Acute-on-chronic liver failure （ACLF） is a complex clinical syndrome， and early identification and accurate prognostic evaluation are of great importance for patient treatment and management. In recent years， with in-depth research on the pathogenesis of ACLF， multiple prognostic biomarkers have been proposed and used in clinical practice. This article systematically reviews the research advances in prognostic biomarkers for ACLF from the aspects of clinical predictive models， immunological biomarkers， metabolic biomarkers， genetic and epigenetic biomarkers， microbiome-related biomarkers， and emerging technologies such as artificial intelligence and multi-omics， and it also discusses the value and application prospects of these biomarkers in the prognostic evaluation of ACLF and proposes future research directions， in order to provide a scientific and comprehensive reference for clinicians， guide individualized treatment and management of ACLF patients， and finally improve the clinical outcomes of patients.

AIM:To explore the fundus vascular characteristics of healthy individuals based on deep learning techniques, with a view to discovering the range of normal values of the fundus arteries and veins, as well as the relationship between physiological factors, such as gender, age, body mass index(BMI), blood pressure, and fundus vasculature characteristics.METHODS:Fundus images of healthy people were taken from a professional fundus camera, and the subject's blood pressure and laboratory test was collected. Additionally, the fundus arteries and veins were segmented by the improved U-Net model, and the color, morphology and Haralick texture features of the vessels were extracted from computer vision technology.RESULTS:A total of 4 487 cases fundus images were taken and 326 cases with healthy and clear fundus images were screened, including 200 males and 126 females. There were differences in the morphology, color, and textural characteristics of the left and right eyes, as well as of the fundus arterioles and veins, with a mean vessel width(width)of 1.146 in the arteries and 1.430 in the veins, and an arteriovenous ratio about 4:5. Fundus artery and vein characteristics in healthy individuals of different ages(21-30, 31-40, 41-50): compared with the healthy population aged 21-30 and 31-40 years, arterial and venous inverse difference moment(idm), f12 and venous angular second moment(asm)values increased, and arterial and venous contrast(con), entropy(ent), difference entropy(den), and venous sum entropy(sen)values decreased in 41-50 years. Compared with the 21-30 years age group, arterial f12 values increased and venous con values decreased in 31-40 years(all P<0.05). Fundus vascular characteristics of healthy individuals of different sexes: compared with male, fundus arterial and venous sum average(sav), sum variance(sva)values, arterial curved values, and venous b mean, bsd, variance(var), sen, ent values increased in female, while venous area value of female decreased(all P<0.05). There were no statistically significant differences in fundus arteriosus and venous features in healthy subjects with different levels of BMI(all P>0.05). Fundus characteristics of healthy people with different degrees of blood pressure: there were statistically significant differences in fundus arteriosus area, width, and venous con, idm, dva, and den values between the normal blood pressure and high blood pressure groups(all P<0.05).CONCLUSION: The characteristics of the left and right eyes as well as the fundus arteries and veins differ in healthy individuals and correlate with physiological factors such as gender, age and blood pressure, which have the value of a potential microcirculation marker.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

OBJECTIVE To build a standardized simulation teaching system for resident pharmacists and evaluate its effects， and to provide reference for improving the competency of resident pharmacists. METHODS The established simulation teaching system for pharmacy residents’ standardized training in the study included revising the simulation teaching syllabus， setting up simulation teaching courses， implementing the teaching method through “six types of simulations”， applying objective structured clinical examination （OSCE） for assessment， building a simulation teaching team and strengthening the simulation teaching management. The effect evaluation was perfermed with mixed research method， and qualitative and quantitative research methods were used to collect and analyze data and information. RESULTS ＆＆CONCLUSIONS Compared with the traditional teaching system， the passing rate of graduation examination （71.4% vs. 100%） and the score of after-department examination （[ 76.2±7.8） vs. （90.4±4.9）] under the simulation teaching mode were higher； through questionnaire surveys and qualitative interviews， we found that resident pharmacists who went through simulation teaching gave positive feedback on the role and impact of this system. The simulation teaching system can be used with good generalizability for the standardized training of resident pharmacists， and can provide strong basis and support for the high-quality development of hospital pharmacy.

ObjectiveAgrobacterium tumefaciens-mediated transformation （ATMT） of Clonostachys rosea， an endophytic fungus of Glycyrrhiza uralensis seeds， was established and optimized， and orthogonal test was designed to optimize the colonization conditions of C. rosea for G. uralensis seeds， so as to lay foundation for the development of biofertilizer and the breeding of high-quality G. uralensis. MethodThe conditions of ATMT were optimized from three aspects， including the concentration of acetosyringone， co-culture time and the concentration of conidia of recipient fungi. Then， high-quality transformants were selected. Orthogonal test was used to optimize the colonization conditions by taking co-culture temperature， co-culture time and spore concentration as factors and colonization rate as index. ResultWhen spore concentration was 1×10⁷ cfu·mL^-1， acetosyringone concentration was 150 μmol·L^-1 and the co-culture time was 60 h， the transformation efficiency of C. rosea was the highest， which was 135 transformants per 1×10⁷ recipient fungal spores. The accuracy and stability of the transformations were tested by cloning the marker gene green fluorescent protein （GFP） and β-glucuronidase （GUS） staining. When co-culture temperature was 25 ℃， co-culture time was 36 h and the spore concentration was 1×10⁶ cfu·mL^-1， the colonizing rate for C. rosea back dyeing into G. uralensis seeds by seed soaking method was the highest， which was 71.11%. ConclusionThis study successfully establishes stable and efficient technical systems not only of ATMT in C. rosea， but also of colonization of the transformants into G. uralensis seeds， which can lay a foundation for the development of biofertilizer of G. uralensis.

Objective:To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD).Methods:A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results:A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion:The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

Objective:To evaluate the physicochemical properties, degradation and drug release behaviour, cytocompatibility and bacteriostatic properties in vitro of porous magnesium alloy scaffolds containing vancomycin/poly(lactic-co-glycolic acid) (PLGA). Methods:Porous magnesium scaffolds (Mg-2Zn-0.3Ca) were prepared using the template replication technique. The MgF 2 surface layer was obtained by high temperature fluorination. The vancomycin/PLGA porous magnesium alloy drug-loaded scaffolds were obtained by homogeneous lifting after submersion in a dichloromethane solution of PLGA containing vancomycin hydrochloride. According to the products at each stage of the preparation (scaffolds of magnesium alloy, magnesium fluoride alloy, PLGA coated magnesium fluoride alloy, and vancomycin/PLGA magnesium fluoride alloy), they were divided into an Mg group, an MgF 2 group, a PLGA group, and a vancomycin/PLGA group. Immediately after preparation, the material science characterization, degradation rate, drug release rate, antibacterial properties, hemocompatibility, and cell proliferation and differentiation ability of the scaffolds were measured and evaluated. Results:Vancomycin-loaded magnesium alloy scaffolds were successfully prepared with an average porosity of 66.39%. Their degradation rate [(0.540±0.102) mm/year] was significantly lower than that of the Mg ones [(10.048±0.297) mm/year] ( P<0.05). Their pH of degradation in Hank equilibrium salt solution was close to the physiological pH. Their release of vancomycin was fast in the first 48 h and gradually slowed down after 48 h. Their cumulative drug concentration reached a maximum of 43 mg/L at d 11; their vancomycin was still released slowly after d 11. The antimicrobial rate in the vancomycin/PLGA group (97.89%±0.28%) was significantly higher than that in the Mg group (74.92%±2.20%), the MgF 2 group (78.46%±2.59%) and the PLGA group (61.08%±4.21%) ( P<0.05). Their hemolysis rate (0.55%) was much lower than the requirement of ISO 10993-4 (5%). The extract liquid from them promoted the proliferation of rat bone marrow mesenchymal stem cells (BMSCs), showing a gradually increased proliferation rate from d1 (104.80%±5.13%) to d3 (112.36%±2.07%) and d7 (127.79%±4.61%). The calcium nodules in BMSCs were significantly increased at d 14, with an OD value of absorbance of 1.189±0.020, significantly higher than that in the Mg group (0.803±0.020), the MgF 2 group (0.878±0.028) and the PLGA group (0.887±0.026) ( P<0.05). Conclusion:Vancomycin/PLGA-loaded porous magnesium alloy scaffolds exhibit good material properties, antibacterial properties, biocompatibility and osteogenic properties in vitro.

Objective:To analyze the clinical and pathological features and gene mutations of pancreatic acinar cell carcinoma (PACC).Methods:Clinical data of 34 patients with PACC admitted to the Department of Pancreatic Surgery of the First Affiliated Hospital of Naval Medical University from December 2009 to July 2018 were retrospectively analyzed to summarize its clinical characteristics, and the expressions of α1-ACT, CaM5.2, Syn and CgA in pancreatic tumor tissues were detected by immunohistochemistry. Next-generation gene sequencing technology was used to detect gene mutations in tumor specimens.Results:Among the 34 PACC patients, 23(68%) were males and 11(32%) were females; the age ranged from 25 to 75 years, with an average age of 54 years. The first symptom was abdominal pain or distension in 21 cases (62%), skin or scleral yellow staining in 4 cases(12%), and 9 cases(26%) were found in routine physical examination. BMI was 17.6-34.0 kg/m 2, of which 3 cases (9%) were <18.5 kg/m 2, 23 cases (68%) were 18.5-24.0 kg/m 2, and 8 cases (23%) were >24.0 kg/m 2. Preoperative examination showed elevated CA19-9 in 7 cases (20.6%), elevated CEA in 3 cases (8.8%), and elevated AFP in 7 cases (20.6%). Blood amylase was 16-247 U/L, with an average of 80 U/L. Enhanced CT showed that the lesion was irregular in shape, showing inhomogeneity and slightly low density, with areas of cystic degeneration and necrosis. The tumor was located in the head of the pancreas in 14 cases (41%), the body and tail of the pancreas in 19 cases (56%), and the neck of the pancreas in 1 case (3%). The largest tumor diameter was 1.5-15.5 cm, with an average of 5.4 cm. Postoperative pathologic stage I was confirmed in 4 cases (12%), stage Ⅱ in 14 cases (41%), stage Ⅲ in 14 cases (41%) and stage Ⅳ in 2 cases (6%). Immunohistochemical results showed that both α1-ACT and CaM5.2 were positively expressed (100%). Syn was positive in 8 cases (23.5%) and CgA was positive in 6 cases (17.6%). Ki-67 index was from 9% to 70%, with an average of 41%. Gene sequencing of pancreatic tumor tissue from 6 patients showed BRCA2 mutation in 2 patients (7155C>G), K-ras mutation in 1 patient (35G>T), RET mutation in 1 patient (200G>A), and LKB1 mutation (234G>T) in 1 patient, and one double mutation of K-ras and RET (35G>A, 1 798C>T). 30 patients were followed up, and the median survival was 38.3 months. Conclusions:PACC was a rare pancreatic tumor with no specific clinical manifestations. The positive expression rates of α1-ACT and CAM5.2 in tumor tissues were 100%. BRCA2, K-ras, RET and LKB1 were common gene mutations.

Objective:To investigate the knowledge level of hospice care and the related influencing factors among health providers in Shanghai.Methods:From November to December 2019,a questionnaire survey on the hospice care knowledge was conducted among 7 074 health providers from 223 registered hospice care clinics or institutions in 16 districts of Shanghai.Results:A total of 7 027 valid questionnaires were recovered, with an effective recovery rate of 99.3%. Among the 7 027 responders, there were 1 460 males (20.8%) and 5 567 females (79.2%) with an mean age of (36.9±9.3) years; 2 682 nurses (38.2%) and 2 442 doctors (34.8%); 5 065 (72.1%) from community health service centers; 2 982 (42.4%) involving in hospice care services and 4 039 (57.5%) willing to work in hospice care. The average score of hospice care knowledge was (8.9±2.6), and the average accuracy for questions was 59.0%. Health providers had the highest awareness rate for the composition of hospice care professional team (93.9%, 6 597/7 027) and the lowest awareness rate for the emotional commitment in hospice care service (16.6%, 1 165/7 027). Health providers with junior colleges degree ( B=-0.429), vocational college degree and below ( B=-0.544), nurses ( B=-0.652), working in suburban areas ( B=-0.278), social office ( B=-0.891), without witness of dying process of end-of-life patients ( B=-0.329), not involving in hospice care services ( B=-0.283), and not willing to participating in hospice care ( B=-0.820) had low knowledge scores ( P<0.05). Conclusions:The overall level of hospice care knowledge of health providers in Shanghai is generally at a medium level, and the training of hospice care knowledge should be strengthened for the better development of hospice care.