Risk of thromboembolism in non-small-cell lung cancers patients with different oncogenic drivers, including ROS1, ALK, and EGFR mutations.

BACKGROUND: Anaplastic lymphoma kinase-positive (ALK+) and ROS proto-oncogene 1 (ROS1)-positive (ROS1+) lung cancers have been reported to be associated with an elevated risk of thromboembolic events. This study aimed to assess the long-term risk of developing thromboembolism (TE) in ROS1+ lung cancer and to compare it with other oncogenic drivers in the Asian population. MATERIALS AND METHODS: We retrospectively enrolled a cohort of ROS1+ lung adenocarcinoma in a medical center in Taiwan and a comparison cohort of ALK+ and epidermal growth factor receptor-positive (EGFR+) lung cancers. Venous and arterial TEs were identified throughout the cancer course, and the incidence rate was calculated. RESULTS: We enrolled 44 ROS1+, 98 ALK+, and 168 EGFR+ non-small-cell lung cancer (NSCLC) patients. A total of 11 (25%), 36 (36.7%), and 38 (22.6%) patients in the ROS1, ALK, and EGFR cohorts, respectively, were diagnosed with thromboembolic events throughout the follow-up course of the disease (P = 0.042). The incidence rates were 99.0, 91.9, and 82.5 events per 1000 person-years for the ROS1, ALK, and EGFR cohorts, respectively. The majority of thrombosis events in the ROS1 (91.6%) and ALK (85.4%) cohorts were venous. On the contrary, 43.2% of thromboembolic events were arterial in the EGFR cohort. A higher proportion of thromboembolic events were noted during cancer diagnosis in the ROS1 cohort (36.3%) than in the ALK (16.7%) and EGFR (10.5%) cohorts. The stage was the only clinical variable associated with thromboembolic risk. There was a significant difference in survival between patients with and without TE in the EGFR cohort, but not in the ALK and ROS1 cohorts. CONCLUSIONS: Although ROS1+ and ALK+ NSCLCs had a higher cumulative incidence of TE than EGFR+ NSCLC, the person-year incidence rates were similar among the three groups. EGFR-mutated NSCLC had more arterial events. Nevertheless, ALK+ lung cancer had higher venous events than EGFR-mutated lung cancer.

[Joint association of sedentary behavior and physical activity on anxiety tendency among occupational population in China].

OBJECTIVE: To investigate the status and influencing factors of anxiety tendency among occupational population in China and to examine the joint association between sedentary behavior and physical activity with anxiety tendency. METHODS: The data were from the 2021 Asia Best Workplace (Chinese mainland) program. The Generalized Anxiety Tendency scale was used to assess employees' anxiety status, and Logistic regression was used to analyze the factors influencing anxiety tendency and calculate the odds ratio (OR) within different groups. The OR of sitting for each sitting-physical activity (PA) combination group and within PA strata were calculated to explore the joint association. RESULTS: A total of 11 903 workers with an average age of 32.9 years were included in this study. Among them, 3 562 workers had anxiety tendency (29.9%) and the prevalence of those under 40 years old (30.6%) was significantly higher than the other age group (26.7%). 41.0% of the respondents had the moderated to vigorous physical activity. Their average daily sitting time was 9.4 h, and the percentage of those who exceeded 8 h sitting reached 73.9% in the past week. The analysis of Logistic regression showed that smoking (OR=1.24, 95%CI: 1.23-1.39), longer sedentary time and lower physical activity level were risk factors for anxiety tendency, and longer average daily sleep time (OR=0.56, 95%CI: 0.51-0.61) was a protective factor. The joint association analysis and stratified analysis of physical activity and sedentary behavior with anxiety tendency showed that increased sedentary time combined with decreased physical activity intensity was significantly associated with increased risk of anxiety tendency (range of OR: 1.64-3.14). The threshold for sedentary time in total as a risk factor for anxiety tendency gradually decreased as physical activity intensity increased. CONCLUSION: The anxiety tendency and sedentary behavior among the occupational population should recieve more attention. Lack of physical activity and sedentary behavior are both risk factors for anxiety tendency, and strengthening the intensity of physical activity can attenuate the harmful effects of sedentary behavior on anxiety tendency.

[Phenotypes and ATP7B gene variants in 316 children with Wilson disease].

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ2 test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 µg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) µg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.

[Incidence and mortality of corpus uteri cancer in China, 2015].

Objective: To estimate the incidence and mortality of corpus uteri cancer in China, 2015. Methods: Quality audit and evaluation of the data from 2015 cancer registration reported by 501 cancer registries were conducted, and 368 cancer registries were included in the analysis. The incidence rate and mortality rate of corpus uteri cancer were calculated according to the factors of the region (urban, rural, east, central, western), sex and age groups. The incidence and mortality of corpus uteri cancer with the 2015 population were estimated. Chinese standard population in 2000 and world Segi's population were used for the calculation of age-standardized rates (ASR) of incidence and mortality. Results: In 2015, 368 cancer registries included in the analysis covered a total of 309 553 499 populations in China, accounting for 22.52% of the national population. It is estimated that there were about 68 900 new cases of corpus uteri cancer in 2015, the incidence rate was 10.28/10(5), age-standardized incidence rates by Chinese standard population (ASR China) and world standard population (ASR world) were 6.86/10(5) and 6.66/10(5), respectively. The incidence rate of urban area (11.35/10(5)) was higher than that of rural area (8.90/10(5)), and the incidence of eastern region (12.12/10(5)) was higher than the central region (9.94/10(5)) and the western region (8.25/10(5)). It is estimated that in 2015, there were about 16 000 deaths of corpus uteri cancer, the mortality rate was 2.39/10(5), ASR China was 1.49/10(5), ASR world was 1.47/10(5). The mortality in urban areas (2.40/10(5)) is close to rural areas (2.39/10(5)); the mortality in central areas (2.55/10(5)) was higher than the eastern areas (2.32/10(5)) and the western areas (2.31/10(5)). Conclusions: In China, the incidence of corpus uteri cancer is on the rise and has a trend of youth, the burden of disease is gradually increasing, which threatens the health of women. Targeted prevention and control measures should be carried out in the different regions.

The Adverse Effects of Physical Restraint Use among Older Adult Patients Admitted to the Internal Medicine Wards: A Hospital-Based Retrospective Cohort Study.

OBJECTIVES: To evaluate the negative effect of physical restraint use on the hospital outcomes of older patients. DESIGN: A retrospective cohort study. SETTING: Internal medicine wards of a tertiary medical center in Taiwan. PARTICIPANTS: Subjects aged 65 years and over who were admitted during April to Dec 2017 were recruited for study. MEASUREMENTS: Demographic data, geriatric assessments (polypharmacy, visual impairment, hearing impairment, activities of daily living before and after admission, risk of pressure sores, change in consciousness level, mood condition, history of falls in the previous year, risk of malnutrition and pain) and hospital conditions (admission route, department of admission, length of hospital stay and mortality) were collected for analysis. RESULTS: Overall, 4,352 participants (mean age 78.7±8.7 years, 60.2% = male) were enrolled and 8.3% had physical restraint. Results of multivariate logistic regression showed that subjects with physical restraints were at greater risk of functional decline (adjusted odds ratio 2.136, 95% confidence interval 1.322-3.451, p=0.002), longer hospital stays (adjusted odds ratio 5.360, 95% confidence interval 3.627-7.923, p<0.001) and mortality (adjusted odds ratio 4.472, 95% confidence interval 2.794-7.160, p<0.001) after adjustment for covariates. CONCLUSION: The use of physical restraints during hospitalization increased the risk of adverse hospital outcomes, such as functional decline, longer length of hospital stay and mortality.

TNF-α Suppresses Autophagic Flux in Acinar Cells in IgG4-Related Sialadenitis.

IgG4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic fibroinflammatory disease that affects salivary glands and leads to hyposalivation. Tumor necrosis factor-α (TNF-α) is a critical proinflammatory cytokine involved in several salivary gland disorders, but its role and mechanism regarding acinar cell injury in IgG4-RS are unknown. Here, we found that TNF-α level was significantly increased in serum and submandibular gland (SMG) of patients and that serum TNF-α level was negatively correlated with saliva flow rate. Ultrastructural observations of IgG4-RS SMGs revealed accumulation of large autophagic vacuoles, as well as dense fibrous bundles, decreased secretory granules, widened intercellular spaces, swollen mitochondria, and expanded endoplasmic reticulum. Expression levels of LC3 and p62 were both increased in patients' SMGs. TNF-α treatment led to elevated levels of LC3II and p62 in both SMG-C6 cells and cultured human SMG tissues but did not further increase their levels when combined with bafilomycin A1 treatment. Moreover, transfection of Ad-mCherry-GFP-LC3B in SMG-C6 cells confirmed the suppression of autophagic flux after TNF-α treatment. Immunofluorescence imaging revealed that costaining of LC3 and the lysosomal marker LAMP2 was significantly decreased in patients, TNF-α-treated SMG-C6 cells, and cultured human SMGs, indicating a reduction in autophagosome-lysosome fusion. Furthermore, the ratio of pro/mature cathepsin D was elevated in vivo, ex vivo, and in vitro. TNF-α also appeared to induce abnormal acidification of lysosomes in acinar cells, as assessed by lysosomal pH and LysoTracker DND-26 fluorescence intensity. In addition, TNF-α treatment induced transcription factor EB (TFEB) redistribution in SMG-C6 cells, which was consistent with the changes observed in IgG4-RS patients. TNF-α increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, and inhibition of ERK1/2 by U0126 reversed TNF-α-induced TFEB redistribution, lysosomal dysfunction, and autophagic flux suppression. These findings suggest that TNF-α is a key cytokine related to acinar cell injury in IgG4-RS through ERK1/2-mediated autophagic flux suppression.

[The role of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving adjuvant chemotherapy].

Objectives: To investigate the efficacy and safety of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving docetaxel as adjuvant chemotherapy. Methods: A total of 58 patients with breast cancer receiving adjuvant chemotherapy with docetaxel were included between January 2014 to October 2017. Prophylactic use of PEG-rhG-CSF was administered.Patients were further divided into two groups according to the frequency of PEG-rhG-CSF use: frequent use group (≥3 cycles) and non-frequent use group (<3 cycles). Results: There were significant differences in the incidence rates of grade 3/4 neutropenia between the prophylactic group and non-prophylactic group in cycle 1-3(P<0.05). Less febrile neutropenia (FN) was also noted in the prophylactic group compared with the non-prophylactic group in cycle 1 and cycle 3 (P<0.05). Grade 3/4 neutropenia and FN were less in the frequent use of group compared with the non-frequent use group(P<0.001). The most common side effects of PEG-rhG-CSF included fatigue (10.2%), bone joint pain(50.8%), and 2 patients (3.4%) refused further treatment because of bone joint pain. Conclusions: PEG-rhG-CSF should be prophylactically used for preventing neutropenia and febrile neutropenia in breast cancer patients receiving adjuvant chemotherapy with docetaxel regimen.

[The effects of postauricular injection of methylprednisolone on medium-high frequency sudden hearing loss].

Objective:To study the effects of postauricular injection of methylprednisolone on medium-high frequency sudden hearing loss.Method:The data of 45 patients with invalid treatment who were diagnosed as medium-high frequency sudden hearing loss were retrospectively studied. They were divided into postauricular injection group and non-postauricular injection group. The treatment efficiency and hearing improvement at each frequency were compared between the two groups.Result:The improvements of hearing threshold in the non-postauricular injection group were(6.30±5.00)dB HL,(3.80±5.52)dB HL,(5.35±5.50)dB HL,(15.60±11.84)dB HL,(19.60±13.46)dB HL,(15.40±12.90)dB HL at 250, 500, 1000, 2000, 4000 and 8000Hz, respectively. The hearing improvements of the postauricular injection group were (5.35±6.22)dB HL,(2.50±3.00)dB HL,(4.65±6.60)dB HL,(23.75±10.75)dB HL,(25.75±11.73)dB HL,(30.50±14.50)dB HL at 250, 500,1000,2000,4000 and 8000Hz, respectively. There were significant differences between the two groups in hearing improvements at 2000-8000Hz. The treatment effective rates were 44% and 80% for the non-postauricular injection group and postauricular injection group respectively, which showed a significant difference(χ²=8.385P<0.05).Conclusion:Postauricular injection of methylprednisolone as a remedy treatment is safe and effective for sudden hearing loss in middle and high frequency.

Digital revascularization and replantation using the wide-awake hand surgery technique.

The use of local anaesthesia and adrenaline for hand surgery is gaining popularity; however, where vascularity is impaired, wide-awake surgery is considered a contraindication. We present our case series of five digital devascularizations and eight amputations that underwent surgery using the 'wide-awake' anaesthetic technique. A temporary digital tourniquet (< 20 min) was used in three cases to identify structures quickly. The anastomoses were performed under local anaesthesia without a tourniquet. All cases had successful re-establishment of blood flow with good perfusion to the digital tips; no cases were re-explored because of vascular crisis. Four cases had minor superficial soft tissue necrosis that healed secondarily. We conclude that digital revascularization and replantation can be performed under local anaesthesia with use of adrenaline and without detriment to the traumatized digit provided careful patient selection and adequate operator experience are available. LEVEL OF EVIDENCE: IV.

Endoscopy-assisted subfascial anterior transposition of the ulnar nerve for the treatment of cubital tunnel syndrome.

BACKGROUND: Many techniques have been described to relieve the compression and reduce subluxation of the ulnar nerve following surgery. The subfascial anterior transposition of the ulnar nerve (SfATUN) is one described technique, but involves a long scar, risk of injury to the medial antebrachial cutaneous nerve, and possible nerve ischemia from anterior transposition. We assessed a more refined approach of endoscopy-assisted SfATUN for the treatment of cubital tunnel syndrome. METHODS: A consecutive case series of 21 patients (15 males and 6 females) with evidence of nerve subluxation after ulnar nerve decompression were operated using an endoscopy-assisted SfATUN. Each patient was assessed with pre- and postoperative nerve conduction studies, McGowan grading, and recovery of grip strength. RESULTS: The average age of patients was 54 years (range 23-74 years), and they were followed up for a mean of 9 months (range 3-22 months). Preoperative McGowan grades were eight grade II and 13 grade III. Eighteen of the 21 patients showed improvement, including improvement by two McGowen grades in 8 patients and improvement by one grade in 10 patients. Three grade III patients did not show improvement in grading after surgery. A proportion of 90% of patients showed significant improvements in motor nerve conduction velocity of the ulnar nerve across the elbow (p < 0.001), and all showed some improvement in grip strength (p < 0.001). One patient underwent redo neurolysis. CONCLUSION: A combination of endoscopy-assisted SfATUN allows for decompression transposition and reduced strain on the ulnar nerve through a small scar. This is now our standard approach for cubital tunnel syndrome and the "unstable" nerve.

[Study on anti-oxidase in smoking-related laryngeal squamous cell carcinoma].

Objective:To investigate the role of oxidative stress in smoking-related laryngeal squamous carcinoma through detecting the expression of antioxidant enzymes in smoking patients. Method:A total of 138 cases with laryngeal squamous cell carcinoma enrolled in the first hospital affiliated the northern he bei college from 2012 to 2015 and forty five volunteers were conducted. All participants were divided into three groups according to smoking index: group A(heavy smoking, 88 cases of laryngeal cancer patients) and group B(no smoking 50 cases of laryngeal cancer patients) and C group(45 heavy smoking volunteers).Catalase(CAT), glutathione peroxidase(GSH-px) and malondialdehyde(MDA) and the expression of NRF2 in serum, tissue adjacent to carcinoma, and carcinoma tissues from each groups were measured, respectively. Result:①the expression of the CAT and GSH-px in group A were significantly lower than that of group B(P <0.05), but higher than that of group C(P <0.05); ②the MDA level of group A is significantly higher than group B(P <0.05) and C group(P <0.01);③NRF2 was highly expressed in carcinoma tissues, and the expression level was negatively correlated with degree of carcinoma differentiation (P <0.05). Conclusion:Compared with nonsmoking patients, heavy smoking patients with laryngeal cancer were under more severe oxidative stress. NRF2 expression level in patients with laryngeal squamous cell carcinomas was associated with pathological stage.

[Investigation of CXCR4 mediated chemoresistance in nasopharyngeal carcinoma cell line CNE2].

Objective:Since nasopharyngeal carcinoma is easy to develop resistance during cisplatin-based chemotherapy,CXCR4 expression levels were elevated in mang tumors,and the factor to do with tumor metastasis and chemotherapy drug resistance,and so on has a very important link.We established cisplatin-resistant nasopharyngeal carcinoma cell line, named as CNE2/DDP, and investigated the function of CXCR4 in molecular mechanism behind this resistance.Method:CNE2/DDP was firstly build up by increasing concentration of cisplatin. And then afterwards,MTT assay, RNA interference techniques, microRNA overexpresion techniques, quantative PCR and western blotting were applied to analyze the function of CXCR4 and its downstream effectors.Result:①the expression of CXCR4 was increased in CNE2/DDP and downregulation of CXCR4 with CXCR4 siRNA was able to decrease the resistance of CNE/DDP to cisplatin; ②the expression of let-7a was decrease in CNE2/DDP, while the expression of bcl-2 was increased. Upregulation of let-7a via transfection of let-7a mimics could downregulate the expression of bcl-2 and damage the resistance of CNE2/DDP to cisplation;③downregulation of CXCR4 through CXCR4 siRNA transfection was capable of improving the expression of let-7a. Conclusion:We were the first to found that CXCR4 was related to chemoresistance of CNE2/DPP to cisplatin. Meanwhile, we confirmed that CXCR4 affected the expression of bcl-2 through regulating the expression of let-7a to modulate the chemoresistance of CNE2/DPP to cisplatin.

Autoradiographic and histopathological studies of boric acid-mediated BNCT in hepatic VX2 tumor-bearing rabbits: Specific boron retention and damage in tumor and tumor vessels.

Hepatoma is a malignant tumor that responds poorly to conventional therapies. Boron neutron capture therapy (BNCT) may provide a better way for hepatoma therapy. In this research, (10)B-enriched boric acid (BA, 99% (10)B) was used as the boron drug. A multifocal hepatic VX2 tumor-bearing rabbit model was used to study the mechanisms of BA-mediated BNCT. Autoradiography demonstrated that BA was selectively targeted to tumors and tumor vessels. Histopathological examination revealed the radiation damage to tumor-bearing liver was concentrated in the tumor regions during BNCT treatment. The selective killing of tumor cells and the destruction of the blood vessels in tumor masses may be responsible for the success of BA-mediated BNCT for liver tumors.

miR-125a-5p expression is associated with the age of breast cancer patients.

Dysregulated miR-125 observed in multiple cancer types has suggested that it is involved in malignant proliferation and invasion. However, the clinical significance of miR-125 in human breast cancer (BC) has not yet been fully elucidated. In the present study, the expression of miR-125a-5p/3p and miR-125b in 143 pairs of BC and normal adjacent tissues (NATs) was measured by real-time quantitative PCR, and the correlation between expression and clinicopathological features was explored. miR-125a-5p and miR-125b were significantly down-regulated in BC tissue samples compared with their matched NAT samples, while the difference in miR-125a-3p expression between BC tissues and NATs was not statistically significant. The expression level of miR-125a-5p was found to be significantly higher in younger patients (<35 years) than in older patients (≥35, P = 0.005). When the patients were divided into three groups according to age (<35, 36-48, and ≥48 years), a gradual reduction in miR-125a-5p expression was observed in BC tissue samples that correlated to increases in age (P = 0.009). There were no significant correlations between miR-125 expression and other clinicopathological features including tumor size, histological grade, hormone receptor status, Her-2 status, and lymph node metastasis. Taken together, these findings suggest that miR-125a-5p may play an important role in BC progression in an age-dependent manner, and that the down-regulation of miR-125a-5p and miR-125b may serve as independent predictors for breast cancer.

Time-varying spectral analysis revealing differential effects of sevoflurane anaesthesia: non-rhythmic-to-rhythmic ratio.

BACKGROUND: Heart rate variability (HRV) may reflect various physiological dynamics. In particular, variation of R-R peak interval (RRI) of electrocardiography appears regularly oscillatory in deeper levels of anaesthesia and less regular in lighter levels of anaesthesia. We proposed a new index, non-rhythmic-to-rhythmic ratio (NRR), to quantify this feature and investigated its potential to estimate depth of anaesthesia. METHODS: Thirty-one female patients were enrolled in this prospective study. The oscillatory pattern transition of RRI was visualised by the time-varying power spectrum and quantified by NRR. The prediction of anaesthetic events, including skin incision, first reaction of motor movement during emergence period, loss of consciousness (LOC) and return of consciousness (ROC) by NRR were evaluated by serial prediction probability (PK ) analysis; the ability to predict the decrease of effect-site sevoflurane concentration was also evaluated. The results were compared with Bispectral Index (BIS). RESULTS: NRR well-predicted first reaction (PK > 0.90) 30 s ahead, earlier than BIS and significantly better than HRV indices. NRR well-correlated with sevoflurane concentration, although its correlation was inferior to BIS, while HRV indices had no such correlation. BIS indicated LOC and ROC best. CONCLUSIONS: Our findings suggest that NRR provides complementary information to BIS regarding the differential effects of anaesthetics on the brain, especially the subcortical motor activity.

Histopathological analysis and clinical correlation of drug reaction with eosinophilia and systemic symptoms (DRESS).

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse drug reaction. However, its histopathological features have not been well defined. OBJECTIVES: To identify the clinicohistopathological findings of DRESS, and analyse the cutaneous histopathological changes observed in DRESS compared with those observed in maculopapular exanthema (MPE). METHODS: In a retrospective study, conducted at Chang Gung Memorial Hospital (Taiwan) between 2001 and 2011, we compared the clinicohistopathological features of 32 patients with probable/definite DRESS (defined by the RegiSCAR scoring system) with those of 17 patients with MPE. RESULTS: The major pathological changes observed in patients with DRESS included dyskeratosis (97%), epidermal spongiosis (78%), interface vacuolization (91%), perivascular lymphocytic infiltration (97%) and eosinophilic infiltration (72%). Many pathological features were common to both MPE and DRESS. However, severe dyskeratosis, epidermal spongiosis and severe interface vacuolization were significantly more prominent in cases of DRESS (P < 0·05). The presence of severe dyskeratosis was significantly associated with the clinical severity of renal impairment (P = 0·01). CONCLUSIONS: The severe dyskeratosis detected in patients with DRESS may correlate with a greater extent of systemic involvement compared with that noted in MPE. However, the histopathological changes associated with DRESS are not entirely specific.

Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits.

OBJECTIVE: Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery. METHODS: EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation. RESULTS: At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-ß2 and TGF-ß3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th). CONCLUSION: The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors.

The physiology, microcirculation and clinical application of the shunt-restricted arterialized venous flaps for the reconstruction of digital defects.

Reconstruction of digital defects using the venous flap offer several advantages but remained unpopular owing to levels of venous congestion rates. We performed animal studies to test the hypothesis that an arterio-venous shunt increases pressure for peripheral flap perfusion and decreases venous congestion. Using an abdominal adipofascial flap model in six male Sprague-Dawley rats, microcirculation was modified as follows: type I - arterial flap; type II - flow-through arterio-venous flap (AVF); and type III - shunt-restricted AVF. In type I flaps, blood flow was observed to be unidirectional in both arterioles and venules. In type I flaps, blood flow was observed to be unidirectional in both arterioles and venules. In type II flaps, blood flow oscillated without a dominant direction and came to a standstill. In type III flaps, blood flowed proximally in a reverse direction whereas distally, flow was similar to type I flaps. In a clinical series, 21 patients received a total of 22 shunt-restricted AVFs. All 22 clinical flaps survived; four flaps suffered epidermolysis but recovered without full thickness loss.