HAI-1 is required for the novel role of FGFBP1 in maintenance of cell morphology and F-actin rearrangement in human keratinocytes.

Formation and maintenance of skin barrier function require tightly controlled membrane-associated proteolysis, in which the integral membrane Kunitz-type serine protease inhibitor, HAI-1, functions as the primary inhibitor of the membrane-associated serine proteases, matriptase and prostasin. Previously, HAI-1 loss in HaCaT human keratinocytes resulted in an expected increase in prostasin proteolysis but a paradoxical decrease in matriptase proteolysis. The paradoxical decrease in shed active matriptase is further investigated in this study with an unexpected discovery of novel functions of fibroblast growth factor-binding protein 1 (FGFBP1), which acts as an extracellular ligand that can rapidly elicit F-actin rearrangement and subsequently affect the morphology of human keratinocytes. This novel growth factor-like function is in stark contrast to the canonical activity of this protein through interactions with FGFs for its pathophysiological functions. This discovery began with the observation that HAI-1 KO HaCaT cells lose the characteristic cobblestone morphology of the parental cells and exhibit aberrant F-actin formation along with altered subcellular targeting of matriptase and HAI-2. The alterations in cell morphology and F-actin status caused by targeted HAI-1 deletion can be restored by treatment with conditioned medium from parental HaCaT cells, in which FGFBP1 was identified by tandem mass spectrometry. Recombinant FGFBP1 down to 1 ng/ml was able to revert the changes caused by HAI-1 loss. Our study reveals a novel function of FGFBP1 in the maintenance of keratinocyte morphology, which depends on HAI-1.

Three-target treatment combined with surgery for BRAF V600E-mutant colon cancer with peritoneal metastasis: a case report.

Background: BRAF V600E-mutant advanced colon cancer with peritoneal metastasis is associated with a poor prognosis. Surgery is not recommended by current guidelines, and there are few cases demonstrating the efficacy of targeted therapy combined with surgery in such patients. In the era of precision medicine, we apply aggressive surgery after successful conversion of triple-targeted drugs to prolong survival and provide a clinical basis for the treatment of such patients. Case Description: A 72-year-old male patient presented with abdominal distension and changes in bowel habits was admitted to the Department of Oncology, Shanxi Provincial People's Hospital. The patient was diagnosed with advanced ascending colon adenocarcinoma with peritoneal metastasis after relevant examinations such as abdominal enhanced computed tomography and tests of tumor markers. Later, further genetic testing was performed suggesting BRAF V600E mutation. We treated the patient with first-line three-target therapy (dabrafenib + trametinib + cetuximab). Repeat abdominal enhanced computed tomography after 6 weeks of three-target therapy revealed the disappearance of peritoneal metastases. Subsequently, after 3 months, the patient underwent resection of the primary lesion and removal of greater omental metastases. Three-target therapy continued after surgery until 4 months post-operation. However, carbohydrate antigen 199 was significantly increased at 9 months after medication discontinuation, and returned to normal after 4 months of re-initiation of three-target therapy. The three-target therapy was further adjusted to two-target therapy (dabrafenib + cetuximab) based on the results of circulating tumor cells, and the tumor markers are now normal. Conclusions: Patients with BRAF V600E colon cancer combined with peritoneal metastases are treated with targeted drug conversion therapy, and aggressive surgery may prolong survival depending on the conversion effect. Continued maintenance therapy after surgery may play a role in preventing recurrence.

Binary effects of intravascular laser irradiation of blood on motor recovery and homocysteine reduction in a case with ischemic hemiparesis: portrayed with brain perfusion images.

BACKGROUND: Stroke is a burdensome cerebral eventthat affects many aspects of daily activities such as motion, speech, memory, vision, and cognition. Intravascular laser irradiation of blood (ILIB) is a novel therapy, going beyond conventional rehabilitation modalities, that is effective in stroke recovery. Homocysteine ​​is an important risk factor associated with stroke. However, there are few studies that examine the relationship between ILIB treatment and the level of homocysteine. In recent years, researchers use the single-photon emission computed tomography (SPECT) scan of the brain to evaluate stroke patients and patients with a neurologicdeficit. The present report investigates the clinical effect of ILIB treatment on the level of serum homocysteine, the perfusion change of impaired brain region via SPECT, and the patient's neurologic appearance. CASEPRESENTATION: We focus on a case of a 62-year-old man with subacute stroke accompanied with left hemiparesis and hyperhomocysteinemia, who showed dramatic improvement in muscle power, a decreasing level of homocysteine, and increased blood flow of the right cerebral after three-courseILIB treatment. CONCLUSION: We found that ILIB is effective in lowering serum levels of homocysteine and facilitating cerebral circulation for the patient with subacute stroke.

The dominant strain of SARS-CoV-2 is a mosaicism.

COVID-19 is seriously threatening human health all over the world. A comprehensive understanding of the genetic mechanisms driving the rapid evolution of its pathogen (SARS-CoV-2) is the key to controlling this pandemic. In this study, by comparing the entire genome sequences of SARS-CoV-2 isolates from Asia, Europe and America, and analyzing their phylogenetic histories, we found a lineage derived from a recombination event that likely occurred before March 2020. More importantly, the recombinant offspring has become the dominant strain responsible for more than one-third of the global cases in the pandemic. These results indicated that the recombination might have played a key role in the pandemic of the virus.

Targeted deletion of HAI-1 increases prostasin proteolysis but decreases matriptase proteolysis in human keratinocytes.

Epidermal differentiation and barrier function require well-controlled matriptase and prostasin proteolysis, in which the Kunitz-type serine protease inhibitor HAI-1 represents the primary enzymatic inhibitor for both proteases. HAI-1, however, also functions as a chaperone-like protein necessary for normal matriptase synthesis and intracellular trafficking. Furthermore, other protease inhibitors, such as antithrombin and HAI-2, can also inhibit matriptase and prostasin in solution or in keratinocytes. It remains unclear, therefore, whether aberrant increases in matriptase and prostasin enzymatic activity would be the consequence of targeted deletion of HAI-1 and so subsequently contribute to the epidermal defects observed in HAI-1 knockout mice. The impact of HAI-1 deficiency on matriptase and prostasin proteolysis was, here, investigated in HaCaT human keratinocytes. Our results show that HAI-1 deficiency causes an increase in prostasin proteolysis via increased protein expression and zymogen activation. It remains unclear, however, whether HAI-1 deficiency increases "net" prostasin enzymatic activity because all of the activated prostasin was detected in complexes with HAI-2, suggesting that prostasin enzymatic activity is still under tight control in HAI-1-deficient keratinocytes. Matriptase proteolysis is, however, unexpectedly suppressed by HAI-1 deficiency, as manifested by decreases in zymogen activation, shedding of active matriptase, and matriptase-dependent prostasin zymogen activation. This suppressed proteolysis results mainly from the reduced ability of HAI-1-deficient HaCaT cells to activate matriptase and the rapid inhibition of nascent active matriptase by HAI-2 and other yet-to-be-identified protease inhibitors. Our study provides novel insights with opposite impacts by HAI-1 deficiency on matriptase versus prostasin proteolysis in keratinocytes.

[Transplantation of Autologous Peritoneum Using Ileal Seromuscular Flaps for Orthotopic Neobladder Reconstruction].

Objective To develop an ideal surgical procedure for neobladder reconstruction in experimental porcine models. Methods Six experimental female pigs weighting 28-33 kg underwent transplantation of autologous peritoneum for bladder reconstruction under general anesthesia.The flaps were used to reconstruct the orthotopic neobladder by suturing with the edges of the triangle and neck of the remnant bladder.The ureteral catheters were removed on the 5 th postoperative day and the balloon catheter was removed on the 7 th postoperative day.Voiding behaviour was monitored.The animals were euthanized at week 12 for routine pathology,immunohistochemistry,and electron microscopy. Results All the pigs survived after the surgery,and no postoperative complication such as peritonitis,intestinal obstruction,or urinary fistula was observed.All the peritoneum-ileum composite free valves survived after transplantation.Voiding behaviour was normal after catheter removal,and the urine was clear.At autopsy,reconstructed bladders were healthy.Pathological examination showed the neobladder had been covered by continuous urothelium while the peritoneum disappeared and showed no ileal mucosa regrowth and residual.Scanning electron microscope showed the transitional cells of neobladder were complete and orderly,and the urothelium around suture border was continuous and showed no malposition. Conclusions Reconstruction of bladder by autologous peritoneum and ileal seromuscular flaps is an ideal approach in the experimental pigs as it can prevent regrowth of ileal epithelial cells and avoid the complications of conventional enterocystoplasty.Its clinical application deserves further investigations.

SF36 Is a Reliable Patient-Oriented Outcome Evaluation Tool in Surgically Treated Degenerative Cervical Myelopathy Cases: A Systematic Review and Meta-Analysis.

BACKGROUND Degenerative spinal disorders have adverse impacts on patients' quality of life. Because the main objectives of any surgical intervention are to improve health-related quality of life and to reduce disability, instruments capable of measuring patient-oriented outcomes are now increasingly used. The aim of this study was to evaluate the use of the Short Form 36 Health Survey Questionnaire (SF36) for assessing patient-oriented outcomes of degenerative cervical myelopathy surgery. MATERIAL AND METHODS A literature search was conducted in electronic databases (Google Scholar, Ovid SP, PubMed, Science Direct, and Springer). Studies were included if they reported SF36 scores by following patients for at least 12 months. Random effects meta-analyses were performed to estimate changes in SF36 physical/mental component summary (SF36-PCS/MCS), SF36 dimensional, Japanese Orthopedics Association (JOA)/modified JOA (mJOA), and Neck Disability Index (NDI) scores by latest follow-up. RESULTS Fourteen studies (1966 patients; age 58.2 years [95% confidence interval (CI), 56.6 to 59.9]; 60% males [95% CI, 55 to 64]; follow-up 24.8 months [95% CI, 20.9 to 28.7]) were included in meta-analysis. SF36-PCS (6.60 [95% CI, 4.91 to 8.28]; p<0.00001), SF36-MCS (6.33 [95% CI, 4.31 to 8.35]; p<0.00001) and SF36 dimensional (p<0.05) scores improved significantly at latest follow-up. Surgery significantly improved JOA/mJOA (3.43 [95% CI, 2.80 to 4.06]; p<0.00001) and NDI (-13.70 [95% CI, -17.35 to -10.06]; p<0.00001) scores also. Change in SF36-PCS score were correlated (r=-0.554) with change in NDI score, whereas change in SF36-MCS score was correlated with change in JOA score (r=0.550). CONCLUSIONS Surgery for degenerative cervical myelopathy is associated with significantly improved SF36-measured patient-oriented outcomes.

The Correlation Production in Thermodynamics.

Macroscopic many-body systems always exhibit irreversible behaviors. However, in principle, the underlying microscopic dynamics of the many-body system, either the (quantum) von Neumann or (classical) Liouville equation, guarantees that the entropy of an isolated system does not change with time, which is quite confusing compared with the macroscopic irreversibility. We notice that indeed the macroscopic entropy increase in standard thermodynamics is associated with the correlation production inside the full ensemble state of the whole system. In open systems, the irreversible entropy production of the open system can be proved to be equivalent with the correlation production between the open system and its environment. During the free diffusion of an isolated ideal gas, the correlation between the spatial and momentum distributions is increasing monotonically, and it could well reproduce the entropy increase result in standard thermodynamics. In the presence of particle collisions, the single-particle distribution always approaches the Maxwell-Boltzmann distribution as its steady state, and its entropy increase indeed indicates the correlation production between the particles. In all these examples, the total entropy of the whole isolated system keeps constant, while the correlation production reproduces the irreversible entropy increase in the standard macroscopic thermodynamics. In this sense, the macroscopic irreversibility and the microscopic reversibility no longer contradict with each other.

Production rate of the system-bath mutual information.

When an open system comes into contact with several thermal baths, the entropy produced by the irreversible processes (dS_{i}=dS-∑_{α} dQ_{α}/T_{α}) keeps increasing, and this entropy production rate is always non-negative. However, when the system comes into contact with nonthermal baths containing quantum coherence or squeezing, this entropy production formula does not apply. In this paper, we study the increasing rate of mutual information between an open system and its environment. In the case of canonical thermal baths, we prove that this mutual information production rate could return exactly to the previous entropy production rate. Furthermore, we study an example of a single boson mode that comes into contact with multiple squeezed thermal baths, where the conventional entropy production rate does not apply, and we find that this mutual information production rate remains non-negative, which indicates a monotonic increase in the correlation between the system and its environment.

[Clinical study of application minimally invasive expandable channel in lumbar discectomy and interbody fusion and internal fixation].

OBJECTIVE: To explore the advantages of minimally invasive expandable in surgery of lumbar discectomy and interbody fusion and internal fixation. METHODS: The clinical data of 48 patients who underwent lumbar discectomy and interbody fusion and internal fixation from January 2010 to March 2016 was retrospectively analyzed. According to the admission queue, the patients were randomly assigned into channel group (26 cases) or traditional group (22 cases). In channel group, surgical approach of minimally invasive expandable channel was applied, and in traditional group, open posterior operation approach (including posterior lumbar interbody fusion and transforaminal lumbar interbody fusion, etc.) was applied. In channel group, there were 20 males and 6 females, aged from 43 to 74 years with an average of(56.6±5.1) years; course of disease was ranged from 4 to 22 months with an average of (6.7±1.8) months; 1 case was complicated with diabetes, 6 cases were complicated with hypertensive disease, and 2 cases were complicated with arrhythmia. In traditional group, there were 15 males and 7 females, aged from 43 to 73 years with an average of(55.9±4.6) years; course of disease was ranged from 4 to 26 months with an average of (6.2±2.1) months; 2 cases were complicated with diabetes, 5 cases were complicated with hypertensive disease, and 1 case was complicated with arrhythmia. Operation time, bleeding volume, and hospitalization time were compared between two groups and visual analogue scale(VAS), Oswestry Disability Index(ODI), bone fusion information, and complications correlated with incision were observed in two groups. RESULTS: All 48 patients were followed up for more than 6 months. Postoperative VAS and ODI were significantly improved (P<0.01), but 3 and 6 months after operation, there was no significant difference in VAS between two groups, and ODI score of channel group was lower than that of traditional group(P<0.01). Operation time, bleeding volume, hospitalization time in channel group respectively were (167.3±30.2) min, (786.8±147.8) ml, (12.3±2.4) d, and in traditional group were (197.5±48.7) min, (786.8±147.8) ml, (16.5±3.8) d, there was significant differences between two groups. There was no significant difference in fusion rate and fusion time between two groups. There were 4 cases and 7 cases developed incision related complications in channel group and traditional group, respectively. The difference between two groups was significant(P<0.01). CONCLUSIONS: Compared with conventional surgery minimally invasive lumbar discectomy and interbody fusion and internal fixation has advantages of less trauma, shorter operative time and better functional recovery.

Therapy and Prevention of Postoperative Urosepsis of Ureter Endoscopic Lithotripsy for Non-infection.

Objective To analyze the risk factors causing postoperative urosepsis in ureter endoscopic lithotripsy without infection preoperatively, in order to make a more effective and safer preventive and therapeutic strategy.Methods From January 2010 to January 2015, 5 ureteral calculus patients undergoing ureter endoscopic lithotripsy with holmium laser were retrospectively enrolled in this clinical study. These patients suffered urosepsis postoperatively confirmed by the clinical presentations and laboratory Results, while they had no infection in their blood and urine preoperatively. Without delay, 5 patients were treated by anti-inflammation and anti-shock.Results The vasopressor drug was stopped gradually after 12-36 hours. The body temperature was recovered to normal in 2 or 3 days, and the blood and urine test Results were not abnormal in 7 days. At last, 5 patients were all cured.Conclusions Stone and operation themselves are potential factors to cause urosepsis after ureter endoscopic lithotripsy. Especially for patients who had not presented infection preoperatively, careful preparation preoperatively, corrective manipulation, low pressure irrigation, drainage and controlling time during operation, and early diagnosis, appropriate treatment postoperatively are the key to cure and prevent urosepsis.

Photoelectric converters with quantum coherence.

Photon impingement is capable of liberating electrons in electronic devices and driving the electron flux from the lower chemical potential to higher chemical potential. Previous studies hinted that the thermodynamic efficiency of a nanosized photoelectric converter at maximum power is bounded by the Curzon-Ahlborn efficiency η_{CA}. In this study, we apply quantum effects to design a photoelectric converter based on a three-level quantum dot (QD) interacting with fermionic baths and photons. We show that, by adopting a pair of suitable degenerate states, quantum coherences induced by the couplings of QDs to sunlight and fermion baths can coexist steadily in nanoelectronic systems. Our analysis indicates that the efficiency at maximum power is no longer limited to η_{CA} through manipulation of carefully controlled quantum coherences.

Inhibition of presenilins attenuates proliferation and invasion in bladder cancer cells through multiple pathways.

OBJECTIVE: Presenilin (PS)/γ-secretase is a key protease that initiates various biological processes. We investigated the effect of PS/γ-secretase on the expression and inhibition of urothelial cell carcinoma of bladder (UCB) as a potential alternative therapeutic target for UCB. MATERIALS AND METHODS: PS-1 and PS-2 were identified in normal and malignant human bladder transitional cells by immunohistochemistry. We blocked PSs using a PS/γ-secretase inhibitor N-(N-[3,5-difluorophenacetyl]-L-alanyl)-S-phenylglycine-t-butylester (DAPT), and the proliferative and invasive potential of UCB cells SW780, BIU-87, 5637, and T24, and human normal urothelial cell line SV-HUC-1 were analyzed using Western blot, cell viability test, flow cytometry, and transwell assay. All experiments were repeated at least 3 times. RESULTS: Human bladder samples of UCB, SW780, BIU-87, 5637, and T24 cells expressed higher PS-1 compared with normal ones. Cell vitality test demonstrated that DAPT attenuated UCB cell proliferation more than SV-HUC-1. Flow cytometry and transwell assay showed that T24 cells were arrested at G1/S checkpoint and its invasive ability was impaired. Western blot assay markedly showed that protein levels of CD44-intracellular domain, insulinlike growth factor-1Rß, extracellular regulated protein kinase 1/2, cyclin D1, proliferating cell nuclear antigen, and matrix metalloproteinase-9 were downregulated by DAPT, whereas vascular endothelial growth factor receptor-2 and vascular endothelial growth factor-165 were upregulated. CONCLUSIONS: Our study revealed that PS-1 might be implicated in the proliferation and invasion of UCB, and that it may serve as a potential therapeutic target for UCB, but further studies are warranted to verify the effects of inhibition of PS/γ-secretase on angiogenesis.

Noncanonical statistics of a finite quantum system with non-negligible system-bath coupling.

The canonical statistics describes the statistical properties of an open system by assuming its coupling with the heat bath is infinitesimal in comparison with the total energy in thermodynamic limit. In this paper, we generally derive a noncanonical density matrix for the open system with a finite coupling to the heat bath, which deforms the energy shell to effectively modify the conventional canonical way. The obtained noncanonical distribution reflects the back action of system on the bath and thus depicts the statistical correlations between two subsystems by the mutual information as a result of energy conservation.

[Sigma rectum pouch for urinary diversion].

OBJECTIVE: To investigate the clinical outcome of sigma rectum pouch as a continent form of urinary diversion. METHODS: The clinical data of 38 patients, 32 males and 7 females, aged 53.2 (42 - 68) with muscle-invading bladder carcinoma who underwent a Mainz pouch II procedure after radical cystectomy 1996 - 2001 were analyzed. The intestine was incised over a length of 20 - 24 cm with the junction of sigmoid colon and rectum as the midpoint so as to create a low-pressure reservoir for urine and side-to-side anastomosis was performed on the posterior borders of the rectosigmoid wall. Submucosal tunnel technique was employed in antireflux urethral implantation. The patients were followed up for 7 - 60 months with a mean of 30 months postoperatively. RESULTS: Continence has been achieved in all the 38 patients with a micturition frequency of 3 - 5 times during daytime and 0 - 3 times at night. The mean volume of pouch was 515.6 ml (400 - 650 ml). The basal intra-reservoir pressure was 8 - 23 cm H(2)O (mean 16.5 cm H(2)O, 1 cm H(2)O = 0.098 kPa), the highest peak pressure was 12 - 33 cm H(2)O (mean 21.3 cm H(2)O). CONCLUSION: A modified sigmoid rectal pouch procedure provides a reservoir with a higher capacity and lower pressure without a reflux to the upper urinary tract and descending colon with lower incidence of complication, it is also a better alternative diversion procedure that would be easily accepted by surgeons and patients.

Mass screening of 12,027 elderly men for prostate carcinoma by measuring serum prostate specific antigen.

BACKGROUND: The incidence of prostate carcinoma (Pca) has been increasing in China. We detected Pca in elderly men in Changchun, north China and the significance of prostate specific antigen (PSA) in mass screening and clinical staging of Pca. METHODS: Serum PSA from 12,027 men over 50 years old from Changchun was analyzed. In case of serum PSA greater than 4.0 ng/ml, the patient was suspected of potentially suffering from Pca, and transrectal six-point puncture prostate biopsies were performed under ultrasound guidance. Pathological examinations were performed on the biopsy tissue, and ABCD and TNM clinical stagings were used in accordance with international standards. Correlations between serum PSA level and clinical stage were analyzed. RESULTS: PSA was greater than 4.0 ng/ml in 813 patients (6.8% of the 12,027 men). Transrectal six-point prostate puncture biopsies guided by ultrasound were performed in 273 patients (33.6% of the 813 patients who were tested positive in the initial mass screening). Of these 273 patients, 69 cases of Pca (25.3% of 273) were confirmed by biopsy in the second screening, with an overall detection rate for Pca of 0.57% (69/12,027). The total number of patients in stages A, B, T1, or T2 was 57.9%, and over 20% of them suffered from late stage Pca with lymph node and bone metastasis. An obvious positive correlation was observed between ABCD staging, TNM staging, and serum PSA level. CONCLUSIONS: Serum PSA level is not only the golden standard for mass screening of Pca, but also the predictor for clinical stage of Pca. PSA testing revealed asymptomatic Pca cases in early, middle, and later stages in the elderly, suggesting that mass screening is of paramount importance.

Preparation of controlled release microspheres of vascular endothelial growth factor & calcium alginate and their effects on proliferation of human umbilical vein endothelial cells / 中华创伤杂志

Objective To prepare controlled release microspheres of vascular endothelial growth factor(VEGF)& calcium alginate and observe their effect on proliferation of human umbilical vein endo- thelial cells(HUVEC)in order to provide theoretical basis for controlled release of VEGF facilitating an- giogenesis of tissue engineering bone.Methods VEGF-calcium alginate microspheres were prepared by using the needle extrusion/external gelation method to investigate physicochemical character and in vitro release of VEGF.According to the different ingredients added into the culture medium,the seconda- ry cultured HUVEC were divided into four groups,ie,control group,microsphere group,VEGF group and VEGF-calcium alginate microsphere group,in which the proliferation of the cultured HUVEC was ob- served with cell counting method,MTT method and flow cytometry.Results The calcium alginate mi- crospheres were revealed as spherical shape and evenly distributed,with mean grain diameter of(560?50)?m,carrying capacity of 0.72 ng/mg and the encapsulation efficiency of 54%.Smooth controlled re- lease in VEGF-alginate microspheres lasted for more than 10 days.Proliferation of the cultured HUVEC was accelerated the most in VEGF group at the beginning but in EGF-calcium alginate microsphere group at midanaphase compared with other groups,with statistical difference(P＜0.05).There was no statis- tical difference upon cell counting,cell activity and time point of cell cycle between control group and mi- crosphere group.Conclusion VEGF-sodium alginate microapheres can continue activity of VEGF,re- lease VEGF for over 10 days and promote proliferation cultured HUVEC for a long time.