Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis / 中华医学杂志(英文版)

BACKGROUND@#Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.@*METHODS@#From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.@*RESULTS@#Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.@*CONCLUSIONS@#LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Two new C steroidal glycosides isolated from Cynanchum komarovii / 中国天然药物

The present study was designed to further investigate the C steroidal glycosides in Cynanchum plants. Two new steroidal glycosides based on a 13, 14:14, 15-disecopregnane-type aglycone, komaroside P (1) and komaroside Q (2), together with three known compounds (3-5) were isolated from the whole herbs of Cynanchum komarovii. The aglycones of compounds 1 and 2 were two new disecopregnane. Their structures were elucidated on the basis of 1D, 2D NMR spectroscopic data and acid hydrolysis. All the compounds (1-5) showed potent inhibitory activities against human leukemia cell lines (HL-60) with IC values ranging from 16.6 to 26.3 μmol·L, compared to the positive control 5-fluorouracil (6.4 μmol·L).

Two new C steroidal glycosides isolated from Cynanchum komarovii / 中国天然药物

The present study was designed to further investigate the C steroidal glycosides in Cynanchum plants. Two new steroidal glycosides based on a 13, 14:14, 15-disecopregnane-type aglycone, komaroside P (1) and komaroside Q (2), together with three known compounds (3-5) were isolated from the whole herbs of Cynanchum komarovii. The aglycones of compounds 1 and 2 were two new disecopregnane. Their structures were elucidated on the basis of 1D, 2D NMR spectroscopic data and acid hydrolysis. All the compounds (1-5) showed potent inhibitory activities against human leukemia cell lines (HL-60) with IC values ranging from 16.6 to 26.3 μmol·L, compared to the positive control 5-fluorouracil (6.4 μmol·L).

Anticancer Opportunity Created by Loss of Tumor Suppressor Genes.

Deletion of oncosuppressors occurs frequently in the cancer genome. A great deal of effort has been made to therapeutically restore the lost function of oncosuppressors, with little clinically translatable success, however. Reassuringly, besides the disappointing restoration endeavors, oncosuppressor loss can be therapeutically exploited in several other ways, such as the "synthetic lethality" strategies and the "therapeutic vulnerability" created by codeletion of neighboring genes. The study by Liu et al showed that codeletion of p53 and a neighboring essential gene POLR2A rendered colon cancer cells highly sensitive to further inhibition of POLR2A both in vitro and in vivo In recent years, several studies have reported similar phenomenon in a wide range of cancer types. In this focus article, we will introduce several kinds of anticancer opportunities created by the loss of oncosuppressors and discuss their mechanisms. Given the frequency of oncosuppressor loss in cancer, its therapeutic exploitation rather merits further investigation and may open a new window for oncotherapy.

LINE-1 in cancer: multifaceted functions and potential clinical implications.

Long interspersed nuclear element-1 (L1) retrotransposons are jumping genes that comprise 17% of human DNA. They utilize a ''copy-and-paste'' mechanism to propagate themselves throughout the genome via RNA intermediates, a process termed retrotransposition. L1s are active in the germ line and during embryogenesis, yet they are epigenetically suppressed in somatic cells. In cancer cells, however, L1s are aberrantly activated and may have a role in genome instability, one of the hallmarks of cancer pathogenesis. Their methylation states and retrotransposition activities are associated with and fluctuate during cancer initiation and progression, thus representing promising diagnostic biomarkers and therapeutic targets. During tumorigenesis, L1s exert both retrotransposition-dependent and retrotransposition-independent functions. The former may result in alterations in target gene expression or chromosomal rearrangement, or drive Alu and SVA, events that could function in tumorigenesis, whereas the latter can potentially exert epigenetic regulation by generating endo-siRNAs, forming chimeric L1 transcripts or changing the expression of adjacent genes by providing novel splicing sites or alternative promoters. Moreover, the L1 encoded proteins, ORF1p and ORF2p, may have pro-oncogenic potential by, for example, activating oncogenic transcriptional factors or sequestering oncosuppressors. Herein, we introduce the components and mechanisms of L1 retrotransposition, discuss the landscape, possible functions, and regulation of L1 activity in cancer, and seek their potential as diagnostic biomarkers and therapeutic targets.Genet Med 18 5, 431-439.

CRISPR-Cas9: a new and promising player in gene therapy.

First introduced into mammalian organisms in 2013, the RNA-guided genome editing tool CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) offers several advantages over conventional ones, such as simple-to-design, easy-to-use and multiplexing (capable of editing multiple genes simultaneously). Consequently, it has become a cost-effective and convenient tool for various genome editing purposes including gene therapy studies. In cell lines or animal models, CRISPR-Cas9 can be applied for therapeutic purposes in several ways. It can correct the causal mutations in monogenic disorders and thus rescue the disease phenotypes, which currently represents the most translatable field in CRISPR-Cas9-mediated gene therapy. CRISPR-Cas9 can also engineer pathogen genome such as HIV for therapeutic purposes, or induce protective or therapeutic mutations in host tissues. Moreover, CRISPR-Cas9 has shown potentials in cancer gene therapy such as deactivating oncogenic virus and inducing oncosuppressor expressions. Herein, we review the research on CRISPR-mediated gene therapy, discuss its advantages, limitations and possible solutions, and propose directions for future research, with an emphasis on the opportunities and challenges of CRISPR-Cas9 in cancer gene therapy.

Pseudogene in cancer: real functions and promising signature.

Pseudogenes were initially regarded as non-functional genomic fossils resulted from inactivating gene mutations during evolution. However, later studies revealed that they play a plethora of roles at multiple levels (DNA, RNA and/or protein) in diverse physiological and pathological processes, especially in cancer, both parental-gene-dependently and parental-gene-independently. Pseudogenes can interact with parental genes or other gene loci, leading to alteration in their sequences and/or transcriptional activities. Pseudogene-derived RNAs play multifaceted roles in post-transcriptional regulation as antisense RNAs, endogenous small-interference RNAs, competing endogenous RNAs and so on. Pseudogenic proteins can mirror, mimic or interfere with the functions of their parental counterparts. Herein, we discuss the general aspects (origination, classification, identification) of pseudogenes, focus on their multiple functions in cancer pathogenesis and prospect the potentials they hold as molecular signatures assisting in cancer reclassification and tailored therapy.

Correction of secondary lip whistle deformities and nasal base depression after bilateral cleft lip repair with lip subdermal soft tissue flap / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore a new method to correct secondary lip whistle deformities and nasal base depression after bilateral complete cleft lip (BCCL) repair with lip subdermal soft tissue flap.</p><p><b>METHODS</b>Bilateral subdermal soft tissue "C" flaps and "lambda" flap were designed to repair secondary deformities of nasal base and reconstruct vermilion tubercle in patients after BCCL repair.</p><p><b>RESULTS</b>Good results were achieved in all the patients with primary healing. No flap necrosis happened. The result was satisfactory.</p><p><b>CONCLUSIONS</b>With bilateral subdermal soft tissue "C" flaps and " lambda" flap, nasal base depression deformities and lip whistle deformities can be corrected. It is an ideal method for correction of deformities after BCCL repair.</p>

Preliminary study of in vitro chondrogenesis by co-culture of chondrocytes and adipose-derived stromal cells / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore the feasibility of in vitro chondrogenesis by co-culture of chondrocytes and adipose-derived stromal cells (ADSCs) so as to confirm the hypothesis that chondrocytes can provide chondrogenic microenvironment to induce chondrogenic differentiation of ADSCs.</p><p><b>METHODS</b>Human ADSCs and porcine auricular chondrocytes were in vitro expanded respectively and then were mixed at the ratio of 7:3 (ADSCs: chondrocytes). 200 microl mixed cells (5.0 x 10(7)/ml) were seeded onto a polyglycolic acid/polylactic acid (PGA/PLA) scaffold, 8 mm in diameter and 2 mm in thickness, as co-culture group. Chondrocytes and ADSCs with the same cell number were seeded respectively onto the scaffold as positive control group and negative control group. 200 microl chondrocytes (1.5 x 10(7)/ml) were seeded as low concentration chondrocyte group. There were 6 specimens in each group. All specimens were harvested after in vitro culture for 8 weeks in DMEM plus 10% FBS. Gross observation, histology, immunohistochemistry, wet weight measurement and glycosaminoglycan (GAG) quantification were used to evaluate the results. Multiple-sample t-test statistics analysis was done to compare the difference of wet weight and glycosaminoglycan(GAG) content between the groups.</p><p><b>RESULTS</b>Cells in all groups had fine adhesion to the scaffold and could secrete extracellular matrix. In co-culture group and positive control group, cell-scaffold constructs could maintain the original size and shape during in vitro culture. At 8 weeks, cartilage-like tissue formed in gross appearance and histological features, and abundant type II collagen could be detected by immunohistochemistry. Wet weight and glycosaminoglycan(GAG) content of co-culture group were respectively (174 +/- 12) mg and (7.6 +/- 0.4) mg. There were respectively 75% (P < 0.01) and 79% (P<0.01) of those of positive control group. In negative control group, however, constructs shrunk gradually without mature cartilage lacuna in histology. In low concentration chondrocyte group, constructs also shrunk obviously with small amount of cartilage formation at the edge area of the construct, and wet weight was (85 +/- 5) mg, which was 37% (P<0.01) of that of positive control group.</p><p><b>CONCLUSIONS</b>Chondrocytes can provide chondrogenic microenvironment to induce chondrogenic differentiation of ADSCs and thus promote the in vitro chondrogenesis of ADSCs.</p>

Endoscopic expand transnasal approach to the suprasellar region: anatomical study and clinical considerations / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The expanded endonasal approach (EEA) is used sparingly by surgeons for resection of lesions in the ventrocranial base. Herein, we examined the anatomy of the ventrocranial base by endoscopy and comment on the use of EEA in clinical practice.</p><p><b>METHODS</b>Twenty artery-injected adult cadaveric heads were studied under surgical conditions using the endoscopic EEA. The extent of the surgical exposure, the endoscopic anatomic view and the maneuverability of surgical instruments about the suprasellar region were studied by the endoscopic EEA.</p><p><b>RESULTS</b>The EEA by endoscope can reach the suprasellar region. In this approach, the optocarotid recess, supra and infra-optic chiasm interspace, the ophthalmic artery and others were important anatomical landmarks for identification of the suprasellar region.</p><p><b>CONCLUSIONS</b>The endoscopic EEA can be used to remove many types of lesions in the ventrocranial base. The microanatomy observed using the endoscope provides important anatomical information on the suprasellar region for neurosurgeons.</p>

Preliminary study on the phenomenon of epidermal stem cell ectopy in expanded skin / 中华烧伤杂志

<p><b>OBJECTIVE</b>To observe the differentiation and distribution of epidermal stem cell (ESC) after skin soft tissue expansion, and to initially probe into the growth mechanism of expanded skin tissue.</p><p><b>METHODS</b>Samples of normal skin and expanded skin (mean effusion period 45 days) were harvested from head and cervical region in 15 patients who underwent II stage surgery after skin expansion. Samples were divided into scalp adjacent to the center of expander group (expanded scalp, 3 cm from the vertical axis of the expander), scalp from lateral part of the expander group (expanded scalp, 5 - 7 cm lateral to the vertical axis of the expander), cervical skin expansion group, un-expanded scalp control group, and un-expanded cervical skin control group, according to the position of skin harvested. The tissue structure of skin in each group was observed with HE staining, and the differentiation and distribution characteristics of cytokeratin 19 (CK19) positive cells were observed with immunohistochemical staining.</p><p><b>RESULTS</b>Compared with those in the un-expanded control groups, uneven, relatively thickened and obviously folded epidermis with more cell layers and cells with obvious aggregation close to the basal layer were observed in the expanded groups, but those cells were not well-arranged and the transition of polarity was not obvious. The continuity of CK19 positive cells in the basal layer of skin was observed in each of the expanded group with immunohistochemical staining, and positive cells increased obviously and arranged in multilayer in certain parts of basal layer. Clustered or dispersed CK19 positive cells were also observed outside the basal layer. No above-mentioned phenomenon was observed in the un-expanded control group.</p><p><b>CONCLUSIONS</b>The proliferation and differentiation of ESC with ectopic distribution may enhance the repair process after skin soft tissue expansion.</p>

Violent head trauma in China: report of 2254 cases.

BACKGROUND: The occurrence of violent trauma has recently increased, and it has become both a social and medical problem in China. We are the first to explore violent head trauma in China. METHODS: Patients with violent head trauma were taken from all hospitalized patients with head trauma from January 2001 to December 2006 admitted to 11 hospitals in China. The rate, causes, age, sex, injury severity (GCS score), CT findings, management, outcome, and complications of patients with violent head trauma were retrospectively analyzed. RESULTS: Two thousand two hundred fifty-four (9.46%) patients with violent head trauma were found among a total of 23816 hospitalized patients with head trauma at 11 hospitals. Violent head trauma was caused by blunt objects (n = 1260, 55.90%), sharp/cutting instruments (n = 271, 12.02%), gunshots (n = 10, 0.44%), and others (n = 713, 31.63%). Violent head trauma was more likely to be found men (n = 1890, 83.85%) and in persons aged 21 to 40 years (n = 1216, 53.95%). In 2254 patients with violent head trauma, scalpel injury was seen in 1277 cases, skull fracture in 786 cases, cerebral contusion in 285 cases, and intracranial hematomas in 898 cases. Five hundred eighty-nine (26.13%) patients had body violent trauma besides violent head trauma. A GCS score of 13 to 15 was found in 1869 (82.92%) patients, 9 to 12 in 166 (7.36%), and 8 or less in 219 (9.72%). One thousand forty-two patients got surgical treatment, and another 1212 received medical management. One thousand nine hundred thirty-one (85.67%) patients had good recovery, 141 (6.47%) had moderate deficits, 36 (1.65%) had severe deficits, 7 (0.32%) had PVS, 63 (2.89%) died, and for the other 76, records were lost. CONCLUSIONS: Violent head trauma is certainly both a social and medical problem now, which indicates that violence should be controlled and that the human right of social safety needs to be improved in China.

Endoscopic endonasal transsphenoidal surgery in treatment of pituitary adenoma: Experience with 46 patients / 第二军医大学学报

Objective: To introduce our experience on endoscopic endonasal transsphenoidal surgery in 46 patients with pituitary adenomas. Methods: Forty-six patients (27 females and 19 males) with a median age of 39 years (range 22-73 years) were enrolled in this study. MRI or CT images showed that the diameters of the tumor were 3 cm in 8. Thirty-five patients had hormone-secreting adenomas and 11 had non-secreting ones. All patients received endoscopic endonasal transsphenoidal (absence of the transsphenoidal retractor) resection of the tumors and neuronavigation system was used in 3 cases. Results: Total tumor resection was achieved in 35 patients, subtotal in 6 and partial in 5. The operative time was from 1 to 3.5 hours. The postoperative hospitalization time was averagely 4.6 days (from 3 days to 10 days) and there was no operative death or optic nerve injury in our group. During follow-up (1 month to 3.3 years), 21 of the 23 patients with eyesight problems had their visual acuity improved and 24 of the 32 patients with abnormally high levels of hormones had their hormones restored to the normal levels. Two patients received γ-knife surgery after operation and 18 cases received radiation therapy 3 months after operation. Recurrence was found in 1 patient with MRI 1 year later and received neuronavigation-assisted endoscopic reoperation again. Conclusion: The method in this paper, with less operative trauma and complication, provides a satisfactory deep illumination and a panoramic operative field; moreover, it brings us more close to the operative target. All these factors contribute to the rapid recovery of patients.

Constructing Tissue Engineered Cartilage in Vitro Using a Perfusion-Hydrodynamic Pressure Bioreactor / 上海第二医科大学学报

Objective To explore the feasibility and efficacy of constructing tissue engineered cartilage in vitro(using) a perfusion-hydrodynamic pressure bioreactor. Methods Chondrocytes isolated from swine's auricular cartilage were seeded onto polyglycolic acid(PGA) to be cultured in a three dimensional environment for 1 week.Then the chondrocyte-polymer constructs were divided into two groups: the experimental group and control group(8 constructs in each group).The experimental group was put into the perfusion-hydrodynamic pressure bioreactor to be cultured for another 3 weeks.The parameters of bioreactor were set as follows: flow rate of 100 mL/min,clockwise and anticlockwise 30 min respectively,on/off 8 h/16h,hydrodynamic pressure of 100 kpa with 0.5 Hz for 4 h/d.The control group was cultured with the routine method.Specimens were harvested and analyzed by gross observation,histology,typeⅡcollagen immunohistochemistry and biochemistry after 4 weeks. Results After 4 weeks,gross observation showed cartilage-like tissue was formed in both groups,and tissue wet weight of experimental group and control group were(191.03?18.55) mg and(130.78?10.33) mg,respectively(P