Clinical heterogeneity and cluster analysis of multiple system atrophy / 中华老年医学杂志

Objective:To examine the clinical subtypes of patients with multisystem atrophy(MSA)that may indicate the prognosis of patients.Additionally, we aim to compare the ability to perform daily activities among patients of each subtype using cluster analysis.Methods:The retrospective analysis included demographic data, clinical symptoms and signs, scale scores, and ancillary examinations of 94 patients diagnosed with multisystem atrophy at Xuanwu Hospital of Capital Medical University.The study aimed to analyze the clinical characteristics of each subtype obtained through clustering.Additionally, a comparison was made between patients with traditional motor subtypes and those with new subtypes in terms of activities of daily living.The study consisted of 94 MSA patients, with an average age of 61 years and a female representation of 51.1%.Using the data collected on the continuum, a full linkage hierarchical cluster analysis was performed to classify MSA patients into four clinical subtypes: gait disorder(17 cases, 18.1%), malignant tonic hyperkinetic with premature haircut(25 cases, 26.6%), intermediate(43 cases, 45.7%), and autonomic benign type(9 cases, 9.6%).Each subtype exhibited various clinical motor and non-motor symptoms, including UPDRS-Ⅲ( χ2=27.90, P<0.001), gait disturbance( χ2=33.23, P<0.001), MoCA( χ2=10.98, P=0.012), HAMA( χ2=12.14, P=0.007), HAMD( χ2=13.62, P=0.003), smell score( χ2=10.16, P=0.017), postural hypotension( χ2=14.59, P=0.028), and a statistically significant difference in the ability to perform daily living score( χ2=25.35, P<0.001).No statistically significant differences in non-motor symptoms and activities of daily living abilities were observed between the cerebellar and Parkinsonian types of traditional motor typing( P>0.05). Conclusions:The hierarchical clustering analysis conducted in this study reveals that the clinical phenotype of MSA provides a more accurate reflection of patients' clinical characteristics and their impact on quality of life compared to the traditional motor phenotype.Additionally, it may help predict variations in the underlying pathological impairment and the rate of disease progression.These findings offer a foundation for precise diagnostic interventions in patients with MSA.

Aucubin inhibits the proliferation of human hepatocellular carcinoma cells line HepG2 / 基础医学与临床

Objective To investigate the effects of aucubin(AU)on the proliferation,apoptosis,and cell cycle of human liver cancer cells line HepG2 and its mechanism of action.Methods HepG2 cells were cultured in vitro,CCK-8 method was applied to screen the optimal dosage concentration of AU.HepG2 cells were randomly grouped into a control group,an AU 12.5 mg/L group(AU L group),an AU 62.5 mg/L group(AU H group),and an AU H+Akt pathway agonist(SC79)group(AU H+SC79 group).The cell proliferation was observed in each group;5-Ethynyl-2′-deoxyuridine(EDU)method was applied to detect cell proliferation;Flow cytometry was applied to detect cell apoptosis and cell cycle;Western blot was applied to detect the expression levels of phosphorylated pro-tein kinase B(p-Akt),Akt,p-MDM2,MDM2,p-p53,and p53 proteins.Results AU concentrations of 12.5 and 62.5 mg/L were selected for subsequent experiments.Compared with 0 mg/L AU,the proliferation of 12.5 and 62.5 mg/L AU cells was obviously reduced(P＜0.05);Compared with the control group,the number of suspended and exfoliated cells in the AU L and AU H groups gradually increased.Cells shrunk and became round.The propor-tion of G0/G1 phase cells,the proportion of EDU positive staining cells increased and the expression level of p-Akt/Akt and p-MDM2/MDM2 proteins decreased.The proportions of S and G2/M phase cells,the rate of cell apoptosis,and the expression level of p-p53/p53 protein all increased(P＜0.05).Compared with the AU H group,the above changes in the AU H+SC79 group were recovered(P＜0.05).After AU treatment,the tumor vol-ume and weight of transplanted nude mice decreased.Conclusions AU may inhibit the proliferation of liver cancer cells,induce cell cycle arrest and apoptosis by regulating the Akt/MDM2/p53 signaling pathway.

Establishment and assessment of a postoperative delirium risk scale for elderly patients undergoing hip and knee replacement / 临床麻醉学杂志

Objective To construct a risk assessment scale for postoperative delirium(POD)in elderly patients undergoing hip and knee joint replacement and evaluate the effect.Methods A total of 474 elderly patients undergoing hip and knee arthroplasty from March 2021 to May 2022 were collected as the training set,and a total of 153 the homogeneous patients from January 2022 to May 2022 were collected as the validation set.The patients were divided into two groups based on whether or not POD occurred:non-POD group and POD group.Risk factors of POD in the training set were analyzed by univariate analysis and multifactorial logistic regression.The consistency of the model was evaluated by Homser-Lemeshow goodness of fit test.The postoperative delirium risk assessment scale was established after the selected variables as-signed value according to OR value,and the predictive efficacy of the scale was evaluated by receiver oper-ating characteristic(ROC)curve.The patients in the training set and the validation set were divided into two groups according to the cut-off value:high-risk and low-risk.The incidence rate of POD with different risk stratification was calculated and the applicability of the risk assessment scale was evaluated.Results Fifty-eight patients(12.2%)with POD in the training set,and nineteen patients(12.4%)with POD in the validation set.Multifactor logistic regression showed that age≥85 years,ASA physical status Ⅲ or Ⅳ,the mini-mental state examination(MMSE)score≤24 points,preoperative sleep disorder,comorbid neu-rological disorders,use of general anesthesia,and non-use of dexmedetomidine were independent risk factors of POD.The POD risk assessment scale was then published based the seven risk factors.The ROC curve showed that the area under the curve(AUC)for this scale to predict the risk of POD was 0.956(95%CI 0.937-0.975),and the risk stratification was performed with a cut-off value of 44.5 points,which divided the patients into low-risk and high-risk.Compared with low-risk,the incidence rate of POD in high-risk patients group was significantly increased(P＜0.001).Conclusion A risk assessment scale based on the seven risk factors:age≥85 years,ASA physical status Ⅲ or Ⅳ,MMSE score≤24 points,preoperative sleep disorder,combined neurological disease,use of general anesthetic modality,and non-use of dexmedetomidine,can effectively identify elderly patients undergoing hip and knee replacement who are at high risk of developing POD.

Comparative Study of the Two High-Efficient Strategies for in vitro Generation of Human Umbilical Cord Blood-derived Natural Killer Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies.@*METHODS@#Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy.@*RESULTS@#After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05).@*CONCLUSION@#The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.

Therapeutic potential and mechanism of Chinese herbal medicines in treating fibrotic liver disease / 中国天然药物

Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness.

Relationship between serum lactate and early prognosis after liver transplantation in children / 中华器官移植杂志

Objective:To explore the relationship between serum lactate level and early prognosis after liver transplantation (LT) in children.Methods:Between January 1, 2018 and December 31, 2020, 675 pediatric LT recipients were recruited. Clinical data were retrospectively reviewed, early postoperative serum lactate level and clearance rate recorded and receiver operating characteristic (ROC) curve plotted for determining optimal cut-off values. The inter-group differences in early postoperative complications and patient/graft survival rates were compared.Results:According to ROC, blood lactate levels >1.99 mmol/L at 12 h postoperatively were associated with early postoperative graft loss (AUC 0.73, 95% CI: 0.62-0.84, P=0.01). Age and weight of recipients in high-level group were 7.17(5.70-10.40) month and 7.00(6.00-8.60) kg and both were significantly lower than those in low-level group [7.80(6.21-13.58) month and 7.20(6.45-9.00) kg]. The inter-group differences were statistically significant ( P=0.017, P=0.034). Blood plasma transfusion volume, red blood cell transfusion volume, portal vein pressure pre-closure, postoperative intensive care unit (ICU) stay, ventilator use time, early allograft dysfunction rate, early postoperative pulmonary infection rate and recipient mortality rate in high-level group were 400 (200-400) ml, 2.00 (2.00-4.00) U, (15.71±4.44) mmHg, 2.50(2.00-3.00) day, 3.81(2.47-8.50) hour, 22.95%(42/185), 16.76%(31/185) and 6.49%(12/185) respectively. The above values were significantly higher than those in low-level group 200(100-400) ml, 2.00 (2.00-3.00) U, (14.69±4.68) mmHg, 2.00(2.00-3.00) day, 3.53(2.34-6.12) hour, 14.69%(72/490), 11.02%(54/490) and 1.43%(7/490) respectively. The inter-group differences were statistically significant ( P<0.001, P=0.014, P=0.015, P=0.037, P=0.043, P=0.011, P=0.045 & P<0.001). The incidence of early postoperative acute cellular rejection was significantly lower in high-level group than that in low-level group [11.89%(22/185) vs 22.86%(112/490)]. The inter-group difference was statistically significant ( P=0.01). The 1/3-month cumulative survival rates of patient/graft were 94.6%, 94.1% and 92.4%, 91.4% in high-level group versus 99.2%, 98.6% and 99.0%, 98.4% in low-level group. There were significant inter-group differences ( P=0, P<0.000 1). With a rising level of lactate at 12 h postoperatively, risk of early graft loss and early recipient mortality spiked markedly ( P<0.05). Conclusions:Serum lactate level post-operation is a valid predictor of early prognosis after LT in children.

Expanding the indications for antiviral therapy for chronic hepatitis B: Advantages and disadvantages / 临床肝胆病杂志

Chronic hepatitis B (CHB) is a chronic progressive disease caused by hepatitis B virus (HBV), and without timely and effective antiviral therapy, it will eventually develop into liver cirrhosis, liver failure or hepatocellular carcinoma (HCC). Early initiation of antiviral therapy can prevent or delay disease progression and greatly reduce the incidence rates of liver cirrhosis, liver failure, and HCC. Due to the limited efficacy of current antiviral drugs, the indications for antiviral therapy are mainly applicable to patients with positive HBV DNA and persistent ALT abnormality and some special populations with HBV infection. However, some patients who cannot reach the criteria for antiviral therapy may have insidious disease progression, leading to adverse clinical outcomes. Therefore, the guidelines and consensus statements in China and globally are constantly expanding the indications for antiviral therapy for CHB, so as to bring benefits to more patients.

Research progress of rapid surgery for hip fracture in elderly patients / 中国修复重建外科杂志

OBJECTIVE@#To review the research progress of rapid surgery for hip fracture in elderly patients.@*METHODS@#The published studies, expert consensus, and guidelines at home and abroad were systematically summarized from the aspects of the characteristics of aging population, the benefits of rapid surgery, the disadvantages of delayed surgery, and the recommendations of current guidelines, so as to further guide clinical practice.@*RESULTS@#Hip fracture is a common fracture type in the elderly population. As elderly patients generally have poor physique and often have a variety of underlying diseases, such as hypostatic pneumonia, bedsore, lower limb vein thrombosis, and other complications in conservative treatment, its disability rate and mortality are high, so surgical treatment is the first choice. At present, most relevant studies and expert consensus and guidelines at home and abroad support rapid surgery, that is, preoperative examination should be started immediately after admission, and adverse factors such as taking anticoagulant drugs, serious cardiovascular diseases, and severe anemia should be clearly and actively corrected, and surgery should be completed within 48 hours after admission as far as possible. Rapid surgery can not only significantly reduce the mortality of patients, but also reduce the length of hospital stay and the incidence of perioperative cognitive impairment, which is conducive to the recovery of patients with pain during hospitalization and postoperative function, and improve the prognosis of patients.@*CONCLUSION@#In order to avoid many problems caused by delayed surgery, the elderly patients with hip fracture should be operated as soon as possible under the condition of actively correcting the adverse factors. Comprehensive evaluation and preparation, the development of an individualized surgical plan, and the formation of a multidisciplinary medical team can reduce surgical risks and improve effectiveness.

Risk factors and their early warning effectiveness for the occurrence of early neurological deterioration in patients with moderate traumatic brain injury / 中华创伤杂志

Objective:To investigate the risk factors and their early warning effectiveness for the occurrence of early neurological deterioration (END) in patients with moderate traumatic brain injury (modTBI).Methods:A retrospective cohort study was conducted to analyze the clinical data of 265 patients with modTBI admitted to the Second Affiliated Hospital of Fuyang Normal University from January 2018 to April 2023. There were 165 males and 100 females, with age range of 20-91 years [(59.5±14.4)years]. The patients were divided into END group ( n=46) (17.4%) and non-END group ( n=219) (82.6%) according to whether the Glasgow Coma Score (GCS) decreased by 2 points or more within 72 hours after injury. Data of the two groups were recorded, including gender, age, basic diseases (hypertension and diabetes), cause of injury (traffic injuries, falls, etc), vomiting before admission, admission GCS, first CT scan time, epilepsy, brain contusion, subarachnoid hemorrhage, types of intracranial hematoma (epidural, subdural, and intracerebral hematoma), types of fracture (skull base fracture and skull fracture), laboratory indicators [platelet count (PLT), blood potassium level, serum total calcium concentration, thrombin time (TT), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), level of fibrinogen (FIB), and level of D-dimer. Correlations between above-mentioned indicators and occurrence of END among modTBI patients were assessed and the independent risk factors were revealed by univariate and multivariate binary Logistic regression analysis. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the early-warning effectiveness of each risk factor for END. Results:Univariate analysis showed that admission GCS, first CT scan time, epidural hematoma, subdural hematoma, intracerebral hematoma, serum potassium level, FIB and D-dimer were statistically correlated with occurrence of END among modTBI patients ( P<0.05 or 0.01). Multivariate binary Logistic regression analysis showed that admission GCS≤10 points ( OR=0.53, 95% CI 0.34, 0.84, P<0.01), first CT scan time≤2.0 hours ( OR=0.58, 95% CI 0.37, 0.92, P<0.05), epidural hematoma ( OR=0.26, 95% CI 0.10, 0.69, P<0.05), intracerebral hematoma ( OR=0.14, 95% CI 0.04, 0.44, P<0.01), level of FIB≤2.3 g/L ( OR=0.34, 95% CI 0.18, 0.64, P<0.01), level of D-dimer>10.4 mg/L ( OR=1.04, 95% CI 1.02, 1.07, P<0.01) were independent risk factors for END among modTBI patients. ROC curve analysis showed that the first CT scan time had relatively higher early warning value (AUC=0.79, 95% CI 0.74, 0.84), level of D-dimer (AUC=0.75, 95% CI 0.70, 0.80) and level of FIB (AUC=0.70, 95% CI 0.65, 0.76) had moderate early warning value, which was higher than that of admission GCS (AUC=0.62, 95% CI 0.56, 0.68), intracerebral hematoma (AUC=0.62, 95% CI 0.56, 0.68) and epidural hematoma (AUC=0.60, 95% CI 0.54, 0.66). The combination of the risk factors revealed superior early warning efficiency for END (AUC=0.90, 95% CI 0.85, 0.93). Conclusions:Admission GCS≤10 points, first CT scan time≤2.0 hours, epidural hematoma, intracerebral hematoma, level of FIB≤2.3 g/L and level of D-dimer>10.4 mg/L are independent risk factors for END among modTBI patients. The early warning value of the first CT scan is the highest, followed by D-dimer and FIB, and the early warning effectiveness of admission GCS, intracerebral hematoma and epidural hematoma is ordinary.The combination of the above risk factors has better early warning efficiency for occurrence of END among modTBI patients.

Effects of MMP14 on CD8+T cell dysfunction in lung cancer patients by regulating mCD100 shedding and sCD100 generation / 免疫学杂志

The study aimed to elucidate the modulatory role of MMP14 on mCD100 shedding and sCD100 production,and its subsequent effects on CD8+T cell dysfunction in lung cancer patients.Total of 56 non-small cell lung cancer(NSCLC)patients were from January 2020 to January 2023 and compared them with 88 healthy controls.Bronchoalveolar lavage fluid(BALF)was obtained from both tumor and non-tumor sites of the patient group.Peripheral blood mononuclear cells(PBMC)were isolated from both groups,and the expression of CD72 and mCD100 in PBMC were assessed via flow cytometry.CD8+T cells from tumor sites were stimulated with recombinant human MMP14 and CD100.Post-cultivation,supernatant levels of TNF-α and IFN-γ were determined by ELISA,while granulysin B and perforin levels were analyzed through an ELISPOT assay.The rate of target cell death was also observed.Data showed no significant difference in the proportion of CD3+mCD100+,CD3+CD72+ cells,and the average fluorescence intensity of CD72 in CD100 and CD3+ monocytes in CD3+CD8+T cells between the patient and control groups.However,as compared with non-tumor sites,these indexes of tumor sites were significantly elevated.Stimulation with CD100 led to increase in IFN-γ,TNF,perforin,and granulozyme B secretion levels in CD8+T cells.After MMP14 stimulation,the proportions of CD3+mCD10 0+ and target cell death,along with sCD100,TNF-α,IFN-γ,and granulozyme B levels in CD8+T cells from NSCLC tumor sites,were notably increased.Interestingly,the addition of anti-CD100 to MMP14-stimulated CD8+T cells resulted in a significant drop in the levels of sCD100,TNF-α,IL-1β,and granulozyme B,as well as in the proportion of target cell death.Taken together,in NSCLC patients,the inhibition of CD100 shedding in CD8+T cells at tumor sites and the blockade of sCD100 production result in impaired CD8+T cell killing function.MMP14 appears to enhance mCD100 shedding and sCD100 production,thereby potentially restoring the cytotoxic function of CD8+T cells against primary NSCLC cells.

Clinical effects of free transplantation of expanded thoracodorsal artery perforator flaps in reconstructing cervical cicatrix contracture deformity after burns / 中华烧伤杂志

Objective: To explore the clinical effects of free transplantation of expanded thoracodorsal artery perforator flaps in reconstructing cervical cicatrix contracture deformity after burns. Methods: A retrospective observational study was conducted. From May 2018 to April 2021, 11 patients with cervical cicatrix contracture deformity after burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 3 males and 8 females, aged 5 to 46 years, with a course of cervical cicatrix contracture deformity of 5 months to 8 years. The degree of cervical cicatrix contracture deformity was degree Ⅰ in one patient, degree Ⅱ in nine patients, and degree Ⅲ in one patient. In the first stage, according to the sizes of neck scars, one rectangular skin and soft tissue expander (hereinafter referred to as expander) with rated capacity of 200 to 600 mL was placed in the back. The expansion time was 4 to 12 months with the total normal saline injection volume being 3.0 to 3.5 times of the rated capacity of expander. In the second stage, free expanded thoracodorsal artery perforator flaps with areas of 10 cm×7 cm to 24 cm×13 cm were cut out to repair the wounds with areas of 9 cm×6 cm to 23 cm×12 cm which was formed after cervical cicatectomy. The main trunk of thoracodorsal artery and vein were selected for end-to-end anastomosis with facial artery and vein, and the donor sites were directly closed. The survival of flaps and healing of flap donor sites were observed on the 14th day post surgery. The appearances and cicatrix contracture deformity of the flaps, recovery of cervical function, and scar hyperplasia of donor sites were followed up. Results: On the 14th day post surgery, the flaps of ten patients survived, while ecchymosis and epidermal necrosis occurred in the center of flap of one patient and healed 2 weeks after dressing change. On the 14th day post surgery, the flap donor sites of 11 patients all healed well. During the follow-up of 6-12 months post surgery, the flaps of ten patients were similar to the skin around the recipient site in texture and color, while the flap of one patient was slightly swollen. All of the 11 patients had good recovery of cervical function and no obvious scar hyperplasia nor contracture in the flaps or at the donor sites. Conclusions: Application of expanded thoracodorsal artery perforator flaps can restore the appearance and function of the neck, and cause little damage to the donor site in reconstructing the cervical cicatrix contracture deformity after burns, which is worthy of clinical reference and application.

Effect of allograft type on the prognosis of pediatric liver transplantation in low-body-weight recipients / 中华器官移植杂志

Objective:To investigate the effects of different donor types on the prognosis of pediatric liver transplant recipients with low-body-weight (≤6 kg).Methods:The clinical data of low-body-weight pediatric liver transplant recipients from the Department of Pediatric Organ Transplantation, Tianjin First Central Hospital from January 2013 to June 2021 were retrospectively analyzed.The recipients were divided into living donor group, split donor group and whole liver group according to the donor type.The basic information of donors and grafts, preoperative and intraoperative information of recipients, major postoperative complications and survival rates of recipients and grafts were compared.Results:A total of 244 recipients were enrolled in this study, including 183 cases in the living donor group, 18 cases in the split donor group and 43 cases in the whole liver group.There were no statistical differences in the preoperative data of the three groups, including gender, age, body weight, blood type matching, primary disease, Child-pugh grading, and pediatric end-stage liver disease score (PELD). The incidence of hepatic artery thrombosis (HAT) in the three groups was 2.2%, 16.7% and 25.6%, respectively, the difference was statistically significant between the living donor group and the split donor group ( P=0.017) as well as the whole liver group ( P<0.001). There was no significant difference between the latter two groups ( P=0.525). The median follow-up time was 37, 31 and 47 months, respectively.The 1-year and 3-year cumulative graft survival rates were 92.9%, 91.3%, 83.3% and 83.3% 76.7%, 76.7% ( P=0.016), respectively.There was statistical difference between the living donor group and the whole liver group ( P=0.004), and no statistical difference between the split donor group and the living donor group ( P=0.212) as well as the whole liver group ( P=0.610). The 1-year and 3-year cumulative recipient survival rates in the three groups were 92.9%, 91.3%, 94.4% and 94.4%, 86.0%, 86.0%, respectively, and there was no statistical difference among the three groups ( P=0.463). Multivariate analysis suggested that donor age and anhepatic phase were independent risk factors for HAT.Cold ischemia time, volume of intraoperative blood transfusion and HAT were independent risk factors for early graft loss (within 3 months). The volume of intraoperative blood transfusion and the duration of anhepatic phase were independent risk factors for recipient death. Conclusions:Living donor liver transplantation is more effective than whole liver transplantation for children with low body weight (≤6 kg). Due to the small sample size and the early exploration stage of split liver transplantation in children, the efficacy of split liver transplantation remains to be explored in clinical practice.

Risk factors of biliary complications after pediatric living donor liver transplantation / 中华器官移植杂志

Objective:To explore the risk factors of biliary complications(BCS)after pediatric living donor liver transplantation(LDLT).Methods:From January 2016 to December 2020, retrospective review of clinical data was performed for 681 children aged <18 years undergoing LDLT.There were 324 boys and 357 girls with a median age of 7.4 months and a median weight of 7.0 kg.Among 61 BCS patients(9.0%), there were biliary stricture(n=34, 5.0%), bile leakage(n=21, 3.1%)and bile leakage combined with biliary stricture(n=6, 0.9%). According to the absence or presence of BCS after LT, the recipients were divided into two groups of BCS(n=61)and non-BCS(n=620). The incidence and risk factors of BCS were analyzed.T-test, Wilcoxon rank sum test, Chi square or Fisher exact test was employed for univariate statistical analysis and Logistic regression for multivariate statistical analysis.Results:The median follow-up period was 35.5 months.Univariate analysis revealed statistically significant inter-group differences( P=0.005, 0.046, 0.009, 0.011, 0.024, 0.023, 0.004, 0.038, 0.002, 0.029, 0.023, 0.002, 0.011)in donor age[(31.4±5.7)vs.(34.3±7.5)years], time of anhepatic phase[43(37.0, 53.0)vs.47(38.8, 56.0)min], time from portal vein opening to hepatic artery opening[35(30.0, 41.0)vs. 38(30.8, 47.8)min], type of perfusion fluid, number of donor bile ducts, intestinal loop length[40(30.0, 40.0)vs.40(25.0, 40.0)cm], mode of biliary reconstruction, whether or not placing a support tube, incidence of hepatic artery thrombosis[1.6%(10/620)vs.9.8%(6/61)], incidence of abdominal infection[4.5%(28/620)vs.11.5%(7/61)], incidence of cytomegalovirus(CMV)infection[55.3%(343/620)vs.70.5%(43/61)], incidence of portal vein thrombosis[1.1%(7/620)vs.8.2%(5/61)]and incidence of pulmonary infection[19.0%(118/620)vs.32.8%(20/61)]. Multivariate analysis indicated that independent risk factors of BCS included donor age( P=0.023), number of donor bile ducts( P=0.017), time from portal vein opening to hepatic artery opening( P=0.010), hepatic artery thrombosis( P=0.004), abdominal infection( P=0.019), CMV infection( P=0.022), portal vein thrombosis( P=0.003), pulmonary infection( P=0.021)and short intestinal loop length( P=0.012). Conclusions:Biliary complications are common after pediatric LDLT.Independent risk factors are donor age, number of donor bile ducts, time from portal vein opening to hepatic artery opening, hepatic artery thrombosis, abdominal infection, CMV infection, portal vein thrombosis, pulmonary infection and short length of intestinal loop.

The effects of naringenin on pancreatic fibrosis in chronic pancreatitis mouse model and activation, proliferation and apoptosis of pancreatic stellate cells / 中华胰腺病杂志

Objective:To study the effects of naringenin on pancreatic fibrosis in the mouse model of chronic pancreatitis (CP) and its effects on the activation, proliferation and apoptosis of pancreatic stellate cells (PSCs).Methods:Eighteen C57BL/6 mice were randomly divided into control group, CP group and naringenin group, with 6 mice in each group. The CP mouse model was established by intraperitoneal injections of caerulein. Naringenin group was given naringenin (200 mg/kg/day) by gavage once a day from the first day of the fourth week of modeling process to the day before the killing; the control group and CP group were treated by gavage with an equivalent amount of drug solvent containing 0.5% sodium carboxymethyl cellulose (CMC-Na). Mice were killed 5 days after the last caerulein injection, and their pancreatic tissues were collected for hematoxylin-eosin staining and Sirius Red staining, pathological scoring and collagen sedimentation detection. Naringenin with different concentrations (0, 5, 10, 20, 50, 100, 150, 200 μmol/L) were used to intervene HPSC for 24 hours, and CCK-8 method was used to detect the cell activity. TGF-β1 recombinant protein (2 ng/ml) was used to induce PSCs for 1 hour (TGF-β1 stimulation group), and naringenin with low (50 μmol/L), middle (100 μmol/L) and high (150 μmol/L) concentration was used to intervene for 36 hours after TGF-β1 stimulation, respectively. Western Blotting was used to detect the expression of PSC activation related proteins FN and COL1A1, cell proliferation marker p21, anti-apoptotic protein Bcl-xL, pro-apoptotic protein Bax and Bid.Results:The pathological scores of pancreatic tissue [(7.33±1.15), (4.67±1.15)] and the percentage of collagen positive areas [(46±4), (28±2)%] in CP group and naringenin group were higher than those in the control group [0, (4±2)%]. However, these indexes in the naringenin group were lower than those in CP group, and the differences were all statistically significant (all P value <0.05). The relative expression of FN in control group, TGF-β1 stimulation group and low, medium and high naringenin group was 0.02, 0.76, 0.67, 0.34 and 0.07, respectively; the expression of COL1A1 in these groups was 0.51, 1.71, 1.34, 0.84 and 0.11. The expression of FN and COL1A1 in TGF-β1 stimulation group was significantly higher than that in control group, and the expression of FN and COL1A1 in low, medium and high naringenin group was significantly lower than that in TGF-β1 stimulation group, and the differences were all statistically significant (all P value <0.05). The expression of p21 in the above five groups was 0.87, 1.18, 1.27, 1.22 and 1.00. The expression of p21 in TGF-β1 stimulation group was higher than that in control group, and the expression of p21 in high naringenin group was obviously lower than that in TGF-β1 stimulation group, and the differences were all statistically significant (all P value <0.05). In addition, the expression of Bcl-xL in these groups was 2.09, 2.21, 2.38, 2.50 and 2.12; the expression of Bax was 0.98, 0.88, 0.98, 1.00 and 0.88; the expression of Bid was 1.15, 1.09, 1.14, 1.18 and 1.18. There was no statistically significant difference among these groups (all P value >0.05). Conclusions:Naringenin could significantly alleviate the inflammation, atrophy and fibrosis in the CP mouse model, and inhibit the activation and proliferation of PSCs. However, naringenin had no significant effect on the apoptosis of PSCs, indicating that naringenin may be potentially used to treat pancreatic fibrosis in CP.

Clinical information analysis of 10 533 patients of chronic pancreatitis-summary of clinical treatment in Changhai Hospital over 28 years / 中华胰腺病杂志

Objective:To summarize the experience of treatment for chronic pancreatitis by analyzing the clinical information of 10 533 patients with chronic pancreatitis admitted to First Affiliated Hospital of Naval Medical University (Changhai Hospital) in the past 28 years.Methods:Clinical data including the age, sex, place of birth, admission time, admission age, admission department, discharge time, hospitalization times and treatment methods of chronic pancreatitis patients admitted to Changhai Hospital from January 1995 to February 2022 were analyzed retrospectively. The changes of chronic pancreatitis patients′ admission, demographic characteristics and treatment mode were summarized.Results:A total of 10 533 patients were analyzed, including 7 443 males (70.66%) and 3 090 females (29.34%), and male to female ratio was 2.41∶1. The average age of admission was (45.7±15.0) years. In terms of geographical distribution, East China was the largest, followed by North China and Northwest China. 10 533 patients were admitted for 19 920 times, and there were 18 156 times (91.14%) in gastroenterology department and 1 452 times (7.29%) in general surgery department. Patients in gastroenterology department were admitted for (1.88±1.45) times and the average length of hospitalization was (10.33±5.63) days. A total of 14 134 endoscopic retrograde cholangiopancreatography [(1.45±1.41) times per patient] were performed among 8 022 patients, and 13 882 pancreatic extracorporeal shock wave lithotripsy [(2.22±0.36) times per patient] were performed among 6 629 patients. In general surgery department, patients were admitted for (1.03±0.16) times and the average length of hospitalization was (14.90±9.00) days. 1 242 patients underwent surgical treatment. The ratio of endoscopic therapy to surgery increased from 0.12∶1 in 1995 to 15.72∶1 in 2021.Conclusions:The study shows that chronic pancreatitis was more common in middle-aged males in China, and the treatment modes of chronic pancreatitis in Changhai Hospital had changed from surgery to endoscopic therapy.

Application research of multiple intelligences theory combined with the ADDIE model in surgical clinical practice teaching / 中华医学教育探索杂志

Objective:To explore the effect of multiple intelligences theory combined with the analysis, design, development, implementation, and evaluation (ADDIE) model in surgical clinical practice teaching.Methods:A total of 100 residents trained in Department of Gastrointestinal Surgery of Heping Hospital Affiliated to Changzhi Medical College from July 2019 to April 2020 were randomly divided into the control group ( n=50) and the observation group ( n=50). The control group used the ADDIE model, and the observation group adopted the multiple intelligences theory combined with the ADDIE model. The teaching assessment of the two groups was compared, and the core competence, critical thinking ability, self-evaluation, and teaching satisfaction of the two groups were evaluated. SPSS 22.0 was used for Chi-square test and t-test. Results:The scores of basic knowledges of gastrointestinal surgery, surgical clinical thinking and case analysis, routine skills and operations, and the total scores in the observation group were higher than those in the control group ( P<0.05). The scores of professional knowledge and skills, patient safety and rights, scientific research and academic ability, professional ethics, teamwork, personal and professional development ability in the observation group were higher than those in the control group ( P<0.05). While, there was no significant difference in the mastering of knowledge between the two groups ( P>0.05). The four dimensions of learning interest, self-learning ability, innovation ability, and clinical thinking establishment in the observation group were higher than those in the control group ( P<0.05). Conclusion:Multiple intelligences theory combined with ADDIE model in surgical clinical practice teaching can improve the teaching assessment results, significantly enhance the core competence, stimulate the learning interest, cultivate the self-learning ability and innovation ability of residents, and help them to establish clinical thinking ability.

Impact of left hepatic vein classification on hepatic vein reconstruction and prognosis after pediatric living-donor liver transplantation using left lateral liver segments / 中华肝胆外科杂志

Objective:To study the impact of donor left hepatic vein classification and the reconstruction methods on hepatic venous outflow obstruction (HVOO) after pediatric living-donor liver transplantation using left lateral liver segments.Methods:A retrospective study was performed on the clinical data of 653 children recipients who underwent living-donor liver transplantation with left lateral liver segments from January 2014 to December 2020 at Tianjin First Central Hospital. There were 309 males and 344 females, aged 7.0 (6.0, 10.0) months, with an age range of 3-121 months. Based on the left hepatic vein on preoperative donor enhancement CT as well as the intraoperative reconstruction methods, the recipients were divided into 3 groups: type Ⅰ group ( n=514), anastomosis using a single opening was performed directly between the donor and the recipient; type Ⅱ group ( n=118), angioplasty was performed on two adjacent recipient venous orifices before anastomosis, and type Ⅲ group ( n=21), an interposition vessel was anastomosed to two widely spaced openings or the two veins were anastomosed separately. The preoperative general status of the patient, postoperative HVOO incidences, and graft and recipient survival rates were compared among the three groups. The patients were followed up by outpatient reexamination or telephone. Results:Graft to recipient weight ratio in the type Ⅲ group was smaller than that in the type Ⅰ group and the type Ⅱ group ( P<0.05). For all the 653 patients, the incidence of postoperative HVOO was 4.59% (30/653), with the incidences of HVOO in the 3 groups of patients were 4.1% for the type Ⅰ group (21/514), 5.1% for the type Ⅱ group (6/118), and 14.3% for the type Ⅲ group (3/21), respectively. There was no significant difference among the groups ( P>0.05). The recipient cumulative survival rates at 1 and 3 years after surgery in the type I group were 97.8% and 97.0%, and the corresponding rates in the type Ⅱ group were 96.5% and 94.2%, and in the type Ⅲ group were 94.1% and 86.9%, respectively. There was a significant difference between the type Ⅰ and type Ⅲ groups ( P=0.048). The graft cumulative survival rates at 1 and 3 years in the type Ⅰ group were 97.4% and 96.9%, and the corresponding rates in the type Ⅱ group were 94.9% and 92.5%, and in the type Ⅲ group were 94.1% and 86.9%, respectively. The difference in the postoperative graft cumulative survival rates between the type Ⅰ group and type Ⅱ group was significant ( P=0.044). Conclusions:The anatomy of the left hepatic vein supplying the left lateral liver segment was highly variable, and the majority of the variations could be reconstructed. A reasonable reconstructive method could reduce the incidence of postoperative HVOO and improved the outcomes of the graft.

Impact of graft/recipient weight ratio on the prognosis of infants with whole liver transplantation / 中华器官移植杂志

Objective:To explore the impact of graft recipient weight ratio(GRWR)on pediatric whole liver transplantation in infants aged under 1 year.Methods:From January 2014 to December 2019, clinical data were retrospectively reviewed for 140 children aged under 1 year with whole liver transplantation.They were divided into 3 groups of low GRWR(GRWR<2.5%, 48 cases), middle GRWR(2.5%≤GRWR<5%, 73 cases)and high GRWR(GRWR≥5%, 19 cases). Basic profiles, major postoperative complications and survival rate of graft/recipient were compared.Results:There were 62 males and 78 females with an average age of (7.34±1.81)months and an average weight of(6.81±1.09)kg.The median GRWR was 3.27%(1.33%~8.12%). The higher level of GRWR, the greater age, weight and graft weight of donor in three groups and there was statistical difference ( P<0.05); operative duration, postoperative ICU stay and hospital stay were longer in low GRWR group than those in middle GRWR group and there was statistical difference( P<0.05); The incidence of postoperative hepatic artery thrombosis was higher in low GRWR group than that in middle GRWR group(31.3%vs 8.2%)and there was statistical difference( P<0.05); 4 cases of small-for-size syndrome occurred in low GRWR group, it was significantly different from the other two groups and there was statistical difference( P<0.05); the median follow-up period was(50.7±23.4)months.The survival rates of grafts at 3-month and 1/5-year were 89.6%, 91.8%, 100%; 87.5%, 87.7%, 100%; 87.5%, 87.7%, 100%and there was no inter-group difference( P>0.05). The survival rates of recipients at 3 months, 1 year and 5 years post-operation were 93.8%, 91.8%, 100%; 91.7%, 87.7%, 100%; 91.7%, 87.7%, 100%and there was no inter-group difference( P>0.05). Conclusions:Different from pediatric living donor transplantation, GRWR≥5%does not affect the survival rate of recipient/graft during whole liver transplantation.And GRWR<2.5%may boost the postoperative incidence of hepatic artery thrombosis and small liver syndrome.

Promising natural lysine specific demethylase 1 inhibitors for cancer treatment: advances and outlooks / 中国天然药物

Lysine specific demethylase 1 (LSD1), a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9, has become a potential therapeutic target for cancer therapy. LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation, invasion, migration, and differentiation. Recent research has focused on the exploration of its pharmacological inhibitors. Natural products are a major source of compounds with abundant scaffold diversity and structural complexity, which have made a major contribution to drug discovery, particularly anticancer agents. In this review, we briefly highlight recent advances in natural LSD1 inhibitors over the past decade. We present a comprehensive review on their discovery and identification process, natural plant sources, chemical structures, anticancer effects, and structure-activity relationships, and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.

Identification of a novel PHGDH covalent inhibitor by chemical proteomics and phenotypic profiling

The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.