Cardiovascular disease is a health hazard to humans and systolic heart failure due to myocardial infarction is a major cause of death.It was previously thought that myocardial cells of the adult mammalian heart possess a limited ability to proliferate and self-renew.However,it has been widely reported that mammals have the ability to regenerate the myocardium,which is restricted to early postnatal life,and that it is strong enough to repair damaged heart tissue.The discovery of myocardial regeneration in neonatal hearts has provided an ideal animal model to investigate the mechanisms that affect myocardial regeneration,and many mechanisms that reverse myocardial cell cycle arrest and promote myocardial regeneration have been revealed.In this article,we review the factors affecting gene expression for myocardial regeneration(e.g.,ncRNAs and transcription factors),myocardial regeneration-related signaling pathways,and the regulation of myocardial regeneration by non-myocardial cells(e.g.,extracellular matrix,immune response,and epicardium)to provide directions for achieving myocardial regeneration after myocardial injury in adult mammals.

Objective:To investigate the clinical characteristics, treatment and prognosis of newly-treated patients with primary central nervous system lymphoma (PCNSL).Methods:Clinical data of 117 newly-treated PCNSL patients who were admitted to the First Hospital of Jilin University, the Fifth Medical Center of Chinese PLA General Hospital, Harbin Medical University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College from August 2009 to February 2018 were retrospectively analyzed. The patients' age, sex, Eastern Cooperative Oncology Group (ECOG) physical status (PS) score, pathological type, involvement of deep brain tissue, number of lesions, cerebrospinal fluid protein concentration, International Extranodal Lymphoma Study Group (IELSG) score, Memorial Sloan Kettering Cancer Center (MSKCC) score, treatment strategy, and response after the first-line therapy were analyzed using univariate and multivariate Cox proportional hazards models to identify the independent influencing factors for progression-free survival (PFS) and overall survival (OS) of PCNSL patients. Kaplan-Meier method was used for survival analysis.Results:In 117 newly-treated PCNSL patients, 59 cases (50.4%) presented with increased intracranial pressure or focal neurological symptoms at diagnosis; there were 65 cases (55.6%) with single lesions and 52 cases (44.4%) with multiple lesions; 1 patient (0.9%) had lymphoma of T-cell origin, and 116 cases (99.1%) had diffuse large B-cell lymphoma (DLBCL). Among 95 evaluable patients, 41 patients (43.2%) achieved complete remission (CR), 20 patients (21.1%) achieved partial remission (PR), 16 patients (16.8%) achieved stable disease (SD), and 18 patients (18.9%) had progressive disease (PD). In 117 patients with median follow-up of 66.0 months (95% CI 57.9-74.1 months), the median PFS and OS were 17.4 months (95% CI 11.5-23.3 months) and 45.6 months (95% CI 20.1-71.1 months), respectively. The 2-, 3- and 5-year PFS rates were 41.2%, 28.6% and 19.3%, and OS rates were 63.7%, 52.4% and 46.3%, respectively. Univariate Cox regression analysis showed that baseline high-risk MSKCC score group was an adverse prognostic factor for PFS ( P = 0.037), and the first-line chemotherapy with ≥4 cycles of high-dose methotrexate (HDMTX), HDMTX in combination with rituximab, ≥4 cycles of rituximab in combination with HDMTX, and achieving CR or ≥PR after the first-line treatment reduced the risk of disease progression and prolonged the PFS time (all P <0.01); age >60 years old, ECOG-PS score of 2-4 points, elevated cerebrospinal fluid protein concentration, high-risk IELSG score, and high-risk MSKCC score were adverse prognostic factors for OS, and ≥4 cycles of HDMTX and achieving CR or ≥PR after the first-line treatment were favorable factors for OS. Multivariate Cox regression analysis verified that rituximab in combination with HDMTX (yes vs. no: HR = 0.349, 95% CI 0.133-0.912, P = 0.032) and achieving ≥PR after the first-line chemotherapy (yes vs. no: HR = 0.028, 95% CI 0.004-0.195, P < 0.001) were independent favorable factors for PFS; age >60 years old (>60 years old vs. ≤60 years old: HR = 10.878, 95% CI 1.807-65.488, P = 0.009) was independent unfavorable factor for OS, while ≥4 cycles of HDMTX treatment (≥4 cycles vs. <4 cycles: HR = 0.225, 95% CI 0.053-0.947, P = 0.042) was independent favorable factor for OS. Conclusions:The older the PCNSL patients at initial treatment, the worse the prognosis. Intensive and continuous treatment for achieving deeper remission may be the key for improving the outcome of PCNSL patients.

The study was a retrospective study. The clinical data of 866 patients with IgA nephropathy (IgAN) in Beijing Anzhen Hospital, Capital Medical University from March 2010 to March 2021 were analyzed, to investigate the clinical pathology and renal prognosis of IgAN patients with intrarenal arteriolosclerosis, and to preliminarily explore whether abnormal activation of complement system is involved in the injury of arteriolosclerosis. The patients were divided into renal arteriolar lesions group and non-renal arteriolar lesions group according to the renal histopathology, and the differences of clinical pathological manifestations, prognosis between the two groups were compared. The results showed that, compared with the non-renal arteriolar lesions group ( n=236), IgAN patients in the renal arteriolar lesions group ( n=630) had higher proportions of hypertension and malignant hypertension, higher levels of urinary albumin-creatinine ratio, 24-hour urine protein quantification and serum uric acid, lower estimated glomerular filtration rate, and more severe MEST-C lesions of the Oxford classification (all P < 0.05). Cox regression analysis results showed that intrarenal arteriolosclerosis was the independent risk factor affecting the progression of IgAN to ESRD ( HR=6.437, 95% CI 2.013-20.585, P=0.002). Renal histopathology showed that the deposition of complement C3c on the wall of intrarenal arterioles in the renal arteriolar lesions group ( n=98) was stronger than that in non-renal arteriolar lesions group ( n=18, P < 0.05). IgAN patients with renal arteriolosclerosis present with serious clinical and pathological manifestations, and renal prognosis. Abnormal activation of complement system may be involved in the pathogenesis of intrarenal arteriolosclerosis.

Extracellular vesicles (EVs)-based cell-free strategy has shown therapeutic potential in tissue regeneration. Due to their important roles in intercellular communications and their natural ability to shield cargos from degradation, EVs are also emerged as novel delivery vehicles for various bioactive molecules and drugs. Accumulating studies have revealed that EVs can be modified to enhance their efficacy and specificity for the treatment of many diseases. Engineered EVs are poised as the next generation of targeted delivery platform in the field of precision therapy. In this review, the unique properties of EVs are overviewed in terms of their biogenesis, contents, surface features and biological functions, and the recent advances in the strategies of engineered EVs construction are summarized. Additionally, we also discuss the potential applications of engineered EVs in targeted therapy of cancer and damaged tissues, and evaluate the opportunities and challenges for translating them into clinical practice.

Objective:To evaluate the cerebral infarct volume and the nerve fiber connectivity between cortical and neurogenesis-related regions in the mouse model of reperfusion after middle cerebral artery occlusion (MCAO) by 11.7 Tesla(11.7 T) magnetic resonance imaging (MRI).Methods:MCAO models were established in SPF grade adult male C57BL/6 mice using the suture-occluded method.MRI scans were performed at 3 days before and 1 day after modeling.Infarct volumes were calculated, and nerve fiber tracking was performed on specific brain regions to analyze the nerve fiber number and the parameters of fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity (AD)and radial diffusivity(RD). SPSS 26.0 was used for statistical analysis, and paired t test was used to compare the data before and after modeling. Results:(1) After MCAO-induced ischemia, the infarct volume was up to (35.11±17.57)mm 3, and the FA value of the infarct area was significantly reduced compared with that of before modeling( t=4.73, P<0.01). (2) At the anterior-posterior(AP): + 1.2 mm section, the results of fiber tracking showed that compared with before modeling, the number of fiber bundles originating from the dorsal horn of the lateral sub-ventricle zone(SVZ)to the cortex reduced ((92 584.20±14 751.00) vs (59 815.60±6 752.46), t=4.87, P<0.01), and the number of fiber bundles projected to the infarcted area reduced ((107 671.40±10 497.57) vs (61 658.60±10 178.21), t=6.43, P<0.01). FA, AD, MD, and RD values were all decreased in different degrees( t=3.38-6.43, all P<0.05). (3) At the AP: -3.8 mm section, the number of fiber bundles originating from the dorsal horn of the SVZ to the cortex decreased (after modeling(96 944.00±18 331.09), before modeling(58 767.80±16 445.25), t=2.99, P<0.05), and the values of FA, AD, MD and RD decreased after ischemia ( t=7.30, 5.05, 6.74, 4.13, all P<0.05). Conclusion:The ultra-high field strength of 11.7 T MRI can accurately detect the following results that the number of nerve fiber bundles from the SVZ to the cortex or infarct area are both significantly reduced, and diffusion tensor parameters are consistently changed in mice after 1 day of ischemia-reperfusion.

A case of cicatricial female pattern hair loss was reported. A 36-year-old female patient presented with gradually aggravated hair loss for more than 10 years. Skin examination showed diffuse hair thinning on the scalp, thin and soft hairs, and some pencil eraser-sized areas of focal atrichia. TrichoScan examination revealed markedly decreased hair density on the forehead, variability in hair diameter greater than 20%, and increased proportions of vellus hairs. Dermoscopic examination showed increased numbers of vellus hairs, plenty of focal atrichia areas measuring 3 - 5 mm in diameter, loss of some follicular ostia, and confluent white dots. Histopathological examination of vertical and transverse scalp sections showed predominantly distributed miniaturized hair follicles with lichenoid folliculitis around the infundibulum and isthmus, concentrically layered perifollicular fibrosis, a marked decrease in the number of hair follicles compared with healthy people of the same age, increased proportions of vellus hairs, a large number of miniaturized hair follicles and follicular streamers, and formation of follicular micro-scars. The patient was diagnosed with cicatricial female pattern hair loss. She received topical treatment with 5% minoxidil liniment once a day, and alternate treatment with topical tacrolimus ointment and clobetasol propionate ointment, as well as oral spironolactone at a dose of 20 mg twice a day and compound glycyrrhizin capsules at a dose of 50 mg thrice a day. After half a year of treatment, there was no marked aggravation of hair loss, and the follow-up continued.

A case of fibrosing alopecia in a pattern distribution (FAPD) and its clinicopathological, dermoscopic and TrichoScan features were reported to improve the understanding of FAPD. A 23-year-old male patient presented with progressive hair loss on the forehead and top of the head for 10 years, local hair thinning and softening, and occasional scalp itching. Skin examination showed diffuse sparseness of hair from the forehead to the top of the head, frontal hairline recession, focal thinning and softening of hair, some follicular keratotic papules and perifollicular erythema on the alopecic area, with no obvious scales. TrichoScan examination revealed markedly decreased hair density and increased proportions of vellus hairs. Dermoscopy showed loss of some follicular ostia and confluent white dots. Histopathological examination of the scalp showed lichenoid lymphocytic infiltration around the infundibulum and isthmus of hair follicles, concentrically layered perifollicular fibrosis, hair follicle destruction, formation of follicular micro-scars, markedly increased variation in the diameter of residual follicles, and some vellus hairs. The patient was diagnosed with FAPD. FAPD is easily misdiagnosed as androgenetic alopecia, and early diagnosis and treatment are needed.

Objective: To compare diagnostic performance of traditional vertical section technique, horizontal section technique and modified Ho-Vert technique for classical lichen planopilaris. Methods: Clinical data were collected from patients with classical lichen planopilaris in Department of Dermatology, The Affiliated Wuxi People′s Hospital of Nanjing Medical University from January 1st 2015 to January 1st 2019. With the help of dermoscopy, 2 scalp specimens were obtained from each patient and sliced horizontally and vertically respectively by using modified Ho-Vert technique. The horizontal and vertical sections were read separately or simultaneously, and histopathological changes were observed. Results: Totally, 21 patients with classical lichen planopilaris were enrolled into this study, including 15 males and 6 females. Their age was 50.0 ± 13.6 years, and the average course of disease was 18 months. The patients mainly presented with multifocal or confluent patchy hair loss, and scalp atrophy, perifollicular hyperkeratosis, loss of follicular ostia, fibrous white dots and orbit sign were observed. On the horizontal sections, lichenoid lymphocytic infiltration around the infundibulum and isthmus of hair follicles and follicular micro-scars could be observed in all patients, and the dermo-epidermal interface could be seen in 7 patients. On the vertical sections, lichenoid lymphocytic infiltration around the infundibulum and isthmus of hair follicles only could be observed in 9 patients, follicular micro-scars could be seen in 4, and the dermo-epidermal interface could be observed in all patients. Moreover, the detection rates of interfollicular interface dermatitis, follicular keratotic plugs, lymphocytic infiltration around sebaceous glands, atrophy or disappearance of sebaceous glands and inflammatory infiltration around hair follicle bulbs were significantly different between the horizontal and vertical sections. In combination with clinical manifestations, 7 patients could be exactly diagnosed with lichen planopilaris according to findings from horizontal sections, and 9 could be diagnosed exactly according to findings from vertical sections, while 21 could be diagnosed exactly according to histopathological findings from both horizontal and vertical sections. Conclusion With the help of dermoscopy, modified Ho-Vert technique can improve the efficacy of pathological diagnosis of classical lichen planopilaris, by multidimensionally showing histopathological changes.

Alopecia is a common disease in dermatologic clinics.The diagnosis of some hair diseases does not rely on pathological examinations,and with the development of science and technology,the role of many new non-invasive detection instruments,such as dermoscopy,hair scanners and skin CT,is increasingly valued in the diagnosis and treatment of hair diseases.However,the role of pathological examination is still irreplaceable.Because of the particularity of hair diseases,hair pathology differs from common skin pathology in the aspects of scalp biopsy sites,biopsy methods and techniques,tissue-slicing methods and pathological report content.This review systematically discusses the role of scalp pathological biopsy in the diagnosis and treatment of alopecia.

Objective Toinvestigatetheeffectofpressureandnon-pressureonthedirectimagingoflowerlimbdeepveinswith CTvenography(CTV).Methods 100patients(50malesand50females,aged30－80yearsold,mean (63.5±13.5yearsold)with suspectedlowerextremityvenousdiseasesfrom September2015to October2018 wereretrospectivelyanalyzed.50patientswere scannedafterpressingtheankle(controlgroup),andtheother50werescannedwithoutpressingtheankle(experimentalgroup).Results Therewerenosignificantdifferencesbetweenthecontrolandexperimentalgroupsintheauxiliaryveinscore (t＝－0.20,P＝0.82), femoralveinscore(t＝－0.1,P＝0.91),andtotaliliacveinscore(t＝－0.03,P＝0.97).Conclusion CTV withoutpressingtheankle demonstratescomparableefficacytodirectimagingoflowerlimbdeepveins,withgoodimagequality,reducedcomplicationsandeasy toapply,sothatitshouldbewidelyusedinclinicalpractice.