progression-free survival and overall survival were 3.4 (95% CI: 2.7-4.2) and 10.7 (95% CI: 9.1-12.3) months, respectively. Given Bayesian predictive probability, efficacy boundaries were achieved in four arms. Furthermore, integrated genomic and clinicopathological profiling illustrated associations of clinical and genomic parameters with treatment efficacy, and the efficacy of novel antibody-drug conjugates was explored in preclinical TNBC models of subtypes for which treatment was futile. In general, the FUTURE strategy recruits patients efficiently and provides promising efficacy with manageable toxicities, outlining a direction for further clinical exploration.

Rheology of saliva in health and disease.

BACKGROUND: Saliva is a complex fluid that lubricates the oropharynx and facilitates chewing, swallowing, and vocalization. Viscoelasticity is critical for the ability of saliva to fulfill these functions. Xerostomia, or a sensation of dry mouth, occurs in 17-26% of the population. Although many equate xerostomia with hyposalivation, high-risk patients frequently report oral dryness in the absence of decreased salivary flow. OBJECTIVE: This study aims to determine if xerostomia is associated with alterations in the rheological properties of saliva in addition to decreased salivary production. METHODS: The study population included patients with post-radiation xerostomia, patients with anticholinergic-induced xerostomia and healthy controls. Salivary volumetric flow rate was measured, shear viscosity was measured using oscillatory rheometry, and extensional viscosity was measured using capillary thinning methods. Groups were compared using descriptive statistics and univariate analysis. RESULTS: A total of 36 subjects were included: 15 with post-radiation xerostomia, 9 with anticholinergic-induced xerostomia and 12 controls. Salivary volumetric flow was significantly decreased in post-radiation and anticholinergic-induced patients compared to controls. On capillary thinning testing, saliva from xerostomia patients had significantly greater extensional viscosity compared to controls. However, saliva from the three groups showed no significant difference in the complex viscosity or the storage or loss modulus of saliva with oscillatory rheology. CONCLUSIONS: Xerostomia is associated with decreased salivary volumetric flow and quantitative changes in the rheologic properties of saliva.

Omission of axillary surgery for ipsilateral breast tumor recurrence with negative nodes after previous breast-conserving surgery: is it oncologically safe?

PURPOSE: Salvage mastectomy is traditionally recommended for patients who developed ipsilateral breast tumor recurrence (IBTR) in light of previous breast irradiation. However, it remains controversial whether surgical axillary staging (SAS) is necessary for IBTR patients with negative nodes. This study aimed to evaluate the oncologic safety of omitting SAS for IBTR. METHODS: We retrospectively identified patients who developed invasive IBTR with negative nodes after undergoing breast-conserving surgery (BCS) from 2010 to 2018. Patterns of care in nodal staging were analyzed based on prior axillary staging status. Clinicopathologic characteristics and adjuvant treatment of the initial tumor, as well as the IBTR, were compared between the SAS and no SAS groups. Kaplan-Meier method and Cox regression model were utilized to compare the locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates after IBTR removal between the two groups. RESULTS: A total of 154 IBTR patients were eligible for final analysis. Compared to the no SAS group, SAS group was less likely to undergo ALND (15.1 vs 73.3%, p < 0.001) at initial BCS, had a longer recurrence interval (2.8 vs 2.1 years, p = 0.03), and were more likely to have discordant molecular subtype (35.8 vs 12.9%, p = 0.001) and different quadrant location (37.7 vs 19.8%, p = 0.02) with primary tumor. However, the extent of axillary staging did not affect systemic or radiation recommendations. In the subgroup of patients without previous ALND, the clinicopathologic characteristics were roughly comparable. No significant differences were observed in LRRFS, DMFS or OS between the two groups. CONCLUSION: For node-negative IBTR patients, we observed selection bias on the basis of prior ALND, shorter recurrence interval, and concordant molecular subtype favoring no SAS but comparable LRRFS, DMFS, and OS. These results support a wider consideration of sparing SAS in the management of IBTR, especially in patients without previous ALND.

A nanodevice with lifetime-improved singlet oxygen for enhanced photodynamic therapy.

The short lifetime of singlet oxygen reduces its accumulation in the endoplasmic reticulum, which limits the output of photodynamic therapy. A nanodevice with functions of singlet oxygen production, storage and release can improve the lifetime of singlet oxygen for enhancing phototherapeutic efficacy.

Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial.

PURPOSE: Camrelizumab, an mAb against programmed cell death protein 1 (PD-1), plus nab-paclitaxel exhibited promising antitumor activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC). Famitinib is a tyrosine kinase inhibitor targeting VEGFR2, PDGFR, and c-kit. We aimed to assess the efficacy and safety of a novel combination of famitinib, camrelizumab, and nab-paclitaxel in advanced immunomodulatory TNBC. PATIENTS AND METHODS: This open-label, single-arm, phase II study enrolled patients with previously untreated, advanced, immunomodulatory TNBC (CD8 IHC staining ≥10%). Eligible patients received 20 mg of oral famitinib on days 1 to 28, 200 mg of i.v. camrelizumab on days 1 and 15, and i.v. nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 in 4-week cycles. The primary endpoint was objective response rate (ORR), as assessed by investigators per RECIST v1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and exploratory biomarkers. RESULTS: Forty-eight patients were enrolled and treated. Median follow-up was 17.0 months (range, 8.7-24.3). Confirmed ORR was 81.3% [95% confidence interval (CI), 70.2-92.3], with five complete and 34 partial responses. Median PFS was 13.6 months (95% CI, 8.4-18.8), and median DOR was 14.9 months [95% CI, not estimable (NE)-NE]. Median OS was not reached. No treatment-related deaths were reported. Among 30 patients with IHC, 13 (43.3%) were programmed death-ligand 1 (PD-L1)-negative, and PD-L1 was associated with favorable response. PKD1 and KAT6A somatic mutations were associated with therapy response. CONCLUSIONS: The triplet regimen was efficacious and well tolerated in previously untreated, advanced, immunomodulatory TNBC. The randomized controlled FUTURE-SUPER trial is under way to validate our findings. See related commentary by Salgado and Loi, p. 2728.

A novel approach to myringotomy simulation.

OBJECTIVE: In the wake of the 2019 coronavirus disease pandemic, elective cases and opportunities for clinical application have decreased, and the need for useful simulation models has become more apparent for developing surgical skills. A novel myringotomy with ventilatory tube insertion simulation model was created. METHODS: Residents across all levels at our institution participated in the simulation. Participants were evaluated in terms of: time of procedure, microscope positioning, cerumen removal, identification of middle ear effusion type, canal wall trauma, tympanic membrane damage and tube placement. RESULTS: Eleven residents participated. Scores ranged from 14 to 34, out of a maximum of 40. The average score among junior and senior residents was 24 and 31, respectively. The simulation was felt to be representative of the operating theatre experience. CONCLUSION: This study demonstrates a low-cost simulation model that captures several important, nuanced aspects of myringotomy with tube insertion, often overlooked in previously reported simulations.

Breast-conserving in centrally located breast cancer patients confirmed safe by SEER based study.

BACKGROUND: Due to the lack of high-level data, there is still controversy over the oncological safety of breast conservation in patients with centrally located breast cancer. This study aimed to assess the safety of breast-conserving surgery in patients with centrally located breast cancer based on the data from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: We collected data for all cases diagnosed with breast cancer who underwent breast-conserving surgery from 2012-2014 in the SEER database. The primary outcome of our study was disease-specific survival (DSS) and overall survival (OS). The PSM was used to eliminate the effects of non-random statistics. Chi-square test, Kaplan-Meier method and Cox proportional hazards regression model on univariate and multivariate analysis were used to analyze the data. RESULTS: Data from 79,214 patients who had undergone breast-conserving surgery were analyzed in this study, including those with breast cancer in the central region (n=3,128) and outside the central region (n=76,086). The DSS of central breast cancer patients and outside the central breast cancer patients was 58.1 months versus 58.0 months (P>0.05), respectively, while the OS of the 2 groups was 58.0 months versus 58.0 months (P>0.05), respectively. CONCLUSIONS: Breast cancer in the central region should not be contraindicated for breast conserving surgery and breast-conserving surgery can benefit a wider range of patients.

Biosynthetic gene cluster profiling predicts the positive association between antagonism and phylogeny in Bacillus.

Understanding the driving forces and intrinsic mechanisms of microbial competition is a fundamental question in microbial ecology. Despite the well-established negative correlation between exploitation competition and phylogenetic distance, the process of interference competition that is exemplified by antagonism remains controversial. Here, we studied the genus Bacillus, a commonly recognized producer of multifarious antibiotics, to explore the role of phylogenetic patterns of biosynthetic gene clusters (BGCs) in mediating the relationship between antagonism and phylogeny. Comparative genomic analysis revealed a positive association between BGC distance and phylogenetic distance. Antagonistic tests demonstrated that the inhibition phenotype positively correlated with both phylogenetic and predicted BGC distance, especially for antagonistic strains possessing abundant BGCs. Mutant-based verification showed that the antagonism was dependent on the BGCs that specifically harbored by the antagonistic strain. These findings highlight that BGC-phylogeny coherence regulates the positive correlation between congeneric antagonism and phylogenetic distance, which deepens our understanding of the driving force and intrinsic mechanism of microbial interactions.

Spatiotemporal Patterns of Loco-Regional Recurrence After Breast-Conserving Surgery.

BACKGROUND: Loco-regional recurrences (LRR) following breast-conserving surgery (BCS) remain a heterogeneous class of disease that has significant variation in its biological behavior and prognosis. METHODS: To delineate the spatiotemporal patterns of LRR after BCS, we analyzed the data of 4325 patients treated with BCS from 2006 to 2016. Clinico-pathological and treatment specific factors were analyzed using the Cox proportional hazards model to identify factors predictive for LRR events. Recurrence patterns were scrutinized based on recurrence type and recurrence-free interval (RFI). Annual recurrence rates (ARR) were compared according to recurrence type and molecular subtype. RESULTS: With a median follow-up of 66 months, 120 (2.8%) LRRs were recorded as the first site of failure. Age, pathologic stage, and molecular subtype were identified as predictors of LRR. The major recurrence type was ipsilateral breast tumor recurrence, which mainly (83.6%) occurred ≤5y post surgery. In the overall population, ARR curves showed that relapse peaked in the first 2.5 years. Patients with regional nodal recurrence, shorter RFI, and synchronous distant metastasis were associated with a poorer prognosis. HER2-positive disease had a higher rate of LRR events, more likely to have in-breast recurrence, and had an earlier relapse peak in the first 2 years after surgery. CONCLUSIONS: LRR risk following BCS is generally low in Chinese ethnicity. Different recurrence patterns after BCS were related to distinct clinical outcomes. Management of LRR should be largely individualized and tailored to the extent of disease, the molecular profile of the recurrence, and to baseline clinical variables.

[The effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator flap breast reconstruction].

Objective: To examine the effect of adjuvant radiotherapy on postoperative complications of immediate deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. Methods: Data was collected from 185 patients underwent immediate DIEP reconstruction during November 2006 to March 2020 Department of Breast surgery, Fudan University shanghai Cancer Center. All the patients were female, aging (43.0±7.8) years (range: 29 to 61 years). The series included with a total of 187 flaps (2 bilateral, 183 unilateral). Included patients were divided into 2 groups: immediate DIEP reconstruction requring or not requring post-mastectomy radiation therapy (71 cases (71 flaps) in PMRT group, 114 cases (116 flaps) in control group). The aesthetic outcome were measured by Kroll score system and compared between the groups by t test. The complications included partial flap loss, minor necrosis were analyzed between the groups by χ2 test, while the influence of the other correlation factors on complication occurrence was analyzed by Logistic analysis. Results: The controll groups showed higher aesthetic results (2.21±0.55 vs. 2.47±0.82, t=-2.593, P=0.010). Complication rate in PMRT group was higher than that in control group (19.7% (15/71) vs. 4.2% (4/116), χ²=15.079,P<0.01). The complication rate was not correlated with age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy. Conclusions: Correlation was observed between adiuvant radiotherapy and post-operative complication of the DIEP flap. However, the complication occurrence and aesthetic results remain in the acceptable range. The other factors such as age, body mass index, perforator number, neoadjuvant chemotherapy and adjuvant chemotherapy should not be considered as prognosis factor of post-operative complication of the DIEP flap.

A predictor of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer patients with the DNA repair genes.

BACKGROUND: We conducted this study to investigate the prevalence of potential chemo-response-related gene mutations in triple-negative breast cancer (TNBC) patients and to evaluate the potential relationship between these gene mutations and neoadjuvant chemotherapy response in TNBC patients. METHODS: One hundred sixty-two TNBC patients in Fudan University Shanghai Cancer Center who received NAC with 4 cycles of paclitaxel and carboplatin were enrolled in this study. Fifty-six pathological complete response (pCR) patients and 56 non-pCR patients were enrolled in this retrospective study for the training set. Clinical assessments of postoperative residual tumors were performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Forty chemo-response-related genes were screened in each tumor specimen by second-generation sequencing analysis. Fifty TNBC patients who received neoadjuvant chemotherapy with paclitaxel and carboplatin were enrolled in the validation group. RESULTS: Fifty-seven of 112 (50.9%) TNBCs contained at least one detected somatic mutation. As expected, TP53 mutation was the most common alteration, which was observed in 21.4% of patients. BRCA1, BRCA2, RET, PI3KCA, and PTEN mutations were each observed in 11.6%, 4.5%, 5.4%, 2.7% and 3.6% of all cases, respectively. No significant differences in any gene mutation frequency between pCR and non-pCR groups were identified. We found that the mutation status of 10 DNA repair genes involved in homologous recombination (HR) pathway successfully discriminated between responding and nonresponding tumors in the training group. Up to 18 patients who were mutation-positive experienced pCR compared to only 6 in the non-pCR group (P=0.006), and 75% the HR related gene mutation patients achieved pCR. In the validation group, TNBC patients with DNA repair gene mutations achieved 77.8% pCR. CONCLUSIONS: A subset of TNBC patients carry deleterious somatic mutations in 10 HR-related genes. The mutation status of this expanded gene panel is likely to effectively predict respond rate to neoadjuvant chemotherapy based on paclitaxel and carboplatin. Our findings need to be validated through follow-up studies in this and additional cohorts.

Multiple cancer susceptible genes sequencing in BRCA-negative breast cancer with high hereditary risk.

BACKGROUND: Hereditary factors contributed to breast cancer susceptibility. Low BRCA mutation prevalence was demonstrated in previous BRCA mutation screening in Chinese breast cancer patients. Multiple-gene sequencing may assist in discovering detrimental germline mutation in. BRCA: negative breast cancers. METHODS: A total of 384 Chinese subjects with any two of high-risk factors were recruited and screened by next-generation sequencing (NGS) for 30 cancer susceptible genes. Variants with a truncating, initiation codon or splice donor/acceptor effect, or with pathogenicity demonstrated in published literature were classified into pathogenic/likely-pathogenic mutations. RESULTS: In total, we acquired 39 (10.2%) patients with pathogenic/likely-pathogenic germline mutations, including one carrying two distinct mutations. Major mutant non-BRCA genes were MUTYH (n=11, 2.9%), PTCH1 (n=7, 1.8%), RET (n=6, 1.6%) and PALB2 (n=5, 1.3%). Other mutant genes included TP53 (n=3, 0.8%), RAD51D (n=2, 0.5%), CHEK2 (n=1, 0.3%), BRIP1 (n=1, 0.3%), CDH1 (n=1, 0.3%), MRE11 (n=1, 0.3%), RAD50 (n=1, 0.3%) and PALLD (n=1, 0.3%). A splicing germline mutation, MUTYH c.934-2A>G, was a hotspot (9/384, 2.3%) in Chinese breast cancer. CONCLUSIONS: Among BRCA-negative breast cancer patients with high hereditary risk in China, 10.2% carried mutations in cancer associated susceptibility genes. MUTYH and PTCH1 had relatively high mutation rates (2.9% and 1.8%). Multigene testing contributes to understand genetic background of BRCA-negative breast cancer patients with high hereditary risk.

[Current trend of breast cancer neoadjuvant treatment in China: a cross-sectional study].

Objective: To investigate the current trend of breast cancer neoadjuvant therapy and provide reference for the improvement of breast cancer clinical guideline in the future. Methods: Questionnaires of cross-sectional survey were sent to 110 hospitals (breast cancer surgery quantity surpassing 200) between July 2018 and September 2018. The stages and subtypes, therapeutic regimen, treatment assession, operation choice and preforming of patients underwent neoadjuvant therapy were recorded. Results: Neoadjuvant treatment has been performed in all of the 110 hospitals. The total number of breast patients underwent neoadjuvant therapy was about 14 550 (17.0% in surgical patients) in 2017. For all of the neoadjuvant patients, the proportion of stageⅡ patients was less than 30% in 81 hospitals, and the proportion of stage Ⅲ was more than 50% in 84 hospitals. The numbers of estrogen receptor (ER) (+ )/human epidermal growth factor receptor-2 (HER-2) (-), ER (-)/HER-2 (+ ) and triple negative subtype breast cancer patients were 3 550 (24.4%), 6 024 (41.4%) and 4 991 (34.3%), respectively. Patient's scruples of relatively delayed operation and weak will of breast conservation after neoadjuvant therapy were the majority reasons for neoadjuvant therapy restriction. Anthracycline followed by taxane was the most usual neoadjuvant therapeutic regimens in 53.6% hospitals, and anthracycline plus taxane was the first choice in 42.7% hospitals. Chemotherapy with targeting therapy was recommended to HER-2 positive neoadjuvant patients in 80.9% hospitals. To assess treatment outcome of neoadjuvant treatment, 42.7% hospitals used MRI in more than 50% patients while the usage rate of MRI was less than 20% in 37.3% hospitals. The proportions of hospital using repeat-marking, tattoo and metal clip as the first method to identify the primary tumor region and lymph nodes were 60.0%, 29.1% and 10.9%, respectively. Breast-conservation rate after neoadjuvant therapy was less than 20% in 87.3% hospitals. Conclusions: Neoadjuvant therapy for breast cancer is widely performed in most hospitals in China, while the proportion of neoadjuvant treatment in patients with operable breast cancer is still low. Meanwhile, the idea of achieving de-escalation operation through neoadjuvant treatment is not promoted and the therapeutic evaluation method of neoadjuvant treatment needs further studies to improve.

Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing.

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.

Perineal stapled prolapse resection for external rectal prolapse: a systematic review and meta-analysis.

AIM: Rectal prolapse is an uncommon but debilitating pelvic floor disorder that significantly decreases the quality of life of affected patients. Perineal stapled prolapse resection is a relatively new perineal approach that offers an promising alternative technique in the surgical management of rectal prolapse. It appears to be a simple, reproducible and efficient method. However, long-term outcomes are limited. The aims of this review are to assess the safety and effectiveness of perineal stapled prolapse resection in the management of rectal prolapse. METHOD: A systematic review of all articles describing this approach was searched using MEDLINE, Embase, PubMed, Cochrane, Scopus, Web of Science and China National Knowledge Infrastructure. Included in this review were all randomized and nonrandomized prospective and retrospective studies reporting patients (aged 16 years and older) with complete rectal prolapse who underwent perineal stapled prolapse resection for the surgical treatment of the rectal prolapse. RESULTS: A total of 408 patients across 20 articles were included. There were 58 cases of recurrence out of 368 patients over a median length of follow-up of 18 months (interquartile range 12-34 months). The total weighted overall recurrence was 12%. There were 51 cases of postoperative complications in 350 cases, bleeding being the most common complication. CONCLUSION: The recurrence rate is comparable to those of the well-established Altemeier and Delorme procedures. However, given the heterogeneity of studies and variations in lengths of follow-up, further randomized prospective studies are needed to adequately compare this technique against other procedures for complete rectal prolapse.

LncRNA MIAT stimulates oxidative stress in the hypoxic pulmonary hypertension model by sponging miR-29a-5p and inhibiting Nrf2 pathway.

OBJECTIVE: To elucidate the potential biological functions of long non-coding RNA (lncRNA) MIAT in the development of hypoxic pulmonary hypertension (HPH) and the underlying mechanism. MATERIALS AND METHODS: Twenty Sprague Dawley (SD) rats were randomly assigned into normoxia group (n=10) and hypoxia group (n=10), respectively. In vivo HPH model in rats was established by hypoxic induction. Expression levels of MIAT and miR-29a-5p in rats were detected. Meanwhile, hemodynamic indicators in rats were examined. In vitro HPH model was conducted in hypoxia-induced HPAECs. The interaction between MIAT and miR-29a-5p was assessed by Dual-Luciferase reporter assay. Moreover, their regulatory effects on viability, migratory ability, oxidative stress, and the Nrf2 pathway in hypoxia-induced HPAECs were examined. RESULTS: MIAT was upregulated in both in vivo and in vitro HPH models, while miR-29a-5p was downregulated. Knockdown of MIAT suppressed viability, migratory ability, and oxidative stress in hypoxia-induced HPAECs. MiR-29a-5p was the target gene binding MIAT, and silence of miR-29a-5p partially relieved the inhibitory effects of MIAT on the above regulations in HPAECs. CONCLUSIONS: MIAT promotes proliferative and migratory abilities, as well as oxidative stress in hypoxia-induced HPAECs by targeting miR-29a-5p, thus aggravating the development of HPH.

[Research progress of relationship between vitamin K and type 2 diabetes].

Objective: To systematically review research on the association between vitamin K and type 2 diabetes and diabetes-related biomarkers in humans, and evaluate the role of vitamin K in the prevention of type 2 diabetes. Methods: "Vitamin K", "type 2 diabetes" and related terms were searched in PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang Med Online up to November 2018. Results: A total of 1 Chinese and 12 English articles were included. Among 6 observational studies, 5 of them showed that higher dietary vitamin K intake and plasma vitamin K level were associated with the decrease of the risk of type 2 diabetes. Among 6 clinical intervention studies, 5 of them indicated that the supplementation of vitamin K(1) or K2 could have positive influence on insulin metabolism. One Mendelian randomization study showed higher circulation vitamin K level might reduce the risk of type 2 diabetes. Conclusion: Vitamin K plays an important role in the prevention and control of type 2 diabetes, which may be related to the improvement of insulin metabolism and blood glucose level.

[Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China].

Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus (2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces (autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months-17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted >3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 10%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate (19%, 4/21), procalcitonin (4%,1/28), liver enzyme (22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions: In this case series, 2019-nCoV infection in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis of 2019-nCoV infection. After general treatment, the short-term prognosis is good.