Skin wounds are global public problems,especially in terms of the difficult healing of chronic wounds,which may seriously affect patients'lives.Most skin-wound animal models are currently established by physical method,and different animal models have different biological characteristics.This review therefore classifies mouse,rat,and other animal models of skin wounds according to the literature,summarizes and analyzes the construction of skin-wound animal models based on physical method and evaluation indicators,and considers the advantages and disadvantages of different animal models,to provide a basis for the rational construction of skin-wound animal models and drug research and development.

Objective To explore the correlation between the expression of long non-coding RNA(lncRNA)brain ischemia-related factor(BIRF)and focally amplified lncRNA on chromosome 1(lncRNA FAL1)in serum and the degree of white matter lesions(WML)in patients with cerebral small vessel disease(CSVD).Methods From June 2021 to June 2023,102 CSVD patients admitted to Affiliated Hospital of Chengde Medical University were collected,and these patients were grouped into WML group(n=72)and non WML group(n=30)based on WML diagnostic criteria.According to the Fazekas score,the WML group was further grouped into mild WML group(n=24),moderate WML group(n=36)and severe WML group(n=12).Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was applied to detect the levels of lncRNA BIRF and lncRNA FAL1 in serum.Pearson correlation was applied to analyze the correlation between serum lncRNA BIRF and lncRNA FAL1 levels.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum lncRNA BIRF and lncRNA FAL1 levels for severe WML in CSVD patients.Results The age(70.50±5.86 years),history of hypertension(Yes/No,43/29),history of diabetes(Yes/No,45/27),IL-33(68.35±6.80 pg/ml),IL-18(97.78±9.65 ng/L),ubiquitin carboxyl terminal hydrolase L1(UCH-L1)(0.29±0.10 μg/L)and lncRNA BIRF level(2.45±0.30)of patients in the WML group were higher than those in the non WML group(67.10±5.76 years,11/19,9/21,62.48±6.13 pg/ml,92.56±9.37 ng/L,0.24±0.06 μg/L,1.02±0.11),while the expression of serum lncRNA FAL1(0.52±0.10)was lower than that in the non WML group(1.04±0.15),with significant differences(t=2.683,4.518,8.978,4.085,2.510,2.550,25.346,20.500,all P<0.05).The serum lncRNA BIRF levels of CSVD patients in the mild,moderate and severe WML groups(2.23±0.23,2.47±0.31,2.82±0.42)were increased sequentially,while the expression of serum lncRNA FAL1(0.60±0.15,0.51±0.09,0.40±0.04)was decreased sequentially,with significant differences(F=14.913,13.899,all P<0.05).Pearson correlation analysis,the serum levels of lncRNA BIRF and lncRNA FAL1 in patients with WML were negatively correlated(r=-0.603,P<0.001),serum lncRNA BIRF was positively correlated with Fazekas score in WML patients(r=0.483,P<0.001),but serum lncRNA FAL1 was negatively correlated with Fazekas score(r=-0.507,P<0.001).The AUCs of serum lncRNA BIRF and lncRNA FAL1 levels alone and both combination for predicting severe WML in CSVD patients were 0.756(0.641～0.850),0.839(0.733～0.915)and 0.892(0.796～0.953),respectively,and the combination of the two was superior to the detection of serum lncRNA BIRF alone(Z=2.111,P=0.035).Conclusion The serum lncRNA BIRF level is increased and lncRNA FAL1 is reduced in patients with CSVD and WML,and both are related to the degree of WML in CSVD patients.

Objective:To investigate the safety and efficacy of maribavir for the treatment of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study retrospectively analyzed the clinical characteristics and outcomes of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allo-HSCT treated with maribavir at Hebei Yanda Lu Daopei Hospital from April 2024 to September 2024.Result:A total of 25 patients received maribavir, including 21 haploidentical transplants, two sibling HLA-matched transplants, and 2 HLA-matched unrelated transplants. Among them, 21, 2, and 2 patients received the first, second, and third transplants, respectively. The median time to the onset of CMV viremia and CMV disease was 120.5 (6-298) days post-transplantation. The median peak plasma CMV copy number was 6 400 copies/ml (range: 1 100-650 000 copies/ml). Six patients were diagnosed with CMV disease. Maribavir was administered after a median of 9.5 (1-41) days after CMV infection. The median duration of maribavir administration was 11.5 (6-43) days. Post-treatment, maribavir was effective in 25 (100%) patients. Two patients experienced grade 1 taste abnormalities, and one patient experienced grade 2 myelosuppression.Conclusion:The application of maribavir after allo-HSCT for treating refractory, drug-intolerant CMV viremia and CMV disease is safe and effective.

Objective:To investigate the safety and efficacy of maribavir for the treatment of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:This study retrospectively analyzed the clinical characteristics and outcomes of CMV viremia and CMV disease refractory or intolerant to conventional antiviral drugs after allo-HSCT treated with maribavir at Hebei Yanda Lu Daopei Hospital from April 2024 to September 2024.Result:A total of 25 patients received maribavir, including 21 haploidentical transplants, two sibling HLA-matched transplants, and 2 HLA-matched unrelated transplants. Among them, 21, 2, and 2 patients received the first, second, and third transplants, respectively. The median time to the onset of CMV viremia and CMV disease was 120.5 (6-298) days post-transplantation. The median peak plasma CMV copy number was 6 400 copies/ml (range: 1 100-650 000 copies/ml). Six patients were diagnosed with CMV disease. Maribavir was administered after a median of 9.5 (1-41) days after CMV infection. The median duration of maribavir administration was 11.5 (6-43) days. Post-treatment, maribavir was effective in 25 (100%) patients. Two patients experienced grade 1 taste abnormalities, and one patient experienced grade 2 myelosuppression.Conclusion:The application of maribavir after allo-HSCT for treating refractory, drug-intolerant CMV viremia and CMV disease is safe and effective.

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*

Objective:To investigate the effect of circadian rhythm changes on the expression of retinoic acid-related orphan receptors (RORs) and the RORs agonist SR1078 on corneal epithelial wound repair.Methods:A total of 228 SPF C57BL/6 female mice aged 6-8 weeks old were selected, and 180 mice were divided into the normal circadian rhythm group, full-day group, full-night group, 12-hour reversed circadian rhythm group and 3-week reversed circadian rhythm group, with 36 mice in each group.The remaining 48 mice were randomly divided into phosphate buffered saline (PBS) control group and SR1078 group by random number table method, with 24 mice in each group.According to grouping, the mice were placed in a light box where the light (light intensity of 300 lx) and dark time could be controlled.The light time of the normal circadian rhythm group, the PBS control group and the SR1078 group in the light box was from 7: 00 to 19: 00, and the dark time was from 19: 00 to 7: 00 the next day.According to the Zeitgeber Time method, the starting time of light at 7: 00 was recorded as ZT0, and the time of closing light at 19: 00 was recorded as ZT12.Real-time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of RORα and RORγ mRNA at ZT1, ZT5, ZT9, ZT13, ZT17, ZT21 in the five groups.In the PBS control group and SR1078 group, a golf-like knife was used to establish the mouse corneal epithelial injury model, and the model eyes were administered with drugs once every 6 hours according to the grouping.The corneal epithelial defect area was measured with Adobe Photoshop CC2019 software, and the corneal epithelial defect rate was calculated and compared between the two groups.The correlation between the relative expression levels of RORα and RORγ mRNA in mice corneal epithelium of the five groups and corneal epithelial defect rate in the PBS control group and SR1078 group was analyzed.The corneal epithelium repair was observed by whole cornea spreading and immunofluorescence staining, and the number of corneal epithelial dividing cells in the PBS control group and the SR1078 group was calculated and compared.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Laboratory Animal Ethics Committee of Jinan University (No.JN-A-2002-01).Results:Compared with the normal circadian rhythm group, the relative expression levels of RORα/RORγ mRNA in the full-day group, full-night group, 12-hour reversed cirdian rhythym group and 3-week reversed cirdian rhythym group showed an overall decreasing trend.There was a statistically significant difference in the corneal epithelial defect rate between the PBS control group and the SR1078 group at different time points after modeling ( Fgroup=74.01, P<0.001; Ftime=5 171.48, P<0.001). Twelve hours after modeling, the corneal epithelial defect rate in the SR1078 group was significantly lower than that in the PBS control group, and the difference was statistically significant ( P<0.05). The relative expression levels of RORα and RORγ mRNA in corneal tissue was moderately positively correlated with the corneal epithelial defect rate in mice ( r=0.614, 0.537; both at P<0.01); The regression equation of the straight line between the relative expression level of RORα mRNA and the change in corneal epithelial defect rate was Y=33.153X-43.052 ( F=20.58, P<0.001), and the linear regression equation between the relative expression level of RORγ mRNA and the change of corneal epithelial defect rate was Y=2.764X-1.364 ( F=13.11, P<0.001). There was a significant overall difference in the number of corneal epithelial dividing cells at various time points following modeling between the PBS control group and the SR1078 group ( Fgroup=160.55, P<0.001; Ftime=83.57, P<0.001). The number of dividing cells in the SR1078 group was significantly less than that in the PBS control group at 24, 30, and 36 hours following modeling, and the differences were statistically significant (all at P<0.05). Conclusions:Circadian rhythm changes reduce the expression of RORα and RORγ mRNA in the mouse cornea.SR1078 can promote the expression of RORα and RORγ mRNA in corneal epithelium to decrease the number of mouse corneal epithelial dividing cells, and inhibit the repair after corneal trauma.

Objective:To investigate the effect of alprostadil combined with metformin in the treatment of diabetic nephropathy.Methods:50 cases of diabetic nephropathy patients were enrolled and then divided equally into the observation group and the control group. The patients in the control group were treated with conventional therapy and metformin, and the patients in the observation group were treated with alprostadil on the basis of the treatment of the control group. Compare the glycemic index, lipid index, renal function index, inflammatory response index, and oxidative stress response index of the two groups of patients before and after the 4-week treatment. The ratio of the number of effective cases (significant + effective) to the total number of cases, i.e., the total effective rate, was used to characterize the treatment effect.Results:The total effective rate in the observation group was higher than that in the control group (88.00% vs. 60.00%, P<0.05). After the 4-week treatment, no adverse effects occurred in either group. Compared with the control group, patients in the observation group had higher fasting blood glucose (FBG), glycosylated hemoglobin(HbA1c), mean blood glucose(MBG), blood glucose fluctuation rate(BGFR), standard deviation of blood glucose(SDBG), triglyceride(TC), total cholesterol(TG), high-density lipoprotein(HDL), low-density lipoprotein(LDL), serum creatinine(Scr), urinary microalbumin(UmALB), glomerular filtration rate(eGFR), albumin/creatinine ratio(ACR), cyclic adenosine monophosphate(cAMP), renin, protein kinase(PKA), epinephrine (E), angiotensin-converting enzyme inhibitor Ⅱ(ACEI Ⅱ), and norepinephrine(NE) were improved(all P<0.05). Conclusions:The effect of alprostadil combined with metformin in the treatment of diabetic nephropathy is accurate, safe, and reliable.

Objective:To provide a standard protocol for the rapid quantitative analysis of neutrophils in inflamed corneas with flow cytometry.Methods:The corneal epithelium layer of 15 C57BL/6 mice (6-8 weeks old) was mechanically scraped off using a golf-like knife to generate a 2 mm wound region.The mouse corneas with intact limbus were cut out at 18 hours after abrasion.After mechanical shredding, the single cell suspension was obtained by collagenase I and DNase digestion.Then, the number of neutrophils in the corneal cells was sorted under the FACSCanto flow cytometer using the gate technique.Another 6 mice were taken and randomized into wounded group and normal group according to a random number table method, with 3 mice in each group.Corneal cell staining was performed using fluorescent-conjugated anti-mouse CD45, Ly6G, and CD11b antibodies.The number of neutrophils in the corneas of the two groups were enumerated and compared.The use and care of the animals complied with the Statement of the Association for Research in Vision and Ophthalmology (ARVO). The study protocol was approved by the Animal Ethics Committee of Medical College of Jinan University (No.JN-A-2002-01).Results:A standard procedure for detecting neutrophils in the cornea by flow cytometry was established.The ratio of CD45 + cells in the total corneal tissue cell population was (20.93±1.72)%.The Ly6G + and CD11b + double positive neutrophil population was sorted in the wounded corneal cell population.The ratios of Ly6G + and CD116 + cells in the CD45 + cells were (75.50±3.25)% and (93.40±4.53)%, respectively, and the ratio of the Ly6G + and CD11b + double positive neutrophils in the total number of CD45 + cells was (67.33±2.80)%.In addition, the number of neutrophils recruited to the cornea at 18 hours after corneal abrasion was (151.47±10.82)%, which was higher than (15.36±1.02)% in the normal cornea ( t=21.689, P<0.01). Conclusions:Flow cytometry can quickly and accurately quantitatively analyze the neutrophil population in the wounded cornea.It provides a rapid quantitative analysis method to further evaluate the changes of neutrophils in corneal inflammation caused by different reasons.

Objective:To explore the clinical effect of "information knowledge belief practice" model, namely "IKAP theory" nursing intervention model on patients with peritoneal dialysis(PD).Methods:The clinical data of 120 patients with PD treated in The Second Hospital of Tianjin Medical University from January 2020 to December 2020 were analyzed retrospectively. The patients were randomly divided into control group and observation group, with 60 cases in each group. In the observation group, there were 32 males and 28 females with an age range of (56.16±10.25) years, including 18 cases of diabetic nephropathy, 22 cases of chronic glomerulonephritis and 20 cases of hypertensive nephropathy. In the control group, there were 34 males and 26 females, with an age range of (56.27±10.34) years, including 14 cases of diabetic nephropathy, 18 cases of chronic glomerulonephritis and 28 cases of hypertensive nephropathy. The patients in the control group were given routine nursing. In addition to the routine nursing, the patients in the observation group also adopted IKAP mode for nursing intervention. The levels of hemoglobin (HB), serum albumin (ALB), comprehensive nutrition assessment score (SGA) and nursing satisfaction of the two groups were compared before and 6 months after the intervention. The comparison of measurement data before and after intervention in the intervention group was analyzed by paired sample t-test. Frequency data were compared and analyzed by Chi-square ( χ2) test. Results:Before the intervention, there was no significant difference in ALB, Hb levels and SGA between the observation group and the control group( t=1.001~1.743, all P>0.05). After the intervention, the SGA score of the observation group was lower than that of the control group, while the levels of ALB and Hb were higher than those of the control group, and the differences between the two groups were statistically significant ( t=3.411~5.050, all P<0.05). The satisfaction of patients in the observation group was 95%, while that in the control group was 78.33%, and the difference between the two groups was statistically significant ( χ2=7.212, P<0.05). Conclusions:For peritoneal dialysis patients, IKAP nursing intervention can not only effectively improve their nutritional status, but also increase their satisfaction with nursing. IKAP nursing intervention model is worthy of clinical promotion.

Objective To explore the key initiatives and effective methods for preparing the constructions of emergency-oriented hospitals under COVID-19 pandemic. Methods The wartime mechanism was strengthened by adhering to unified leadership, trengthening the top-level design and clarifying the division of responsibilities. Objective management was used as a means to take into account the key of personnel allocation and training, prevention and control of hospital infection, transformation of contagious ward, logistic support, equipment and material supply and construction of system and process. Results The preparations and constructions of the emergency-oriented hospitals were completed in 72 hours，which passed the acceptance and inspections from infection control experts，who appraised our work to be “the highest in difficulty, the fastest in project progress and the highest in quality". Totally, upon to the preparations，14 medical teams were set up and the layout process reestablishment of 14 wards was completed, the installation and preparation of nearly 10000 sets/pieces of medical equipment and medical materials were completed as well and more than 80 work systems and process systems for 9 major modules were established. Conclusion The preparations and constructions of emergency-oriented hospitals should be performed upon the thorough implementation of the decisions and arrangements by the municipal Party committee and the municipal government, insisting on the wartime thinking and establishment of high-quality management team and effective goal management focusing on details and actual needs of medical staff.