Revisiting tumor angiogenesis:vessel co-option,vessel remodeling,and cancer cell-derived vasculature formation

Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen,nutrients,and other essential factors.The well-known vascular endothelial growth factor(VEGF) signaling is crucial for sprouting angiogenesis as well as recruitment of circulating progenitor endothelial cells to tumor vasculature,which has become therapeutic targets in clinical practice.However,the survival benefits gained from targeting VEGF signaling have been very limited,with the inevitable development of treatment resistance.In this article,we discuss the most recent findings and understanding on how solid tumors evade VEGF-targeted therapy,with a special focus on vessel co-option,vessel remodeling,and tumor cell-derived vasculature establishment.Vessel co-option may occur in tumors independently of sprouting angiogenesis,and sprouting angiogenesis is not always required for tumor growth.The differences between vessel-like structure and tubule-like structure formed by tumor cells are also introduced.The exploration of the underlying mechanisms of these alternative angiogenic approaches would not only widen our knowledge of tumor angiogenesis but also provide novel therapeutic targets for better controlling cancer growth and metastasis.

A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China

Matrix metalloproteinase 2(MMP2) has been shown to play an important role in several steps of cancer development.The-1306C/T polymorphism of the MMP2 gene displays a strikingly lower promoter activity than the T allele,and the CC genotype in the MMP2 promoter has been reported to associate with the development of several cancers.To assess the contribution of the MMP2-1306C/T polymorphism to the risk of nasopharyngeal carcinoma(NPC),we conducted a case-control study and analyzed MMP2 genotypes in 370 patients with NPC and 390 frequency-matched controls using real-time PCR-based TaqMan allele analysis.We found that subjects with the CC genotype had an increased risk(OR = 1.55,95% CI = 1.05-2.27) of developing NPC compared to those with the CT or TT genotypes.Furthermore,we found that the risk of NPC was markedly increased in subjects who were smokers(OR = 15.04,95% CI = 6.65-33.99),heavy smokers who smoked ≥20 pack-years(OR = 18.66,95% CI = 7.67-45.38),or young(<60 years) at diagnosis(OR = 1.52,95% CI = 1.01-2.29).Our results provide molecular epidemiological evidence that the MMP2-1306C/T promoter polymorphism is associated with NPC risk,and this association is especially noteworthy in heavy smokers.

Factors associated with upstaging in patients preoperatively diagnosed with ductal carcinoma in situ by core needle biopsy

Objective: Patients preoperatively diagnosed with ductal carcinoma in situ(DCIS) by core needle biopsy(CNB) exhibit a significant risk for upstaging on final pathology, which leads to major concerns of whether axillary staging is required at the primary operation. The present study aimed to identify clinicopathological factors associated with upstaging in patients preoperatively diagnosed with DCIS by CNB.Methods: The present study enrolled 604 patients(cN0 M0) with a preoperative diagnosis of pure DCIS by CNB, who underwent axillary staging between August 2006 and December 2015, at Fudan University Shanghai Cancer Center(Shanghai, China).Predictive factors of upstaging were analyzed retrospectively.Results: Of the 604 patients, 20.03%(n = 121) and 31.95%(n = 193) were upstaged to DCIS with microinvasion(DCISM) and invasive breast cancer(IBC) on final pathology, respectively. Larger tumor size on ultrasonography(> 2 cm) was independently associated with upstaging [odds ratio(OR) 1.558, P = 0.014]. Additionally, patients in lower breast imaging reporting and data system(BI-RADS) categories were less likely to be upstaged(4 B vs. 5: OR 0.435, P = 0.002;4 C vs. 5: OR 0.502, P = 0.001). Overall,axillary metastasis occurred in 6.79%(n = 41) of patients. Among patients with axillary metastasis, 1.38%(4/290), 3.31%(4/121)and 17.10%(33/193) were in the DCIS, DCISM, and IBC groups, respectively.Conclusions: For patients initially diagnosed with DCIS by CNB, larger tumor size on ultrasonography(> 2 cm) and higher BIRADS category were independent predictive factors of upstaging on final pathology. Thus, axillary staging in patients with smaller tumor sizes and lower BI-RADS category may be omitted, with little downstream risk for upstaging.

The effect of an early oral stimulation program on oral feeding of preterm infants

Purpose:To evaluate the effect of an oral stimulation program on preterm infants.Methods:Preterm infants(n=72)were randomly assigned to experimental and control groups.Controls(n=36)received routine care while the experimental group(n=36)received oral stimulation in addition to routine care.Postmenstrual age,total intake volume,body weight,the transition time from initiation of oral feeding to full oral feeding and feeding efficiency were calculated.Results:Postmenstrual age and full oral feeding weight were significantly lower in the experimental group(p<0.05).The time from initiation of oral feeding to full oral feeding was significantly shorter in the experimental group(p<0.05)while feeding efficiency was higher in the experimental group(p<0.05)compared to controls.No significant differences existed in hospital stay length or weight gain rate.Conclusions:An early oral stimulation program is beneficial in preterm infants.

不同矫正胎龄早产儿使用更昔洛韦的安全性观察

目的观察早产儿使用更昔洛韦治疗巨细胞病毒感染的安全性。方法回顾分析2017年10月1日—2021年10月1日在复旦大学附属儿科医院新生儿科住院且使用更昔洛韦治疗巨细胞病毒感染的早产儿临床资料,比较矫正胎龄(PMA)<37周或≥37周患儿使用更昔洛韦后中性粒细胞绝对值、血小板数、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、血清肌酐(SCr)等安全性指标的变化。结果共纳入40例患儿,开始治疗时PMA<37周的25例,PMA≥37周的15例。23例更昔洛韦剂量为6 mg·kg^(-1),q12h,17例更昔洛韦剂量为5 mg·kg^(-1),q12h。不同PMA组患儿中性粒细胞减少发生风险差异无统计学意义(P>0.05),但3~4级中性粒细胞减少症发生风险差异显著[发生率分别为24.0%(6/25)和0%(0/15),P<0.05]。不同PMA组患儿血小板减少发生风险无明显差异(P>0.05),但PMA<37周的患儿发生1例严重血小板减少,而PMA≥37周组无;PMA<37周的患儿,更昔洛韦剂量6 mg·kg^(-1)发生血小板下降风险更高。不同PMA患儿肝酶升高发生风险无显著差异(P>0.05)。1例PMA<37周患儿SCr明显上升,但可能由合并的失血性休克引起。不同PMA患儿SCr上升发生风险差异无统计学意义(P>0.05)。结论不同PMA的早产儿使用更昔洛韦过程中,发生中性粒细胞减少、血小板降低和肝酶升高的风险无显著差异。开始治疗时,PMA<37周患儿重度及以上中性粒细胞减少发生风险高于PMA≥37周者。且PMA<37周患儿给予6 mg·kg^(-1)剂量相比5 mg·kg^(-1)发生血小板降低的风险更高。因此,在密切监测不良反应的同时,仍需优化更昔洛韦在不同PMA早产儿中的给药方案,以确保用药的安全性。

Long-term effect of vasectomy on spermatogenesis in ,en： a morphometric study

Spermatogenic damage may occur after vasectomy, and the damage is pressure mediated, occurring when the occluded reproductive tract is unable to accommodate additional sperm produced by the testis. This study aimed to determine the long-term effect of vasectomy on spermatogenesis in humans and clarify how the balance between sperm production in the testis and sperm storage in or removal from the tract might be maintained. During inguinal hernia repair, an open biopsy was performed to obtain testicular tissue blocks from 51 Chinese men （aged ≥ 50 years）, of whom 25 （control group） had not undergone vasectomy and 26 （vasectomized group） had undergone bilateral vasectomy 22-42 years before. Methacrylate resin-embedded testicular sections were made, and morphometric studies were performed using light microscopy. In addition, sizes of the testis and epididymis were estimated with ultrasonography. The testicular tissue blocks obtained from one control and seven vasectomized men consisted almost completely of connective tissue. In the other 43 men, significant differences were not found between the two groups in the testicular or epididymal size, qualitative histology or quantitative parameters including the mean diameter or volume fraction of the seminiferous tubules. In conclusion, sperm production and sperm storage/removal reached a static equilibrium after vasectomy, likely due to spermatogenic degeneration or less sperm production as a result of aging or due to vasectomy-induced testicular （interstitial） fibrosis. Thus, complications that might occur in association with overproduction of sperm and distension of the tract would disappear or be relieved with time.

Epitaxial fabrication of two-dimensional TiTe_2 monolayer onAu(111) substrate with Te as buffer layer

Two-dimensional(2 D) materials provide a platform to exploit the novel physical properties of functional nanodevices.Here, we report on the formation of a new 2 D layered material, a well-ordered monolayer TiTe_2, on a Au(111) surface by molecular beam epitaxy(MBE). Low-energy electron diffraction(LEED) measurements of the samples indicate that the TiTe_2 film forms(√3 ×√7) superlattice with respect to the Au(111) substrate, which has three different orientations. Scanning tunneling microscopy(STM) measurements clearly show three ordered domains consistent with the LEED patterns.Density functional theory(DFT) calculations further confirm the formation of 2 H-TiTe_2 monolayer on the Au(111) surface with Te as buffer layer. The fabrication of this 2 D layered heterostructure expands 2 D material database, which may bring new physical properties for future applications.

NBN-doped nanographene embedded with five-and seven-membered rings on Au(111)surface

Nanographenes(NGs)can be embedded with predesigned dopants or nonhexagonal rings to tailor the electronic properties and provide ideal platforms to study the unique physical and chemical properties.Here,we report the on-surface synthesis of NBN-doped NG embedded with five-and seven-membered rings(NBN-575-NG)on Au(111)from a oligophenylene precursor preinstalled with a NBN unit and a heptagonal ring.Scanning tunneling microscopy and non-contact atomic force microscopy images elucidate the intramolecular cyclodehydrogenation and the existence of the five-and seven-membered rings.Scanning tunneling spectroscopy spectra reveal that the NBN-575-NG is a semiconductor,which agrees with the density functional theory calculation results on a freestanding NBN-575-NG with the same structure.This work provides a feasible approach for the on-surface synthesis of novel NGs containing non-hexagonal rings.

Adsorption structure of macrocyclic energetic molecule DOATF on Au(111)

Furazan macrocyclic compound 3,4:7,8:11,12:15,16-tetrafurazan-1,9-dioxazo-5,13-diazocyclohexadecane(DOATF)is an ideal energetic material with high heat of formation.Here,using scanning tunneling microscopy(STM)and noncontact atomic force microscopy(nc-AFM),we investigated the adsorption structure of DOATF molecules on Au(111)surface,which shows the four furanzan rings in the STM images and a bright protrusion off the center of the molecule in the nc-AFM images.Combined with density functional theory(DFT)calculations,we confirmed that the bright feature in the nc-AFM images is an N-O coordinate bond pointing upwards in one of the two azoxy groups;while the other N-O bond pointing towards the Au(111)surface.Our work contributes for a deeper understanding of the adsorption structure of macrocyclic compounds,which would promote the designing of DOATF-metal frameworks.

Resolving Deep Sub-Wavelength Scattering of Nanoscale Sidewalls Using Parametric Microscopy

The quantitative optical measurement of deep sub-wavelength features with sub-nanometer sensitivity addresses the measurement challenge in the semiconductor fabrication process.Optical scatterings from the sidewalls of patterned devices reveal abundant structural and material information.We demonstrated a parametric indirect microscopic imaging(PIMI)technique that enables recovery of the profile of wavelength-scale objects with deep sub-wavelength resolution,based on measuring and filtering the variations of far-field scattering intensities when the illumination was modulated.The finite-difference time-domain(FDTD)numerical simulation was performed,and the experimental results were compared with atomic force microscopic(AFM)images to verify the resolution improvement achieved with PIMI.This work may provide a new approach to exploring the detailed structure and material properties of sidewalls and edges in semiconductor-patterned devices with enhanced contrast and resolution,compared with using the conventional optical microscopy,while retaining its advantage of a wide field of view and relatively low cost.

Characteristic metabolic and microbial profiles in acute ischemic stroke patients with phlegm-heat pattern

Objective:To explore the characteristics of plasma metabolites,feces gut microbiota and the crosstalk between gut microbiota and host metabolism in patients with acute ischemic stroke and phlegm-heat pattern(AIS-PHP).Methods:The metabolic and microbiome profiles of 20 AIS-PHP patients and 20 healthy controls(HCs)were analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS)-based metabolomics and 16s rDNA sequencing,respectively.The covariation between LC-MS/MS-based metabolite data and 16s rDNA sequence data was presented.Results:Distinct alterations in the plasma metabolic phenotype of AIS-PHP patients were found,in which 16 metabolites differed significantly between the AIS-PHP patients and the HCs.These metabolites represented 17 different metabolic pathways,including amino acid metabolism,lipid metabolism,and nucleotide metabolism.Additionally,significant alterations of gut microbiota composition and taxon were revealed at the phylum level between the AIS-PHP patients and the HCs.In AIS-PHP,Bacteroidetes,Firmicutes,and Proteobacteria dominated.Moreover,some microbes that differed between the 2 groups manifested a sole association with certain metabolites,such as the connection between Bacteroides and inosine and between Lachnospiraceae_unclassified and hypoxanthine.Conclusion:The present study preliminarily investigated the metabolomic and gut microbiome characteristics of AIS-PHP patient indicators.The link between metabolic and microbial dysbiosis in AIS-PHP sheds new light on the function of gut microbiota and associated metabolomics in the pathogenesis of the disease.

Primary intestinal lymphangiectasia presenting as limb convulsions:A case report

BACKGROUND Primary intestinal lymphangiectasia(PIL)is a rare protein-losing enteropathy characterized by abnormally dilated lymphatic structures,resulting in leakage of lymph(rich in protein,lymphocytes,and fat)from the intestinal mucosal and submucosal layers and thus hypoproteinemia,lymphopenia,hypolipidemia,and pleural effusion.CASE SUMMARY A 19-year-old Chinese male patient complained of recurrent limb convulsions for the last 1 year.Laboratory investigations revealed low levels of calcium and magnesium along with hypoproteinemia and high parathyroid hormone levels,whereas gastroscopy exhibited chronic non-atrophic gastritis and duodenal lymphatic dilatation.Subsequent gastric biopsy showed moderate chronic inflammatory cell infiltration distributed around a small mucosal patch in the descending duodenum followed by lymphatic dilatation in the mucosal lamina propria,which was later diagnosed as PIL.The following appropriate mediumchain triglycerides nutritional support significantly improved the patient’s symptoms.CONCLUSION Since several diseases mimic the clinical symptoms displayed by PIL,like limb convulsions,low calcium and magnesium,and loss of plasma proteins,it is imperative to conduct a detailed analysis to avoid any misdiagnosis while pinpointing the correct clinical diagnosis and simultaneously ruling out other clinical aspects in the reported cases without any past disease history.A careful assessment should always be made to ensure an accurate diagnosis in a timely manner so that the patient can be delivered quality health services for a positive health outcome.

Clinical Observation of Zhuang Medicine Yangxue Xiaozheng Decoction in Treating the Combined Endometriosis of Dampness and Blood Stasis in Guangxi

Objective:To explore the clinical effects of Zhuang Medicine Yangxue Xiaozheng Decoction in treating the combined Ems of dampness and blood stasis in Guangxi;Methods:100 patients with endometriosis treated in Lili Clinic of Famous Doctor,Guangxi International Zhuang Medicine Hospital from Mach 2016 to May 2017 were chosen as the research object.According to the random grouping method,patients were randomly divided into the treatment group(The Zhuang Medicine Yangxue Xiaozheng Decoction(ZYF)Group)and the control group(Chinese patent medicine SanJieZhenTongJiaoNang(SJZT)group with 50 cases in each group.After treatment,the TCM syndrome score,changes in pelvic mass size,hepatocyte growth factor(HGP)levels,and clinical effects before and after treatment were evaluated.Results:After two courses of treatment,the total effective rate of patients in the ZYF group was 88%,which were significantly better than 70%of the SJZT group.The difference was statistically significant(P<0.05).Conclusion:With a significant effect on patients with the combined Ems of dampness and blood stasis in Guangxi,Zhuang Medicine Yangxue Xiaozheng Decoction can improve the uterine cavity mass and reduce serum HGP level.

Delivery room resuscitation intensity and associated neonatal outcomes of 24^(+0)-31^(+6) weeks'preterm infants in China:a retrospective cross-sectional study

Background The aim of this study was to review current delivery room(DR)resuscitation intensity in Chinese tertiary neonatal intensive care units and to investigate the association between DR resuscitation intensity and short-term outcomes in preterm infants born at 24+0_31+6 weeks gestation age(GA).Methods This was a retrospective cross-sectional study.The source population was infants born at 24+0_31+6 weeks'GA who were enrolled in the Chinese Neonatal Network 2019 cohort.Eligible infants were categorized into five groups:(1)regular care;(2)oxygen supplementation and/or continuous positive airway pressure(O2/CPAP);(3)mask ventilation;(4)endotracheal intubation;and(5)cardiopulmonary resuscitation(CPR).The association between DR resuscitation and shortterm outcomes was evaluated by inverse propensity score-weighted logistic regression.Results Of 7939 infants included in this cohort,2419(30.5%)received regular care,1994(25.1%)received O,/CPAP,1436(18.1%)received mask ventilation,1769(22.3%)received endotracheal intubation,and 321(4.0%)received CPR in the DR.Advanced maternal age and maternal hypertension correlated with a higher need for resuscitation,and antenatal steroid use tended to be associated with a lower need for resuscitation(P<0.001).Severe brain impairment increased significantly with increasing amounts of resuscitation in DR after adjusting for perinatal factors.Resuscitation strategies vary widely between centers,with over 50%of preterm infants in eight centers requiring higher intensity resuscitation.Conclusions Increased intensity of DR interventions was associated with increased mortality and morbidities in very preterm infants in China.There is wide variation in resuscitative approaches across delivery centers,and ongoing quality improvement to standardize resuscitation practices is needed.

Species clarification of the prize medicinal Ganoderma mushroom“Lingzhi”

“Lingzhi”is a mushroom that has been renowned in China for more than 2,000 years because of its claimed medicinal properties plus its symbolic fortune.“Lingzhi”has high economic value mostly as a dietary supplement in the modern market especially in East Asia,and its medicinal functions have become a hot study topic.For over a century,the highly prized medicinal fungus,known as“Lingzhi”in East Asia,has been assigned to Ganoderma lucidum,a species originally described from Europe.Molecular studies in recent years have revealed that the commercially cultivated‘G.lucidum’(“Lingzhi”)in East Asia is a different species from the true G.lucidum.The present study aims to clarify the species identity of“Lingzhi”based on morphological studies and analysis of rDNA nuc-ITS sequences,and additional gene fragments of mt-SSU,RPB1,RPB2,and TEF1-αof“Lingzhi”were provided.All Ganoderma species that mostly resemble“Lingzhi”in phylogeny and/or morphology were included for analysis.We propose a new species G.lingzhi for“Lingzhi”,which has an East Asia distribution.The most striking characteristics which differentiate G.lingzhi from G.lucidum are the presence of melanoid bands in the context,a yellow pore surface and thick dissepiments(80–120μm)at maturity.G.curtisii is most closely related to G.lingzhi in phylogeny and is from North America.Ganoderma flexipes,G.multipileum,G.sichuanense,G.tropicum and‘G.tsugae’,are also closely related with G.lingzhi and are reported from China.These species are compared and discussed.‘Ganoderma tsuage’reported from China is determined as conspecific with G.lucidum,hence the distribution of G.lucidum extends from Europe to northeastern China.

Trend and causes of neonatal mortality in a level Ⅲ children's hospital in Shanghai: a 15-year retrospective study

Background To determine the trend and causes of neonatal mortality in a large level Ⅲ neonatal intensive care unit in Shanghai during a 15-year period. Methods This is a retrospective, single-centered study. All neonates who died during the period from January 1, 1999 to December 31, 2013 at Children's Hospital of Fudan University were included. We extracted relevant clinical information from their medical records, analyzed neonatal mortality rate and the characteristics of these patients, and compared neonatal deaths between different periods and populations. Results Among a total of 50,957 admissions during the study period, there were 929 neonatal deaths. The neonatal mortality rate was 1.82%. Trends in neonatal mortality rate showed an increase in the period from 1.0% in 2003 to 2.2% in 2013. The main causes of neonatal mortality were complications of preterm birth (33.6%), congenital anomalies (21.3%), infections (12.6%), and birth asphyxia (9.1%). The proportions of complications of preterm birth (P < 0.001) and congenital anomalies (P = 0.018) increased yearly, while the proportions of birth asphyxia (P < 0.001) and infections (P < 0.001) decreased. Proportions of deaths caused by birth asphyxia (P = 0.005) and infections (P < 0.001) were both higher in the migrating population than in the permanent residents. Conclusions Neonatal mortality rate increased from 2003 to 2013 in our study. The proportion of preterm infants in neonatal deaths also increased within the same period. Complications of preterm birth were the main cause of neonatal mortality and the percentage increased year by year. Neonates in the migrating population appeared to be at a higher risk of death during the neonatal period compared to those in the permanent residents, and efforts should be made towards improving perinatal care to prevent infections and birth asphyxia in this vulnerable population.

Group B Streptococcus causes severe sepsis in term neonates:8 years experience of a major Chinese neonatal unit

Background:In contrast to industrialized countries,the clinical characteristics of neonatal sepsis caused by Group B Streptococcus (GBS) are largely unexplored in China.Methods:A retrospective case series study was performed at a high-capacity neonatal unit in Shanghai,China from January 2008 to December 2015.Clinical characteristics of neonates with culture-proven GBS sepsis and antibiotic susceptibility of isolated strains were analyzed.Results:Forty-three term neonates were included during the study period.The majority (74.4%) had early-onset sepsis with symptoms of respiratory distress.Meningitis was significantly more common in lateonset sepsis than in early-onset sepsis (81.5% vs.18.8%,P<0.0001).Approximately one third of all patients (n=16)developed severe sepsis,defined as sepsis with organ dysfunctions,and respiratory dysfunction/failure was the most common (32.6%).The in-hospital mortality rate of GBS sepsis was 4.7%.Neonates who progressed to severe sepsis had significantly lower pH level at the onset of symptoms than those who did not (7.26±0.12 vs.7.39±0.05,P=-0.006).Treatment of severe GBS sepsis required lots of medical resources including extracorporeal membrane oxygenation.All tested GBS strains were susceptible to penicillin,but the rate of resistance to clindamycin (84.0%) and erythromycin (88.0%) was high.Conclusions:GBS as a pathogen for neonatal sepsis has been receiving little attention in China.Our data demonstrated that GBS sepsis was likely to be fulminant.Early recognition followed by antibiotics and adequate supportive therapies was critical for successful treatment.Chinese clinicians should be aware of GBS infection when treating neonatal sepsis,especially in the absence of universal maternal GBS screening.

Use of antenatal corticosteroids among infants with gestational age at 24 to 31 weeks in 57 neonatal intensive care units of China: a cross-sectional study

Background:Antenatal corticosteroids(ACS)can significantly improve the outcomes of preterm infants.This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units(NICU)and to explore perinatal factors associated with ACS use,using the largest contemporary cohort of very preterm infants in China.Methods:This cross-sectional study enrolled all infants born at 24^(+0)to 31^(+6)weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st,2019 to December 30th,2019.The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery.Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage.Results:A total of 7828 infants were enrolled,among which 6103(78.0%)infants received ACS.ACS use rates increased with increasing gestational age(GA),from 177/259(68.3%)at 24 to 25 weeks’gestation to 3120/3960(78.8%)at 30 to 31 weeks’gestation.Among infants exposed to ACS,2999 of 6103(49.1%)infants received a single complete course,and 33.4%(2039/6103)infants received a partial course.ACS use rates varied from 30.2%to 100%among different hospitals.Multivariate regression showed that increasing GA,born in hospital(inborn),increasing maternal age,maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS.Conclusions:The use rate of ACS remained low for infants at 24 to 31 weeks’gestation admitted to Chinese NICUs,with fewer infants receiving a complete course.The use rates varied significantly among different hospitals.Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.

Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman＇s syndrome

Asherman's syndrome(AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells(BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.

Variations in length of stay among survived very preterm infants admitted to Chinese neonatal intensive care units

Background This study aimed to describe length of stay(LOS)to discharge and site variations among very preterm infants(VPIs)admitted to 57 Chinese neonatal intensive care units(NICUs)and to investigate factors associated with LOS for VPIs.Methods This retrospective multicenter cohort study enrolled all infants<32 weeks’gestation and admitted to 57 NICUs which had participated in the Chinese Neonatal Network,within 7 days after birth in 2019.Exclusion criteria included major congenital anomalies,NICU deaths,discharge against medical advice,transfer to non-participating hospitals,and missing discharge date.Two multivariable linear models were used to estimate the association of infant characteristics and LOS.Results A total of 6580 infants were included in our study.The overall median LOS was 46 days[interquartile range(IQR):35-60],and the median corrected gestational age at discharge was 36 weeks(IQR:35-38).LOS and corrected gestational age at discharge increased with decreasing gestational age.The median corrected gestational age at discharge for infants at 24 weeks,25 weeks,26 weeks,27-28 weeks,and 29-31 weeks were 41 weeks,39 weeks,38 weeks,37 weeks and 36 weeks,respectively.Significant site variation of LOS was identified with observed median LOS from 33 to 71 days in different hospitals.Conclusions The study provided concurrent estimates of LOS for VPIs which survived in Chinese NICUs that could be used as references for medical staff and parents.Large variation of LOS independent of infant characteristics existed,indicating variation of care practices requiring further investigation and quality improvement.