ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

Objective:To construct an evaluation index system for rural order-oriented general practice residents based on Entrustable Professional Activities (EPAs) and conduct an empirical analysis. ?Methods:A mixed-methods study design was adopted (November 2022-April 2023). The preliminary draft of the index system was developed through literature review and group discussions, then refined and improved via two rounds of expert consultation using the Delphi method. The analytic hierarchy process (AHP) was applied to determine the weight of each index. Meanwhile, questionnaires were distributed to 181 participants, including general practitioners from general hospitals, general practitioners from community hospitals, and general practice residents. The scores of the three groups regarding the importance and feasibility of the indices were compared. Ten general practitioners of the above three types were selected for semi-structured interviews on their cognitive and practical aspects of the system. ?Results:The positive coefficients of the two rounds of expert consultation were 16/17 and 16/16, respectively. The expert authority degree was >0.70, and the test of coordination coefficient was statistically significant ( P<0.05). Finally, an index system consisting of 20 first-level indices and 56 second-level indices was established. In terms of weight, among the first-level indices,"EPA1: Information Acquisition"had the highest weight (0.11), while"EPA12: Clinical Research"had the lowest (0.02). Among the second-level indices, "Medical History Taking" and "Physical Examination" under EPA1 had the highest weight (both 0.056), while "Healthcare for Patients with Severe Mental Illness" and "Healthcare for Disabled and Handicapped Populations" under EPA15 had the lowest (both 0.003). The 181 participants gave scores ranging from 4.49 to 4.92 for the importance of the 20 first-level indices and from 4.16 to 4.81 for their feasibility. Only for" EPA19: Common Diseases in Primary Care and Health Management", the feasibility score given by general practitioners from community hospitals was higher than that from general hospitals ( t=2.157, P=0.032); no statistically significant differences were observed among the groups for the other indices ( P>0.05).The interview results showed that general practitioners have a relatively high level of recognition for this system, but there is still room for improvement in its practical application.? Conclusions:The evaluation index system for rural order-oriented general practice residents constructed based on EPAs has high reliability, and it is consistently recognized by different types of general practitioners. It can provide a reference for the cultivation of post competency of this group.?

Objective:To construct an evaluation index system for rural order-oriented general practice residents based on Entrustable Professional Activities (EPAs) and conduct an empirical analysis. ?Methods:A mixed-methods study design was adopted (November 2022-April 2023). The preliminary draft of the index system was developed through literature review and group discussions, then refined and improved via two rounds of expert consultation using the Delphi method. The analytic hierarchy process (AHP) was applied to determine the weight of each index. Meanwhile, questionnaires were distributed to 181 participants, including general practitioners from general hospitals, general practitioners from community hospitals, and general practice residents. The scores of the three groups regarding the importance and feasibility of the indices were compared. Ten general practitioners of the above three types were selected for semi-structured interviews on their cognitive and practical aspects of the system. ?Results:The positive coefficients of the two rounds of expert consultation were 16/17 and 16/16, respectively. The expert authority degree was >0.70, and the test of coordination coefficient was statistically significant ( P<0.05). Finally, an index system consisting of 20 first-level indices and 56 second-level indices was established. In terms of weight, among the first-level indices,"EPA1: Information Acquisition"had the highest weight (0.11), while"EPA12: Clinical Research"had the lowest (0.02). Among the second-level indices, "Medical History Taking" and "Physical Examination" under EPA1 had the highest weight (both 0.056), while "Healthcare for Patients with Severe Mental Illness" and "Healthcare for Disabled and Handicapped Populations" under EPA15 had the lowest (both 0.003). The 181 participants gave scores ranging from 4.49 to 4.92 for the importance of the 20 first-level indices and from 4.16 to 4.81 for their feasibility. Only for" EPA19: Common Diseases in Primary Care and Health Management", the feasibility score given by general practitioners from community hospitals was higher than that from general hospitals ( t=2.157, P=0.032); no statistically significant differences were observed among the groups for the other indices ( P>0.05).The interview results showed that general practitioners have a relatively high level of recognition for this system, but there is still room for improvement in its practical application.? Conclusions:The evaluation index system for rural order-oriented general practice residents constructed based on EPAs has high reliability, and it is consistently recognized by different types of general practitioners. It can provide a reference for the cultivation of post competency of this group.?

Objective:Investigating the migration pattern of microorganisms in the oil-water phase during the prep-aration of sterile test solutions for drugs by extraction method,providing reference for the pre-treatment of oil-based matrix test samples.Methods:Inoculate 6 strains of test bacteria separately into sterile isopropyl tetradecanoate,simulate the sample preparation process of extraction method,and detect the growth status of microorganisms in oil-water phase;Detect the recovery ratio of each test bacterium in the aqueous phase using the extraction method.Select semi-solid oily matrix samples and prepare the test solution using extraction method.Establish a sterility test method according to Part 1101 of the 2020 edition of the Chinese Pharmacopoeia.Results:After extraction,the recovery ratio of each test bacteria in the water phase is in the range of 0.64-0.89.After the oily matrix sample is extracted,the water phase is taken for microbial test,which effectively solves the problems of filter membrane blockage and difficult antibacterial removal,and is beneficial to the subsequent microbial inspection.Conclusion:The extraction method can improve the accuracy and sensitivity of microbial detection in the prepara-tion of test solutions for oily matrix samples.The applicability test of the established sterile inspection method meets the requirements of the Chinese Pharmacopoeia.

Objective:Investigating the migration pattern of microorganisms in the oil-water phase during the prep-aration of sterile test solutions for drugs by extraction method,providing reference for the pre-treatment of oil-based matrix test samples.Methods:Inoculate 6 strains of test bacteria separately into sterile isopropyl tetradecanoate,simulate the sample preparation process of extraction method,and detect the growth status of microorganisms in oil-water phase;Detect the recovery ratio of each test bacterium in the aqueous phase using the extraction method.Select semi-solid oily matrix samples and prepare the test solution using extraction method.Establish a sterility test method according to Part 1101 of the 2020 edition of the Chinese Pharmacopoeia.Results:After extraction,the recovery ratio of each test bacteria in the water phase is in the range of 0.64-0.89.After the oily matrix sample is extracted,the water phase is taken for microbial test,which effectively solves the problems of filter membrane blockage and difficult antibacterial removal,and is beneficial to the subsequent microbial inspection.Conclusion:The extraction method can improve the accuracy and sensitivity of microbial detection in the prepara-tion of test solutions for oily matrix samples.The applicability test of the established sterile inspection method meets the requirements of the Chinese Pharmacopoeia.

Objective To investigate the effect of a three-tier delirium care management process in patients with acute stroke in neurology intensive care unit(NICU).Methods A total of 50 patients with acute stroke admitted to the NICU of the Fourth Hospital of Changsha from May to September 2021 were assigned to the control group.The patients in the control group received routine NICU nursing care to prevent delirium.Another 50 patients with acute stroke admitted to the NICU from December 2021 to April 2022 were assigned to the trial group.They were managed with the three-tier delirium nursing management process on top of the routine NICU nursing care for the control group.The incidence of ICU delirium(DICU),duration of DICU,length of stay in NICU and the incidence of delirium-related adverse events were compared between the two groups.The degree of delirium and cognitive function before and after the intervention were compared between the two groups as well.Results The trial group had significantly shorter duration of DICU and NICU stay(both P<0.05)and lower incidence rate of delirium-related adverse events(P<0.05)compared to the control group.After the intervention,the trial group showed significantly lower scores on the intensive care delirium screening checklist(ICDSC)and significantly higher scores of cognitive function compared to those of the control group(both P<0.05).Conclusion The three-tier delirium nursing management process can lower the occurrence of delirium in NICU patients with acute stroke,shorten the NICU stay,reduce the safety risk in nursing,and improve the cognitive function.

Objective To explore root cause of poor prognosis after successful endovascular treatment(EVT)in patients with acute ischemic stroke with large vascular occlusion(AIS-LVO)of anterior circulation.Methods Patients with AIS-LOV of anterior circulation who received successful EVT(postoperative modified thrombolysis incerebral infarction[mTICI]grade≥2b)were retrospectively and continuously collected in the Department of Neurology of Bozhou People's Hospital from January 2022 to March 2024.The baseline and clinical data of the patients were collected,including gender,age,vascular risk factors(hypertension,diabetes,coronary heart disease,hyperlipidemia,valvular heart disease,atrial fibrillation,smoking,and alcohol consumption),prior stroke or transient ischemic attack,baseline blood pressure,baseline National Institutes of Health Stroke scale(NIHSS)score,laboratory test indicators(pre-operative C-reactive protein and D-dimer,post-operative fasting blood glucose,lipid levels,homocysteine,etc).Meanwhile,the data of perioperative indicators was collected,including the time from onset to admission,the time from admission to puncture,the time from puncture to revascularization,the time from onset to puncture,the time from onset to revascularization,remedial measures(balloon dilation,stent placement,arterial thrombolysis)during the surgery or not,using tirofiban or not,postoperative complications(stroke-related pneumonia,stress ulcers,deep vein thrombosis,acute heart failure or renal failure,etc)or not.The patient's medical history and imaging data were collected,and these indicators were defined and collected,including Alberta stroke program early CT score(ASPECTS),location of occlusion(C1 segment of the internal carotid artery,C2 segment to C7 segment of the internal carotid artery,M1 segment of the middle cerebral artery),and the trial of org 10172 in acute stroke treatment(TOAST)classification and a postoperative transformation of cerebral infarction after ischemic stroke and symptomatic intracranial hemorrhage or not.According to the modified Rankin scale(mRS)score at 90 d after surgery,all patients were divided into poor prognosis group(mRS score≥ 3)and good prognosis group(mRS score≤2).The baseline and clinical data of two groups were compared using univariate analysis.Variables with P＜0.1 in the univariate analysis were selected as independent variables,and the poor prognosis was used as the dependent variable.Further,multivariate Logistic regression analysis was performed to identify the influencing factors of poor prognosis after EVT.Results Finally,a total of 192 patients with AIS-LVO of anterior circulation who received successful revascularization were included in this study.There were 101 male patients and 91 female patients.The poor prognosis group had 102 cases and the good prognosis group had 90 cases.Univariate analysis showed that the poor prognosis group had statistically significant differences with the good prognosis group in terms of age(Z=-3.088,P=0.002)and age distribution(x2=13.457,P=0.001),fasting blood glucose(Z=-3.347,P=0.001),baseline NIHSS score(Z=-4.469,P＜0.01),location of occlusion(x2=10.488,P=0.005),transformation of hemorrhage after ischemic stroke(x2=16.943,P＜0.01),and symptomatic intracranial hemorrhage(X2=25.449,P＜0.01),and the baseline ASPECTS of the poor prognosis group was significantly lower than that of the good prognosis group(Z=-4.547,P＜0.01).There were no significant differences in other baseline and clinical data(all P＞0.05).Further multivariate Logistic regression analysis showed that age＞80 years(OR,3.224,95％CI 1.033-10.058,P=0.044),baseline NIHSS score(OR,1.102,95％CI 1.013-1.199,P=0.023),baseline ASPECTS(OR,0.375,95％CI 0.212-0.665,P=0.001),and symptomatic intracranial hemorrhage(OR,7.127,95％CI 1.296-39.203,P=0.024)were independent influencing factors of poor prognosis.Conclusion The independent factors of 90 d poor prognosis after successful EVT in patients with AIS-LVO of anterior circulation are age＞80 years,baseline NIHSS score,baseline ASPECTS,and symptomatic intracranial hemorrhage.

Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T＞C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.

Objective:To investigate the surgical outcome and prognostic factors of para-split laminotomy for removal of lumbar spinal canal tumors.Methods:Retrospectively review the clinical data of 35 patients suffering lumbar spinal canal tumors, who underwent the para-split laminotomy for tumor resection in Department of Neurosurgery, Clinical Medical College of Yangzhou University from October 2016 to August 2019, including 16 males and 19 females, and the age was(40.1±10.6)years. Intraoperative blood loss, operation time, tumor resection, tumor pathological results, perioperative complications were observed. Follow-up situations, including tumor recurrence, bony fusion of laminae and spinal stability. Follow-up using outpatient examination and telephone interview was performed by the end of August 2022. The JOA back pain scoring system was used to evaluate the neurological function of the spinal cord, and paired t-test were performed to compare the overall preoperative and postoperative spinal cord neurological function scores. Linear regression and multiple linear regression were used to analyze the prognostic factors. Measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and the comparison before and after operation was performed by paired t-test. Mearsurement data of skewed distribution were expressed as M( Q1, Q3). Count data were expressed as cases. Results:The tumors of 35 patients were resected completely. The median blood loss was 100(75, 140)mL and the average operative duration was (181.1±42.7) min. The postoperative pathological results were as follows: 24 neurilemmomas, 6 meningiomas, 4 ependymomas and 1 neurofibroma. There were no surgery-related complications occurred. The postoperative follow-up ranged from 36 to 69 months, with no tumor recurrence or spinal instability, and bony fusion of laminae seen in some patients on CT imaging. The overall spinal cord neurological function scores of pre and post operation were(19.5±3.4)versus(25.4±2.2), Paired t-test analysis revealed a significant difference between the overall postoperative spinal cord neurological function scores and the preoperative scores, and the postoperative scores were better than the preoperative scores( P<0.05). Multiple linear regression analysis showed a positive correlation between preoperative JOA scores and postoperative JOA scores, and postoperative JOA scores has negative correlation with tumor volume and the age at the time of operation ( P<0.05). Conclusion:Para-split laminotomy with less damage to the posterior spinal structures can effectively improve the neurological function of the spinal cord and protect the stability of the lumbar spine in patients with lumbar spinal canal tumors, and the better the preoperative neurological function of the spinal cord, the better the prognosis of patients, and the smaller the tumor volume, the better the prognosis.

Objective: To investigate the effects of continuous goal-directed analgesia on fluid resuscitation during shock stage in patients with massive burns, providing a basis for rational optimization of analgesia protocols in patients with burn shock. Methods: A retrospective case series study was conducted. One hundred and thirty-six patients with massive burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital from January 2015 to December 2020, and the patients were divided into continuous analgesia (CA) group (68 cases,with average age of 44 years old) and intermittent analgesia (IA) group (68 cases,with average age of 45 years old) according to whether sufentanil injection was continuously used for intravenous analgesia during the shock stage. The patients in the 2 groups were predominantly male. Before and at 72 h of treatment, the severity of disease and trauma pain of patients in the 2 groups were scored by the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and the visual analogue scale (VAS). Hematocrit, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), oxygen saturation in central venous blood (ScvO₂), rehydration coefficient, blood lactate value, hourly urine output, and the adverse reactions such as hypotension, nausea, vomiting, dizziness, skeletal muscle tonicity, respiratory depression, bradycardia, pruritus, and drug addiction of patients in the 2 groups during the treatment were recorded at the 1^st, 2^nd, and 3^rd 24 h post-injury. Data were statistically analyzed with analysis of variance for repeated measurement, paired or independent sample t test, Bonferroni correction,chi-square test and Mann-Whitney U test. Results: Before treatment, APACHE Ⅱ and VAS scores of patients in the 2 groups were close (with t values of -0.67 and 0.32, respectively, P>0.05); At 72 h of treatment, APACHE Ⅱ and VAS scores of patients in CA group were 8.5±2.2 and 2.5±1.6, both of which were significantly lower than (15.2±3.0) and (7.9±2.0) of patients in IA group, respectively (with t values of -14.94 and -17.46, respectively, P<0.01). Compared with the pre-treatment period, the APACHE Ⅱ and VAS scores of patients in IA group decreased significantly at 72 h of treatment (with t values of 11.35 and 30.59, respectively, P<0.01); the changes in APACHE Ⅱ and VAS scores of patients at 72 h of treatment in comparison with those of patients before treatment in CA group were all similar to those of patients in IA group (with t values of 4.00 and 4.82, respectively, P<0.01). Compared with those of patients in IA group, there were no significant changes in CVP, hematocrit, heart rate, ScvO₂, and MAP of patients in CA group at all three 24 h post-injury (with t values of <0.01, 0.12, 2.10, 1.55, 0.03; 0.13, 0.22, <0.01, 0.17, 0.49; 0.63, 0.06, 0.04, 2.79, and 2.33, respectively, P>0.05). Compared with those of patients in IA group at the 1^st 24 h post-injury, CVP, ScvO₂ and MAP of patients were significantly higher at the 2^nd and 3^rd 24 h post-injury (with t values of -10.10, -9.31, -8.89; -10.81, -4.65, and -9.43, respectively, P<0.01), and the heart rate of patients was significantly lower at the 2^nd and 3^rd 24 h post-injury (with t values of 7.53 and 7.78, respectively, P<0.01), and the hematocrit of patients decreased significantly only at the 3^rd 24 h post-injury (t=15.55, P<0.01); the changes of CVP, ScvO₂, MAP and heart rate of patients at the 2^nd and the 3^rd 24 h post-injury, and HCT of patients at the 3^rd 24 h post-injury, in comparison with those of patients at the 1^st 24 h post-injury in CA group were similar to those of patients in IA group (with t values of -12.25, -10.24, -8.99, 9.42, -8.83, -7.53, -11.57, 10.44, and 12.91, respectively, P<0.01). Compared with those of patients in IA group, the rehydration coefficient of patients in CA group was significantly higher only at the 3^rd 24 h post-injury (t=5.60, P<0.05), blood lactate value of patients in CA group was significantly lower at the 1^st and 2^nd 24 h post-injury (with t values of 4.32 and 14.52, respectively, P<0.05 or P<0.01), the hourly urine output of patients in CA group increased significantly at the 1^st, 2^nd, and 3^rd 24 h post-injury (with t values of 24.65, 13.12, and 5.63, respectively, P<0.05 or P<0.01). Compared with the those of patients at the 1^st 24 h post-injury, the rehydration coefficient of patients in IA group decreased significantly at the 2^nd and the 3^rd 24 h post-injury (with t values of 33.98 and 36.91, respectively, P<0.01), the blood lactate values of patients in IA group decreased significantly at the 2^nd and the 3^rd 24 h post-injury (with t values of 8.20 and 11.68, respectively, P<0.01), and the hourly urine output of patients in IA group was significantly increased at the 2^nd and the 3^rd 24 h post-injury (with t values of -3.52 and -5.92, respectively, P<0.01); the changes of rehydration coefficients and blood lactate values of patients at the 2^nd and the 3^rd 24 h post-injury in comparison with those of patients at the 1^st 24 h post-injury in CA group were similar to those of patients in IA group (with t values of 35.64, 33.64, 9.86, and 12.56, respectively, P<0.01), but hourly urine output of patients in CA group increased significantly only at the 3^rd 24 h compared with that of patients at the 1^st 24 h post-injury (t=-3.07, P<0.01). Adverse reactions such as hypotension, nausea, vomiting, dizziness, bradycardia, and pruritus occurred rarely in patients of the 2 groups, and none of the patients had skeletal muscle tonicity, respiratory depression, or drug addiction. The incidence of adverse reactions of patients in CA group was similar to that in IA group (χ²=0.08, P>0.05). Conclusions: Continuous goal-directed analgesia can effectively relieve pain and improve vital signs of patients with large burns. Meanwhile it has little impact on volume load, which can assist in correcting ischemia and hypoxia during the shock period and help patients get through the shock period smoothly.
Adult ; Analgesia ; Burns/therapy* ; Fluid Therapy ; Goals ; Humans ; Male ; Middle Aged ; Pain ; Resuscitation ; Retrospective Studies ; Shock/therapy*