OBJECTIVE To investigate the potential of low-frequency, low-power ultrasound to enhance the transdermal absorption and efficacy of ketoprofen gel. METHODS Ketoprofen gel was used as a model drug to compare the in vitro transdermal permeation of ultrasound treated group and untreated group. Additionally, a rat model of collagen-induced inflammation provided a basis for evaluating pharmacodynamic differences. Pharmacokinetic studies further elucidated the effects of ultrasound on ketoprofen gel's penetration process. RESULTS Ultrasound treatment enhanced the cumulative transdermal permeation of ketoprofen gel by 3.5-fold over 24 hours compared to untreated. Significant pharmacokinetic improvements in AUC0-t from (4289.02±763.58)ng·h·mL−1 to (11301.10±3386.30)ng·h·mL−1 and a reduction in Tmax from (6.0±1.4)h to (3.0±2.0)h. Ultrasound notably improved the gel's anti-inflammatory effects in the rat model, effectively and rapidly reducing inflammation-induced swelling. CONCLUSION Low-frequency, low-power ultrasound can significantly improve the amount and rate of transdermal absorption of ketoprofen gel and enhance its pharmacological potency, from the aspects of skin permeation tests, pharmacodynamic evaluation, and pharmacokinetic studies, which is an effective penetration enhancer for transdermal administration of ketoprofen gel.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

Objective To investigate the mechanism behind the protective effects of gastrodin against microglia-mediated inflammatory responses following hypoxic-ischemic brain damage(HIBD)in neonatal mice.Methods Thirty-six 10-day-old C57BL/6J mice were randomized into sham-operated group,HIBD(induced by ligation of the left common carotid artery followed by hypoxia for 40 min)group,and HIBD with gastrodin treatment groups(n=12).In gastrodin treatment group,100 mg/kg gastrodin was injected intraperitoneally 1 h before and at 2 and 12 h after hypoxia.After the treatments,the expressions of CCR5,AKT,p-AKT,and TNF-α and the co-expression of IBA1 and CCR5 in the corpus callosum of the mice were detected with Western blotting and immunofluorescence double staining.In a BV2 microglial cell model of oxygen-glucose deprivation(OGD),the effects of pretreatment with gastrodin and Maraviroc(an CCR5 antagonist)on protein expressions of CCR5,AKT,p-AKT,TNF-α and IL-1β were evaluated using Western blotting and immunofluorescence double staining.Results The neonatal mice with HIBD showed significantly increased expressions of CCR5 and TNF-α with lowered p-AKT expression in the brain tissues,and GAS treatment obviously reversed these changes.HIBD also significantly increased the co-expression of IBA1 and CCR5 in the corpus callosum of the mice,which was obviously lowered by gastrodin treatment.In BV2 cells,OGD significantly increased the expressions of CCR5,TNF-α,and IL-1β and decreased the expression of p-AKT,and these changes were inhibited by treatment with gastrodin,Maraviroc or their combination;the inhibitory effect of the combined treatment did not differ significantly from that of gastrodin or Maraviroc alone.Conclusion Gastrodin can produce neuroprotective effects in neonatal mice with HIBD by inhibiting inflammatory cytokine production and activate AKT phosphorylation via inhibiting CCR5.

Background:When colonic adenoma involves diverticulum,inflammation in the diverticulum will increase the risk of adenomatous dysplasia.Therefore,patients with colonic diverticulum adenoma are at a higher risk of colon cancer,and the adenoma needs to be resected to avoid poor outcome and improve prognosis.Aims:To explore the efficacy and safety of endoscopic mucosal resection(EMR)in treatment of colonic diverticulum adenoma.Methods:Fourteen consecutive cases of colonic adenoma near or involving a diverticulum treated by EMR from Jun.2018 to Jan.2022 at the First People's Hospital of Hangzhou Lin'an District were collected,and their clinical characteristics and outcomes were analyzed.The primary outcome was complications,including bleeding,perforation,and electrocoagulation syndrome,while the secondary outcomes were the en bloc resection rate,complete resection rate and local recurrence rate.Results:Among the 14 patients with colonic diverticulum adenoma,13 were type A(near a diverticulum)while 1 was type B(involving a diverticulum).The diameter of the lesion was(0.76±0.25)cm,and the operation time was(19.67±5.33)minutes.The main histological type was tubular adenoma,and the pathological results was intraepithelial neoplasia in most of the cases.Delayed hemorrhage was observed in 1 patient(7.1%),and electrocoagulation syndrome in 1 patient(7.1%).No perforation event occurred.The en bloc resection rate and complete resection rate were 100%.Ten patients accepted reexamination of colonoscopy within 1 year after surgery,and no local recurrence was found.Conclusions:EMR is safe and effective for treatment of colonic diverticulum adenoma.However,patients using antiplatelet drugs and adenoma involving both appendiceal orifice and diverticulum should be alert to postoperative complications.

Objective:To explore the clinical application value of single pass scanning using muti-slice spiral CT for polytrauma patients.Methods:Totally 60 polytrauma patients treated from January to November in 2023 were randomly enrolled in this study. They were categorized into an experimental group and a control group using a random number table, with 30 patients in each group. The patients in the experimental group underwent single pass scaning for the head, neck, chest, and abdomen, whereas those in the control group receiving separate scanning for various parts. Then, the noise, signal-to-noise ratio (SNR), and contrast-to-noise (CNR) of the CT images of both groups were recorded. Furthermore, the objective and subjective evaluation, volume CT dose index (CTDI vol), effective dose ( E), scanning time, and scan ranges of the images were compared between both groups. Results:Compared to the control group, the test group exhibited lower SNR of the head ( t = -5.47, P < 0.05) and higher SNR and CNR of the chest scans ( t = -5.95, -6.15, P < 0.05). Furthermore, the test group demonstrated decreased ED, CTDIvol, scanning time, and scan range, which dropped from 18.53 mSv to 13.81 mSv ( t = 3.29, P < 0.001), from 15.77 mGy to 10.59 mGy ( t = 4.48, P< 0.001), from 31.68 s to 10.97 s ( t = 6.95, P < 0.001), and from 64.92 cm to 45.21 cm ( t = 9.05, P < 0.001), respectively compared to the control group. Conclusions:Single pass CT scanning can reduce E, scanning time, and scan range in the treatment of polytrauma patients while ensuring the high quality of CT images, thus warranting wide clinical applications.

Background:Early diagnosis and treatment can effectively improve the prognosis of colon cancer.Simple,effective and sensitive screening indicators are of great significance for identification of early cancer and precancerous lesions.L-selectin is a cell adhesion molecule,and podocalyxin(PODXL)is its ligand,both of them play key roles in the development of cancer.Aims:To investigate the expression and significance of L-selectin and its ligand PODXL in colon cancer.Methods:A total of 120 cases of pathological specimens(40 hyperplastic polyp,40 colon adenoma,and 40 colon cancer)from Nov.2020 to Nov.2022 at the Frist People's Hospital of Hangzhou Lin'an District and the First Affiliated Hospital of Zhejiang Chinese Medical University were collected,and 20 cases of normal intestinal mucosal tissue were served as controls.qRT-PCR and immunohistochemistry were used to detect the mRNA and protein expressions of L-selectin and PODXL,respectively.Western blotting was used to determine the expressions of L-selectin and PODXL,and their relations with different clinicopathological parameters of colon cancer were analyzed.In addition,60 serum specimens of colon cancer were collected.ELISA was used to detect serum concentrations of L-selectin and PODXL.Results:Expressions of L-selectin and PODXL mRNA and protein in colon adenoma group were significantly higher than those in normal controls and hyperplastic polyp group(P<0.05),and mRNA and protein expressions of L-selectin and PODXL in colon cancer group were significantly higher than those in normal controls,hyperplastic polyp group and colon adenoma group(P<0.05).Significant differences in protein expressions of L-selectin and PODXL were found in different pathological types,lymph node metastasis,Dukes staging in colon cancer(P<0.05).Expression of L-selectin was positive correlated with expression of PODXL in colon cancer(r=0.855,P<0.001).Serum concentrations of L-selectin and PODXL were significantly lower in the initial group than in the relapse group(P<0.05),and serum concentrations of L-selection and PODXL was significantly lower in the non-metastatic group than in the metastatic group(P<0.05).Serum concentrations of L-selectin and PODXL at 3 months after surgery was significantly lower than 3 days after surgery and before surgery(P<0.05).Conclusions:L-selectin and PODXL may be involved in the development and progression of colon cancer.They are carcinogenic proteins,and their detection could provide reference value for the prevention and early diagnosis of colon cancer,and through early screening of lesion could improve the prognosis of colon cancer to a certain extent.

Background:Studies have confirmed that colorectal tumors may be caused by normal mucosa near or inside the diverticulum,and patients with colon diverticulum are more likely to develop colon cancer than those without diverticulum.When colorectal adenoma involves diverticulum,the inflammatory state in the diverticulum will increase the risk of adenomatous dysplasia.Therefore,adenomas involving colon diverticulum are more likely to develop malignant changes,and adenomas involving colon diverticulum need to be resected to avoid colon cancer outcomes.Improved prognosis.Aims:To explore the efficacy and safety of endoscopic mucosal resection(EMR)treatment of colorectal tumors near or involving a diverticulum.Methods:Fourteen consecutive cases of adenoma(near or involving a diverticulum)during EMR treatment from Jun.2018 to Jan.2022 were collected,and analyze their clinical characteristics and outcomes.The main outcomes were adverse events,including bleeding,perforation,and electrocoagulation syndrome,while the secondary outcome was the total resection rate,block resection rate and local recurrence rate.Results:Among the 14 patients with colon adenoma,1 case was inside the diverticulum,13 cases were near the diverticulum,the diameter of the lesion was(0.76±0.25)cm,the operation time was(19.6±5.33)min.The main tissue types were tubular adenomas,and the pathologic characteristics were low grade intraepithelial neoplasia.Among the complications,delayed hemorrhage was found in 1 case(7.1%),the patient had a history of taking antiplatelet drugs(clopidogrel),electrocoagulation syndrome was found in 1 case(7.1%),and appendiceal orifice and diverticulum were involved in this patient,with no perforation event.The whole resection rate and the complete resection rate were 100%(14/14).Within 1 year after surgery,10 patients came to the hospital for re-examination of colonoscopy,and no local recurrence was found.Conclusions:EMR treatment involving colonic diverticulum adenoma is safe and effective.However,patients with adenoma involving antiplatelet drugs and appendiceal orifice and diverticulum should be alert to postoperative complications.

Objective To explore the expression pattern of Micall2a gene during the early development of zebrafish embryos and the effect of this gene on zebrafish vascular development.MethodsWhole embryo in situ hybridization was used to detect Micall2a expression levels at different stages of early embryo development of Tg (fli:GFP) transgenic (labeled with green fluorescent protein) and wild type zebrafish (AB). Micall2a gene expression was downregulated by microinjection of a morpholine antisense oligonucleotide, and real-time fluorescent quantitative PCR was used to detect mRNA expression of the gene at different developmental stages of zebrafish embryos. Laser confocal microscopy was used to observe and analyze vascular phenotypic changes in zebrafish after the downregulation of Micall2a. ResultsMicall2a was expressed in the brain, heart, and vascular system of zebrafish embryos at the 24th, 36th, and 48th hours post fertilization. The mRNA level of Micall2a increased after microinjection of morpholine antisense oligonucleotides, inhibiting vascular development in zebrafish embryos, resulting in internode angiogenesis defects in zebrafish. ConclusionDownregulation of Micall2a expression inhibits the development of blood vessels in zebrafish.

ObjectiveTo investigate the distribution characteristics of hepatitis C virus (HCV) genotypes in patients with hepatitis C in Guizhou, China, and to provide a basis for the prevention and individualized treatment of HCV infection. MethodsA total of 1211 HCV RNA-positive patients with hepatitis C who were treated in Guiyang Public Health Clinical Center from September 2011 to October 2018 were enrolled. PCR direct sequencing was performed to obtain HCV sequences, which were then compared with the known HCV sequences in GenBank to obtain HCV genotypes and subgenotypes. The association of genotype distribution with sex, age, ethnic group, region, and route of infection was analyzed. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsA total of 4 genotypes and 11 subgenotypes were detected among the 1211 individuals with HCV infection, with the main genotypes of 1b (26.84%), 3b (27.17%), and 6a (24.28%). There was a significant difference in the distribution of HCV genotypes between the male and female individuals (χ2=15.428, P=0.009); 29.34% of the male individuals had genotype 3b, and 32.21% of the female individuals had genotype 1b. There was a significant difference in the distribution of HCV genotypes between different age groups (χ2=67.439, P＜0.001); genotype 1b was the main genotype in the individuals aged ≤18 years (66.67%) or ≥60 years (58.93%), genotypes 3b and 6 were the main genotypes in the individuals aged 19-39 years (28.93% and 29.29%, respectively), and genotypes 1b, 3b, and 6 were the main genotypes in the individuals aged 40-59 years (29.54%, 27.33%, and 24.28%, respectively). There was a significant difference in the distribution of HCV genotypes between the individuals with different routes of infection (χ2=153.916, P＜0001); the most common route of infection was intravenous drug addiction (57.97%), followed by sexual contact (8.42%) and invasive cosmetic surgery (8.42%); genotype 3b was the main genotype in the individuals with intravenous drug addiction (31.48%) or invasive cosmetic surgery (32.35%), and genotype 6 was the main genotype in the individuals with sexual contact (36.27%). There was no significant difference in the distribution of HCV genotypes between the individuals in different ethnic groups or from different regions of Guizhou (both P＞0.05). ConclusionThe distribution of HCV genotypes is diverse in Guizhou, and HCV strains with genotypes 3b, 1b, and 6a are the main epidemic strains. Several rare subgenotypes of HCV genotype 6 are observed. There is a significant difference in the distribution of HCV genotypes between the individuals with different ages, sexes, or routes of infection.

Objective To approach the significance of changes of percutaneous-arterial blood carbon dioxide partial pressure difference [P(tc-a)CO2] in liquid resuscitation of patients with septic shock. Methods One hundred and sixty-eight patients with septic shock admitted and treated in the Department of Intensive Care Unit (ICU) of Quzhou People's Hospital from January 2015 to January 2018 were enrolled, and after early goal-directed therapy (EGDT) for 6 hours, according to central venous oxygen saturation (ScvO2) and lactate clearance (LC), they were divided into ScvO2 and LC achievement group (ScvO2 ≥ 0.7 and LC≥10%), ScvO2 achievement group (ScvO2 ≥ 0.7 and LC < 10%), LC achievement group (ScvO2 < 0.7 and LC≥10%), and un-achievement group (ScvO2 < 0.7 and LC < 10%). The mechanical ventilation time, ICU hospitalization time, 28-day mortality, P(tc-a)CO2 etc. were compared among the four groups; the receiver operating characteristic curve (ROC) was used to evaluate the predictive value of P(tc-a)CO2 for 28-day prognosis in patients with septic shock. Results The trends of mechanical ventilation time, ICU hospitalization time, and 28-day mortality were all ScvO2 and LC achievement group < LC achievement group < ScvO2 achievement group < un-achievement group [the mechanical ventilation times (days) were respectively 6.12±2.59, 8.43±3.24, 11.78±4.12, 13.03±4.75, ICU hospitalization times (days) were 10.31±2.32, 13.85±3.56, 16.41±3.83, 18.52±4.05, and 28-day mortality rates were 28.85% (15/52), 40.91% (18/44), 51.28% (20/39), 69.70% (23/33)] and the differences among the four groups were statistically significant (all P < 0.05). After 6 hours of EGDT, the heart rate (HR), lactate (Lac), and P(tc-a)CO2 were lower than those before fluid resuscitation, but the mean arterial pressure (MAP), central venous pressure (CVP), and ScvO2 were higher than those before fluid resuscitation among four groups. Except CVP, the differences of other indicators compared among the ScvO2 and LC achievement group, ScvO2 achievement group, LC achievement group and un-achievement group were statistically significant (all P < 0.05). After 6 hours of EGDT, HR, Lac, P(tc-a)CO2 in ScvO2 and LC achievement group, ScvO2 achievement group and LC achievement group were significantly lower than those in the un-achievement group [HR (bpm): 89.05±29.43, 98.82±30.21, 94.33±28.64 vs. 112.85±32.74, Lac (mmol/L): 2.97±1.95, 3.87±2.32, 2.69±1.52 vs. 4.17±2.44, P(tc-a)CO2 (mmHg, 1 mmHg = 0133 kPa): 7.18±4.61, 12.61±5.34, 9.71±4.11 vs. 16.56±10.19], MAP and ScvO2 were significantly higher than those of the un-achievement group [MAP (mmHg): 88.05±21.67, 77.33±18.56, 83.11±19.71 vs. 70.32±18.79, ScvO2: 0.76±0.14, 0.75±0.16, 0.67±0.14 vs. 0.63±0.18, all P < 0.05]. The P(tc-a)CO2 of 28 days survivors were significantly lower than that of the deaths among four groups (mmHg: 5.78±2.27 vs. 14.14±3.65, 7.07±2.81 vs. 15.06±4.11, 6.35±2.09 vs. 14.94±4.06, 7.93±3.81 vs. 18.34±4.63, all P < 0.05). When P(tc-a)CO2 > 7.24 mmHg predicted 28-day mortality in ScvO2 and LC achievement group, the sensitivity was 89.29%, specificity was 91.45%, and the area under ROC curve (AUC) was 0.86; when P(tc-a)CO2 > 9.46 mmHg predicted 28-day mortality in LC achievement group, the sensitivity was 88.72%, specificity was 85.83% and AUC was 0.91; when P(tc-a)CO2 >12.05 mmHg predicted 28-day mortality in ScvO2 achievement group, the sensitivity was 82.79%, specificity was 86.90% and AUC was 0.79; when P(tc-a)CO2 > 16.22 mmHg predicted 28-day mortality in un-achievement group, the sensitivity was 73.35%, specificity was 80.68% and AUC was 0.68. Conclusion P(tc-a)CO2 can be used as an indicator to evaluate fluid resuscitation effect and prognosis in patients with septic shock.