Stabilization of labile active ingredients in an oil-water emulsion cosmetics by freeze-drying.

BACKGROUND: Due to the instability in oil/water emulsion, certain labile active ingredients were often not used in cosmetics. OBJECTIVE: The present study has tested the effect of freeze-drying to stabilize an oil/water cosmetic emulsion. MATERIALS AND METHODS: A preliminary freeze-drying process was established at the basis of calorimetric and freeze-drying microscope studies. The stability of labile molecules in the cosmetic emulsion was evaluated at 48 degree C after freeze-drying. RESULTS: The accelerated stability experiment showed that the freeze-dried emulsion retained 90.1% vitamin C after 28 days at 48 degree C, whereas the oil-water emulsion retained only 28.3% vitamin C. The freeze-dried emulsion had significantly less oil oxidation than did the oil-water emulsion. CONCLUSION: Freeze-drying improved the stability of vitamin C and oily active ingredients in cosmetic emulsions. DOI: 10.54680/fr23210110312.

Progressive plasticity during colorectal cancer metastasis.

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

[Analysis on the allocation of human resources for chronic disease prevention and control in 664 district/county-level centers for disease control and prevention in China in 2020].

Objective: To analyze the allocation of human resources for chronic disease prevention and control of district/county-level centers for disease control and prevention(CDC) in China in 2020. Methods: Survey subjects were from National Chronic Noncommunicable Disease and Risk Factor Surveillance Sites and National Demonstration Areas for Chronic Noncommunicable Disease Prevention and Control (demonstration areas). A survey examining the allocation of human resources for chronic disease prevention and control at district/county-level CDC was conducted in December 2021 through the National Demonstration Areas Management Information System. The number and rate of allocation of human resources for chronic disease prevention and control in district/county-level CDC were analyzed and the Wilcoxon rank sum test was used to compare the difference between demonstration and non-demonstration areas and between urban and rural areas. The Kruskal-Wallis H test was used to compare the difference in east, central and west regions. The Gini coefficient and Theil index were used to evaluate the balance of human resource for chronic disease prevention and control. Results: A total of 678 districts/counties were investigated, and 664 districts/counties responded effectively, with an effective response rate of 97.9%. The establishment rate of district/county-level CDC was 98.34% (653/664), and the establishment rate of chronic disease prevention and control departments of district/county-level CDC was 96.02% (627/653). In 627 district/county-level CDC with departments for chronic disease prevention and control, the median number of full-time technical personnel for chronic disease prevention and control was 4, the median number of full-time technical personnel in demonstration areas (4 persons) was higher than in non-demonstration areas (3 persons), highest in the east region (5 persons) than in the middle region (4 persons) and the west region (4 persons), higher in urban areas (4 persons) than in rural areas (4 persons) (all P values<0.05). The allocation rate was 0.71 people/100 000, which was higher in demonstration areas (0.73 people/100 000) than in non-demonstration areas (0.67 people/100 000), highest in the west region (0.82 people/100 000) than in the middle region (0.71 people/100 000) and east region (0.67 people/100 000), higher in rural areas (0.77 people/100 000) than in urban areas (0.68 people/100 000) (all P values<0.05). The Gini coefficient for the allocation by population size was 0.352 9. The total Theil index for demonstration and non-demonstration areas, different regions, and urban-rural areas were 0.067 8, 0.076 3, and 0.000 2, with the intra-group contribution of 97.35%, 99.52%, and 98.80%, respectively. Conclusion: In 2020, the allocation of human resources for chronic disease prevention and control in district/county-level CDC is relatively balanced. The variation in the allocation of human resources for chronic disease prevention and control exist between demonstration and non-demonstration areas, urban and rural areas, and across regions.

A comparison of low and high dose of moderate intensity aerobic exercise on heart rate recovery of the sedentary adults: a pragmatic randomized controlled trial.

BACKGROUND: Heart rate recovery (HRR) has been used as a prognostication marker of health. A slower drop in HRR is linked to a higher risk of cardiovascular diseases and all-cause mortality. Since aerobic exercise has been shown to have favorable effects on HRR, we aimed to compare the effects of two different aerobic exercise doses on HRR among a sedentary adult population. METHODS: A pragmatic randomised controlled trial was conducted on 29 healthy sedentary adults (seven males and 22 females) in a 12-week exercise program. They were randomly assigned to group A (75 min/week, N.=15) or group B (150 min/week, N.=14) of moderate intensity aerobic exercise groups. HRR at 1-minute (HRR1), HRR at 2-minute (HRR2), and peak oxygen uptake (VO2peak) were measured pre- and post-intervention. RESULTS: The improvements of HRR1 and HRR2 were seen in both groups but was only significant (P<0.05) for group A with HRR1, -4.07 bpm (post 24.47±6.42 - pre 20.40±5.51, P=0.018) and HHR2, -3.93 bpm (post 43.40±13.61 - pre 39.47±10.68, P=0.046). Group B showed increment of HRR1, -1.14 bpm (post 21.14±5.35 - pre 20.00±6.30, P=0.286) and HRR2, -2.5 bpm, (post 39.36±8.01 - pre 36.86±9.57, P=0.221). Improvement of the VO2peak was only significant in group B with an increment of 1.52±2.61 (P=0.049). CONCLUSIONS: In conclusion, our study suggests that improvements in heart rate recovery (HRR1 and HRR2) among sedentary healthy adults can be achieved by engaging in moderate intensity exercise at a dose lower than the current recommended guidelines. The lower dose seems to be more attainable and may encourage exercise compliance. Future studies should further explore the effects of different exercise volumes on HRR in a larger sample size and also by controlling for BMI or gender.

[Transplantation of bilateral superficial inferior epigastric artery perforator flap for breast reconstruction in a patient with unilateral breast cancer].

On May 14, 2020, a 37 year old female patient with unilateral breast cancer was admitted to Hunan Cancer Hospital. She underwent modified radical mastectomy for right breast cancer and free transplantation of bilateral superficial inferior epigastric artery perforator flap (weighed 305 g) for breast reconstruction. During the operation, the right inferior epigastric vascular pedicle was anastomosed with the proximal end of the right internal mammary vessel, and the left inferior epigastric vascular pedicle was anastomosed with the distal end of the right internal mammary vessel; the blood flow of the flap was good; the wound in the donor site of the abdominal flap was closed directly. The operation lasted for 9 hours. In the first 48 hours post operation, the flap showed mild elevation in perfusion over drainage, but no obvious edema or blister was observed, flap temperature was consistent with the surrounding skin, and the drainage volume out of drainage tube was only 40 mL. The blood supply of the flap was completely restored to normal 3 days post operation, the flap survived well, the donor site incision had no obvious tension, and the healing was smooth. After 2 months of follow-up, the donor site incision of abdomen healed completely, only linear scar was left, and the reconstructed breast had a natural appearance; the patient planned to perform further nipple reconstruction and contralateral breast mastopexy. This case suggests that autologous breast reconstruction can be performed using bilateral superficial inferior epigastric artery perforator flaps under certain circumstances to minimize donor site injury to the greatest extent.

Changes in macular vascular density and retinal thickness in young myopic adults without pathological changes: an OCTA study.

OBJECTIVE: The aim of the study was to quantify the macular vascular density and retinal thickness in the eyes of young myopic people with myopia without pathological changes using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: In this cross-sectional study, 160 eyes of 80 myopia subjects without pathological changes were classified into three groups: mild myopia (N=40 eyes), moderate myopia (N=66 eyes), and high myopia (N=54 eyes). Macular vascular density (VD), retinal thickness, area of the foveal avascular zone, the flow area of the outer retina and choriocapillaris (CC) were measured using OCTA. The effects of other confounding factors including axial length, the spherical equivalent, and some systemic factors (blood pressure, height, weight, etc.) were also considered. RESULTS: As the severity of myopia increases, the CC flow area decreased (p=0.029). The superficial VD in the temporal, superior, nasal, and inferior regions was significantly lower in high myopia group compared to moderate and low myopia groups (all p<0.001). With increasing myopia, a significant reduction of deep VD was found in the superior region of the macula (p=0.007). In the fovea, there was no difference in the superficial or deep VD across groups (p=0.268 and p=0.413, respectively). Parafoveal retinal thickness was thinnest in the high myopia group and thickest in the mild myopia group (all p<0.05). The fovea was thickest in the high myopia group and thinnest in the mild myopia group (p=0.030). CONCLUSIONS: In young myopic people without pathological changes, superficial VD and retinal thickness decreased with myopia progression, except in the fovea. The CC flow area decreased with increasing myopia.

A Therapeutic Journey of Potential Drugs Against COVID-19.

Coronavirus disease (CoVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) scrambles the world by infecting millions of peoples all over the globe. It has caused tremendous morbidity, mortality and greatly impacted the lives and economy worldwide as an outcome of mandatory quarantines or isolations. Despite the worsening trends of COVID-19, no drugs are validated to have significant efficacy in the clinical treatment of COVID-19 patients in large-scale studies. Physicians and researchers throughout the world are working to understand the pathophysiology to expose the conceivable handling regimens and to determine the effective vaccines and/or therapeutic agents. Some of them re-purposed drugs for clinical trials which were primarily known to be effective against the RNA viruses including MERS-CoV and SARS-CoV-1. In the absence of a proven efficacy therapy, the current management use therapies based on antivirals, anti-inflammatory drugs, convalescent plasma, anti-parasitic agents in both oral and parenteral formulation, oxygen therapy, and heparin support. What is needed at this hour, however, is a definitive drug therapy or vaccine. Different countries are rushing to find this, and various trials are already underway. We aimed to summarize the potential therapeutic strategies as treatment options for COVID-19 that could be helpful to stop further spread of SARS-CoV-2 by affecting its structural components or modulation of immune response and discuss the leading drugs/vaccines, which are considered as potential agents for controlling this pandemic.

Spatiotemporal changes of CT manifestations in 110 patients with COVID-19 pneumonia.

OBJECTIVE: The aim of the study was to analyze spatiotemporal changes of CT manifestations in patients with COVID-19 pneumonia. PATIENTS AND METHODS: In this retrospective review, 110 patients with confirmed COVID-19 by RT-PCR form February 16, 2020, to March 28, 2020 were included. A total of 449 CT scans were reviewed. We analyze the type and distribution of lung abnormalities, and CT general assessment and lesion area statistics were performed. Patients were divided into mild, moderate, and severe disease based on Chinese guidelines: mild (patients with minimal symptoms, CT scans showed no pneumonia or a small area of pneumonia infection), moderate (different extent of clinical manifestations and CT scans showed multiple pneumonia infections in both lungs), severe disease (respiratory distress, CT scans lesion area exceeds 50%, and the lesion contains consolidation). The proportion of patients with mild, moderate and severe diseases was counted. RESULTS: The CT score and the area involved reached a peak (median 10) on illness days 7-12, and then, continued to be at a high level. The main abnormal pattern after symptoms appeared GGO (36/94 [36%] to 40/65 [62%] in different periods). The proportion of mixed reached its peak on illness days 13-18 (36/93 [39%]). Pure GGO was the most common subtype of GGO (24 of 60 CT scans [40%] to 23 of 33 CT scans [70%]) after symptoms onset. The ratio of GGO with irregular lines and interfaces peaked on illness days 7-12 (6/34 [18%]). The lesions are mainly distributed on both sides and under the pleura. 76/84 (90%) of discharged patients had residual lesions on the final CT scans. 4 confirmed patients' CT scans did not show lesions (on illness days 1-24 days). There were 47 mild cases (42.7%), 46 moderate cases (41.8%), and 7 severe cases (6.3%). CONCLUSIONS: The degree of lung abnormality on the CT of the patients reached the peak on the 7th to 12th days of the disease. CT performance changes with time have a certain regularity, which may indicate the progress and recovery of the disease. 90% of patients still observed residual lung abnormalities in CT images at the time of discharge. There were 4 confirmed cases where the CT images did not show the lesion; hence, CT cannot be used as a basis for judging COVID-19 as a single tool.

[Exploration of the high-risk factors of catheter-related thrombosis in breast cancer].

Objective: To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies. Methods: A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed. Results: The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old (OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC (OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein (OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position (OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level (OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions: The CRT problem can't be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

The PKM2 activator TEPP-46 attenuates MCD feeding-induced nonalcoholic steatohepatitis by inhibiting the activation of Kupffer cells.

OBJECTIVE: The present study aimed to investigate the effect and molecular mechanism of the PKM2 small molecule agonist TEPP-46 on the development of methionine choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH) in mice. MATERIALS AND METHODS: In this study, C57BL/6 mice were fed an MCD diet for 15 days to establish a NASH model. The protein expression levels of pyruvate kinase M2 (PKM2), PKM1, hypoxia-inducible factor-1α (HIF-1α) and NLRP3 in liver Kupffer cells (KCs) were measured by Western blotting. Immunofluorescence analysis was used to analyze the nuclear translocation of PKM2 in KCs, and the levels of IL-1ß and TNF-α in mouse serum and the cell polarization indexes were determined. The MCD diet-fed mice were injected with 30 mg/kg of TEPP-46 intraperitoneally every 5 days. After 15 days, the liver tissue and peripheral blood were collected for analysis. RESULTS: We found the NASH model was successfully established after the mice were fed an MCD diet for 15 days. MCD feeding promoted the expression of the PKM2 monomer/dimer and inhibited the expression of the PKM2 tetramer in KCs. Immunofluorescence analysis further confirmed that MCD feeding inhibited the nuclear translocation of PKM2. Besides, MCD feeding promoted the expression of HIF-1α and NLRP3 in KCs, promoted M1 KCs polarization and inhibited M2 KCs polarization. Intraperitoneal injection 30 mg/kg of TEPP-46 significantly inhibited the development of MCD diet-induced NASH, alleviated the pathological changes in the liver, improved liver function, promoted the expression of the PKM2 tetramer in KCs, and inhibited the expression of HIF-1α and NLRP3. CONCLUSIONS: This study demonstrated that TEPP-46, a small molecule agonist of PKM2, may inhibit the nuclear translocation of PKM2 and the activation of KCs by promoting the expression of PKM2 tetramers in KCs, thus inhibiting the development of MCD diet-induced NASH in mice.

[Evaluation of intravascular therapy for cerebral ischemic tandem stenosis].

Objective: To investigate the efficacy and the safety of intravascular therapy for cerebrovascular ischemic tandem stenosis. Methods: Clinical data of 35 patients with symptomatic anterior circulation and posterior circulation tandem stenosis who received intravascular therapy for two sites of stenosis at the same time at Department of Neurosurgery of Peking University First Hospital from January 2013 to December 2018 were analyzed retrospectively. There were 27 males and 8 females,aged (65.6±9.4)years (range:47 to 81 years).There were 14 cases of anterior circulation tandem stenosis and 21 of posterior circulation tandem stenosis.The medical records were collected with emphasis on postoperative symptoms,imaging manifestations and modified Rankin scale(mRS) scores. Results: Sixty-eight stents were implants in to 35 patients,including 49 extracranial implants and 19 intracranial implants.The surgical success rate was 100%.The perioperative death rate was 0,and 1 patient(1/35,2.9%) had cerebral hemorrhage.All patients were followed up for 18 months.During 3 to 12 months after the intervention,1 case(1/35,2.9%) had stent restenosis,and 4 cases(4/35,11.4%) had persisted symptoms such as dizziness and weakness in limbs.All patients'mRS scores were ≤2. No new stroke occurred. During 12 to 18 months after the intervention,3 cases had in-stent restenosis,increasing the rate to 11.4% (4/35). The mRS scores of 32 patients(32/35,91.4%) were ≤2. Conclusion: Intravascular therapy for patients with symptomatic tandem stenosis is a feasible and safe procedure with good short-term outcomes.

[Evaluation of the single stage treatment of intracranial or extracranial artery stenosis combined with intracranial aneurysm:experience from a single center].

Objective: To investigate the strategy and the clinical effect of single stage treatment for intracranial or extracranial artery stenosis with intracranial aneurysm. Methods: The clinical data of 15 patients with intracranial aneurysms and extracranial or intracranial artery stenosis treated by one-stage endovascular therapy at Department of Neurosurgery of Peking University First Hospital from April 2013 to September 2018 were analyzed,respectively.There were 6 males and 9 females,aged (63.9±9.1)years (range:43 to 79 years).Fifteen arterial stenosis were found, including 8 in anterior circulatiion and 7 in posterior circulation, and the stenosis rates ranged from 75% to 95%. There were 17 aneurysms, among which 11 in the anterior circulation and 6 in the posterior.The maximal diameter was (5.3±1.2)mm (range:3 to 7 mm).All patients were treated with stenting and embolization at one stage. The operation choices, perioperative and postoperative symptoms,imaging data and complications were recorded. Results: Stents were successfully implanted into arterial stenosis of 15 cases, reducing the stenosis rates to less than 30%.Among the 17 aneurysms,10 cases were treated by coil embolization alone,7 cases by stenting and coil embolization. Eventually all the 17 aneurysms reached complete embolization.One patient had mild symptoms of the cerebral infarction during the perioperative period,and the rest had not shown surgical complications.The follow-up time was (43.8±8.2)months (range:24 to 85 months). All the patients underwent digital subtraction angiography 6 to 12 months after operation.Among them,2 cases had asymptomatic in-stent restenosis,and no recurrence was found in aneurysms.Up to the last follow-up,no patients had showed new symptoms or signs of intracranial hemorrhage or ischemic stroke. Conclusions: For patients suffered from both stenosis and aneurysms,individualized treatment should be made based on the location and severity of the vascular stenosis and aneurysms.With careful preoperative evaluation and surgical planning,the single stage endovascular treatment for intracranial or extracranial artery stenosis combined with intracranial aneurysm is safe,feasible and effective for selected patients.

Recurrent ZNF83-E293V Mutation Promotes Bladder Cancer Progression through the NF-κB Pathway via Transcriptional Dysregulation of S100A8.

Urothelial carcinoma (UC) is the predominant form of bladder cancer. Significant molecular heterogeneity caused by diverse molecular alterations brings about large variations in the response to treatment in UC. An improved understanding of the genetic mechanisms underlying the development and progression of UC is essential. Through deep analysis of next-generation sequencing data of 99 UC patients, we found that 18% of cases had recurrent somatic mutations in zinc finger protein gene zinc finger protein 83 (ZNF83). ZNF83 mutations were correlated with poor prognosis of UC. We also found a hotspot mutation, p.E293V, in the evolutionarily well-conserved region of ZNF83. ZNF83-E293V increased tumor growth and reduced the apoptosis of UC cells compared to wild-type ZNF83 both in vitro and in mice xenografted tumors. ZNF83-E293V activated nuclear factor κB (NF-κB) more potently than did the wild-type protein owing to its decreased transcriptional repression for S100A8. The NF-κB inhibitors could pharmacologically block the tumor growth in mice engrafted with ZNF83-E293V-transfected UC cells. These findings provide a mechanistic insight and a potential therapeutic strategy for UC, which established a foundation for using the ZNF83-E293V mutation as a predictive biomarker of therapeutic response from NF-κB inhibitors.

[Exploration on endovascular treatment for symptomatic occlusion of the intracranial vertebral arteries in early non-acute stage].

Objective: To examine the clinical efficacy of endovascular treatment on symptomatic occlusion of intracranial vertebral artery (ICVA) in early non-acute stage. Methods: Nine consecutive patients who presented with aggressive ischemic events in the early non-acute stage of ICVA occlusion from January 2014 to December 2019 and received endovascular treatment at Department of Neurosurgery, Peking University First Hospital were retrospectively reviewed.There were 7 males and 2 females, aged 63.4 years old(range: 52 to 72 years).The average preoperative modified Rankin scale(mRS) was 4.3(range: 4 to 5), the National Institute of Health stroke scale(NIHSS) was 12.3(range: 8 to 18). Among them, 2 patients received a single stage endovascular treatment, and the other 7 patients received staged endovascular treatment.The strategy of staged treatment was as follows: firstly, the occlusion part was passed through by a micro-guidewire and dilated with balloons to maintain the blood flow above Thrombolysis In Cerebral Infarction grade 2b. Then, the intravascular large load thrombus was eliminated by the fibrinolytic system and strengthened antiplatelet drugs. After that, a second stage of angioplasty with stenting was performed on the severe residual stenosis part.The complications and the recanalization rate were collected, and the National NIHSS and mRS after endovascular treatment and in follow-up period were recorded. Results: In the 2 cases received single stage endovascular treatment, although revascularization was achieved lastly, one patient suffered embolus translocation and the other suffered re-occlusion after mechanical thrombectomy during the operation, respectively.Technical success was achieved in 6 of the 7 patients received staged endovascular treatment.On discharge, the average NIHSS scores was 5.7(range: 3 to 4) of the patients. Three months after operation,the average mRS was 1.6(range:0 to 3) and it was 0.9(range: 0 to 2) at the latest follow-up, which were better than preoperative status. Conclusions: Staged endovascular treatment might be a safe, efficient, viable option in carefully selected patients with symptomatic ICVA occlusion in early non-acute stage. It needs to be confirmed by further investigation, preferably in a large controlled setting.

Activation of p38MAPK in spinal microglia contributes to autologous nucleus pulposus-induced mechanical hyperalgesia in a modified rat model of lumbar disk herniation.

Recent studies have implicated the activation of p38 mitogen-activated protein kinase (MAPK) and glial cells contribute to hyperalgesia following nerve injury or nerve compression. In our work, we investigated the underlying mechanisms of autologous nucleus pulposus (NP)-induced mechanical hyperalgesia in a modified rat model of lumbar disk herniation (LDH). Firstly, our results showed that 50% mechanical withdrawal threshold (50% MWT) decreased on postoperative day (POD) 1 and significantly minimally reduced on POD 7 and lasted for day 28 after surgery (P < 0.05). Secondly, phosphorylation of p38MAPK (p-p38MAPK) and glial cells were monitored on POD 1, 3, 7, 14 and 28 using immunofluorescence staining. P38MAPK activation, observed in the spinal cord, began to increase on POD 1, peaked on POD 3, and significantly decreased on POD 14 and POD 28 (P < 0.05). Microglia activation was initiated at day 1, maximal at day 3, and maintained until day 14 after surgery (P < 0.05). Astrocytic activation was found in 7 to 14 days after modelling (P < 0.05). Then, double immunostaining method was applied to observe the co-expression of p-p38MAPK and glial cells, and it showed that p-p38MAPK was mainly expressed in activated microglia, rarely in neurons, and none in astrocytes. Lastly, we discovered that both SB203580 (50ug, p38MAPK inhibitor) and minocycline (0.5 mg, microglial inhibitor) would inhibit the p-p38MAPK protein expression tested by western blot analysis and reduce mechanical hyperalgesia. In conclusion, current study suggest that activation or phosphorylation of p38MAPK in spinal microglia contributes to autologous NP-induced mechanical hyperalgesia in our animal model.

Clinical and economic burden of wound care in the tropics: a 5-year institutional population health review.

The aim of this study is to evaluate the clinical and economic burden of wound care in the Tropics via a 5-year institutional population health review. Within our data analysis, wounds are broadly classified into neuro-ischaemic ulcers (NIUs), venous leg ulcers (VLUs), pressure injuries (PIs), and surgical site infections (SSIs). Between 2013 and 2017, there were a total of 56 583 wound-related inpatient admissions for 41 461 patients, with a 95.1% increase in wound episodes per 1000 inpatient admissions over this period (142 and 277 wound episodes per 1000 inpatient admissions in 2013 and 2017, respectively). In 2017, the average length of stay for each wound episode was 17.7 days, which was 2.4 times that of an average acute admission at our institution. The average gross charge per wound episode was USD $12 967. Among the 12 218 patients with 16 674 wound episodes in 2017, 71.5% were more than 65 years of age with an average Charlson Comorbidity Index (CCI) of 7.2. Half (51.9%) were moderately or severely frail, while 41.3% had two or more wound-related admission episodes. In 2017, within our healthcare cluster, the gross healthcare costs for all inpatient wound episodes stand at USD $216 million within hospital care and USD $596 000 within primary care. Most NIU patients (97.2%) had diabetes and they had the most comorbidities (average CCI 8.4) and were the frailest group of patients (44.9% severely frail). The majority of the VLU disease burden was at the specialist outpatient setting, with the average 1-year VLU recurrence rate at 52.5% and median time between healing and recurrence at 9.5 months. PI patients were the oldest (86.5% more than 65 years-old), constituted the largest cohort of patients with 3874 patients at an incidence of 64.6 per 1000 admissions in 2017, and have a 1-year all-cause mortality rate of 14.3%. For SSI patients, there was a 125% increase of 14.2 SSI wound episodes per 1000 inpatient admissions in 2013 to 32.0 in 2017, and a 413% increase in wound-related 30-day re-admissions, from 40 in 2013 (4.1% of all surgeries) to 205 (8.3% of all surgeries) in 2017. The estimated gross healthcare cost per patient ranges from USD $15789-17 761 across the wound categories. Similar to global data, there is a significant and rising trend in the clinical and economic burden of wound care in Tropics.

Research on function and mechanisms of a novel small molecule WG449E for hypertrophic scar.

BACKGROUND: Hypertrophic scars are complications of severe wound healing characterized by excessive fibrosis associated with aberrant function of fibroblasts. However, no available drugs can be utilized to effectively treat these scars. The transforming growth factor ß (TGFß) signalling pathway regulates collagen synthesis and plays an important role in scar formation. OBJECTIVES: To evaluate the anti-scar effects of TGFß inhibitors in vitro and in vivo. METHODS: Col1α2-luciferase reporter assay was used to screen the compounds suppress type I collagen gene transcription. Sulforhodamine B colorimetric assay and colony formation assay were used to test the compound's effect on cell proliferation. Wound healing and transwell assay were performed to test the cell migration and invasion. Western blotting, immunofluorescence, immunohistochemistry and Q-PCR assay were used to determine the protein and mRNA levels. 3D cell contraction assay was used to examine the cell contraction. Flow cytometry was performed to analyse cell apoptosis. Masson stain, H&E stain and immunochemistry were used to analyse the scar formation in vivo. RESULTS: WG449E, as one of the most potent inhibitors, was identified to significantly downregulate the mRNA and protein levels of collagen in hypertrophic scar-derived fibroblasts through inhibiting Smad2/3 phosphorylation. WG449E inhibited the proliferation, migration and contraction of fibroblasts in vitro and in vivo. In addition, WG449E induced cell apoptosis through the activation of cleaved-caspase3. Moreover, WG449E significantly attenuated hypertrophic scar formation and collagen deposition in a mechanical load-induced mouse model. CONCLUSIONS: WG449E is a potential candidate for the treatment of hypertrophic scars.WG449E downregulates the mRNA and protein levels of collagen in hypertrophic scar-derived fibroblasts through inhibiting Smad2/3 phosphorylation and nucleic localization. WG449E blocks HSF migration and invasion by regulating F-actin assignment. In addition, WG449E induces HSF apoptosis through the activation of cleaved-caspase3.

A rare case of association between Budd-Chiari syndrome and sea-blue histiocytosis.

Budd-Chiari syndrome (BCS) is a rare disease characterized by obstruction of hepatic venous outflow tract with diversified etiologies. Sea-blue histiocytosis (SBH) is a kind of storage diseases defined by the deposition of abundant sea-blue histiocytes in various organs and can lead to hepatosplenomegaly, cirrhosis, or even liver failure. The association between BCS and SBH has never been reported before. Here, we report a patient with BCS presenting with hepatosplenomegaly, portal hypertension, and pancytopenia who was later confirmed to also have SBH.