BACKGROUND:As a dominant breed pig in southwest China,the southern Yunnan small-ear pig has been widely used as an experimental animal in the basic research of other disciplines,but there are still no reports on its application in anterior cruciate ligament reconstruction. OBJECTIVE:To establish a large animal model of the southern Yunnan small-ear pig with anterior cruciate ligament with autologous Achilles tendon was established. METHODS:Twenty adult female Yunnan small-ear pigs were equally randomized into two groups.In the autologous Achilles tendon group,the right knee anterior cruciate ligament was reconstructed with autologous Achilles tendon as a graft,while in the sham-operated group,a similar operation was performed on the right knee without any treatment of the anterior cruciate ligament.General conditions of each pig were observed and recorded before and 12 months after surgery.Ligaments and grafts were taken for gross observation and MAS scoring.Hematoxylin-eosin staining was performed to observe morphological characteristics of ligaments.The staining and arrangement of type I and type Ⅲ collagen were evaluated by immunohistochemistry.Transmission electron microscopy was used to observe the type,size,diameter,ratio,and distribution of collagen fibers in ligaments. RESULTS AND CONCLUSION:All animals had normal diet and activity,good wound healing,no obvious inflammatory reaction,no local purulent infection,and no significant changes in mental and urinary conditions compared with those before surgery.The reconstructed cruciate ligament of the knee was intact,with no stiffness and normal range of motion.Both the anterior drawer and Lachman tests were negative.Gross observation of the graft:12 months after surgery,the grafts was in good position,with good integrity,obvious tension,ligament color close to the original anterior cruciate ligament,and complete surface synovial coverage.Most of the intraarticular ligaments in the autologous Achilles tendon group were defined as MAS I type and a few were defined as MAS Ⅱ type.In the sham-operated group,the intraarticular ligament was defined as MAS I type.Hematoxylin-eosin staining indicated that,12 months after surgery,collagen fibers in the autologous Achilles tendon group began to appear bundled,isotropic,and uniformly arranged,with more obvious isotropic corrugations,and the nuclei were mainly linear or spindle-shaped,which were similar to those in normal anterior cruciate ligament tissue of the sham-operated group.Immunohistochemistry results indicated that,12 months after surgery,there was a higher expression of type I collagen and significantly less expression of type Ⅲ collagen in the reconstructed anterior cruciate ligament in the autologous Achilles tendon group.The degree of type I and type Ⅲ staining was similar in the two groups.Under the transmission electron microscope,the diameter,arrangement and density of collagen fibers in the reconstructed anterior cruciate ligament of the autologous Achilles tendon group were similar to those of the original anterior cruciate ligament at 12 months after surgery,indicating that the ligament remodeling process had been basically completed in the autologous Achilles tendon group at 12 months after surgery.Through a comprehensive evaluation of animal general conditions,ligament general view,MAS score,hematoxylin-eosin staining,immunohistochemistry,and transmission electron microscopy observation,we successfully established a large animal model of anterior cruciate ligament reconstruction using autogenous Achilles tendon in southern Yunnan small-ear pigs,with good morphological,histological and ultrastructural results.

Objective:To investigate the risk factors of invasive fungal disease after haploid hematopoietic stem cell transplantation in children with acute leukemia.Methods:Four hundred and two children (median age 10 years) with acute leukemia, undergoing haplo-HSCT at this institutute from January 2016 to December 2020,were analyzed retrospectively according to the diagnosis criteria of IFD. The basic information and preoperative indicators of the children were collected, including gender, age, primary disease, remission status of primary disease, and previous IFD history. Postoperative indicators were collected, including long-term granulocyte deficiency time, high-dose glucocorticoids, using CD25 monoclonal antibody, acute and chronic graft-versus-host disease. Count data are expressed as example (%), and comparisons between groups are made using the continuously multifactorial corrected Chi-square test or Fisher exact probability method. Logistic regression model was used to analyze the risk factors of IFD after haplo-HSCT in children.Results:Among 402 cases, 250 were male and 152 were female. The median age at transplantation was 10 years, and the age range was 9 months to 17 years 7 months. Before transplantation, 390 cases achieved complete remission of the primary disease, 9 cases had partial remission, and 3 cases had no remission. The implantation time of neutrophils ranged from +10 to 24 days, with a median time of 12 days. IFD occurred in 17 cases (4.2%), of which 3 cases (0.7%) were proven IFD and 14 cases (3.5%) were probable IFD. IFD occurred from 13 to 275 days after transplantation, with a median time of 30 days. The lungs were the most common site of infection (88.2%,15/17). The multivariate Logistic regression analysis showed that age >10 years old ( P=0.046, odds ratio =3.05, 95% confidence interval: 1.02~9.13), the use of high-dose corticosteroids ( P=0.005, odds ratio =7.72, 95% confidence interval: 1.85~32.20) were risk factors for IFD after haplo-HSCT in children. Conclusions:IFD is an important complication after haplo-HSCT in children with acute leukemia. Age >10 years and the use of high-dose corticosteroid are risk factors for IFD after haplo-HSCT in children with acute leukemia.

Objective:To investigate the efficacy and safety of different transcatheter arterial chemoembolization(TACE)-based regimens in patients with unresectable hepatocellular carcinoma(uHCC)and explore the optimal timing for combining TACE with tyrosine kinase inhibit-ors(TKIs)and immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital,Southern Medical University.The pa-tients were assigned into the following four groups according to different treatment regimens:TACE group(n=317),TACE combined with TKIs group(TACE+TKIs,n=66),TACE combined with ICIs group(TACE+ICIs,n=33),and TACE combined with TKIs+ICIs group(TACE+TKIs+ICIs,n=139).Subgroup analysis was performed within the TACE+TKIs+ICIs group,with patients being assigned into"pre-TACE"and"post-TACE"groups based on the timing of the combination therapy.Univariate and multivariate Cox regression analyses were conducted to identify pro-gnostic factors influencing overall survival(OS).Results:The TACE+TKIs+ICIs group showed the longest OS(21.9 months,95%confidence in-terval[CI]:17.2-26.6,P=0.030)and progression-free survival(PFS)(8.3 months,95%CI:7.3-9.3,P=0.004)compared to those in the other three groups.In the subgroup analysis,the"post-TACE"group had longer OS than the"pre-TACE"group(26.8 months vs.19.2 months,P = 0.011).The objective response rate(ORR)was 32.8%,41.1%,42.4%,and 52.5%(P=0.001)and the disease control rate(DCR)was 59.6%,71.2%,69.7%,and 82.7%(P<0.001)in the TACE,TACE+TKIs,TACE+ICIs,and TACE+TKIs+ICIs groups,respectively.The adverse events were similar to those reported in previous studies.Cox regression analysis revealed that tumor number,extrahepatic metastasis,and treatment regimen were independent factors influencing OS in patients(all P<0.05).Conclusions:TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE,and the combination of TKIs+ICIs with TACE achieves better beneficial outcomes.The greatest OS was observed when the combination therapy TKIs+ICIs was initiated within 3 months after the first TACE procedure.

Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.

Objective:To evaluate the value of time-signal intensity curve (TIC) combined with apparent diffusion coefficient (ADC) obtained with 1.5T magnetic resonance imaging in the evaluation of anal fistula activity.Methods:The clinical, imaging, and pathological data of 71 patients with pathologically confirmed anal fistula who received treatment in Ningbo Yinzhou No.2 Hospital from June 2018 to February 2020 were retrospectively analyzed. These patients were divided into active phase group ( n = 42) and remission phase group ( n = 29) according to surgical findings and pathological tissue composition. Pearson's chi-square test was used to analyze TIC types. The ADC value was compared between the two groups. Results:TIC types: In the active phase group, the percentage of patients with type I curve (rising enhancement pattern) and type III curve (washout pattern) was 47.6% (20/42) and 35.7% (15/42) respectively, which were significantly higher than that of patients with type III curve [plateau pattern; 16.7% (7/42)], χ2 = 9.22, 3.94, both P < 0.05). In the remission phase group, the percentage of patients with type I and II curves was 34.5% (10/29) and 55.2% (16/29) respectively, which were significantly higher than that of patients with type III curve [10.3% (3/29), χ2 = 4.86, 13.23, both P < 0.05]. ADC value: ADC value in the active phase group was significantly lower than that in the remission phase group [(0.932 ± 0.074) × 10 -3 mm 2/s vs. (1.164 ± 0.061) × 10 -3 mm 2/s, t = -13.87, P < 0.001). Conclusion:TIC combined with ADC value can effectively evaluate anal fistula activity. It can be used as a routine method for preoperative evaluation and postoperative follow-up for patients with anal fistula.

Objective:To evaluate and analyze the methodology and quality of recommendations in clinical practice guidelines for frail elderly people.Methods:We systematically searched 4 databases including the PubMed, China National Knowledge Infrastructure (CNKI) , China Biology Medicine Database, Wanfang Data, as well as 5 guideline websites involving Guidelines International Network, Canadian Medical Association Clinical Practice Guideline, Scottish Intercollegiate Guidelines Network, National Institute for Health and Care Excellence, New Zealand Guidelines Group, and supplemented to search Medlive. The Appraisal of Guidelines for Research and EvaluationⅡ (AGREEⅡ) and the Appraisal of Guidelines for Research and Evaluation-Recommendation Excellence (AGREE-REX) were used to evaluate the overall quality of the included guidelines and the quality of the recommendations respectively.Results:A total of 862 documents were retrieved, and 5 guidelines were finally included after screening. Among the overall scoring results of the guideline, there were 4 articles in Grade B and 1 article in Grade C. The average scores of 6 fields in AGREEⅡ were scope and purpose 82.2%, stakeholder involvement 54.5%, rigor of development 38.7%, clarity of presentations 83.3%, applicability 30.8% and independence 21.1%. The average scores of 3 fields in AGREE-REX were clinical applicability 73.3%, values and preferences 20.8%, and implementability 65.0%. The guideline issued by the International Conference on Frailty and Sarcopenia Research in 2019 was of the highest quality.Conclusions:Most of the guidelines come from developed countries in Europe and America, and there are no clinical practice guidelines for frail elderly people in China. The newly released guidelines have improved the quality of the methodology and guideline recommendations, but the four fields of rigor, applicability, editorial independence, values and preferences need to be improved.

We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) (n = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group; 19.2% vs. 8.9%, P = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, P = 0.031) and disease-free survival (69.6% vs. 81.0%, P = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had Candida in their stool specimens.

Objective To estimate the value of diffusion tensor imaging (DTI) in early diagnosis of chronic allograft nephropathy (CAN) and monitoring of graft fibrosis in rat models . Methods Thirty CAN rat models were established as experimental group by transplanting Fisher donor kidneys into Lewis recipients. Thirty Lewis rats that received Lewis kidneys served as control group. Serum creatinine (SCr) was monitored regularly every two weeks from 14 days after transplantation. Eight rats were randomly selected by random number table method and underwent DTI examination at 4, 12, 20 weeks after modeling. DTI scans were performed on the renal cortex and medulla to measure apparent diffusion coefficient (ADC) and fractional anisotropy (FA). From the remaining 22 rats in each group, 6 rats were randomly selected and underwent pathological analysis at 4, 12, 20 weeks after modeling. Histological changes in the kidney were evaluated by chronic allograft damage index (CADI) scores. The expression of alpha-smooth muscle actin (α-SMA) and Vimentin were quantitatively measured. The differences in creatinine, DTI parameters, CADI score, α-SMA, Vimentin expression level were analyzed by two independent samples t test in two groups, the differences among CADI score, α-SMA, Vimentin expression level of the experimental group were compared using ANOVA. The correlations among DTI parameters and CADI score, α-SMA and Vimentin expression level were analyzed using Pearson analysis. Results The creatinine in the experimental group increased continuously, and the creatinine in the control group showed no significant increase. The difference in creatinine between the two groups was statistically significant from 8th week after operation (P＜0.01). There was no obvious difference in the size and signal intensity of transplanted kidneys in control group at different time points. Compared with the control group, the graft kidney in the experimental group at the 4 weeks demonstrated increased signal intensity with mild increased volume of kidney, and the boundaries between cortex and medulla were not clear. The cortex and medulla showed gradually increased signal intensity, heterogeneous signal distribution and marginal haziness over time. The ADC and FA value of renal cortex and medulla in experimental group were significantly lower than those in control group at 4, 12, 20 weeks (P＜0.05). The ADC and FA values of the cortex and medulla gradually decreased in the experimental group over time, while the values of the parameters in the control group did not show a significant decrease. The ADC and FA values of the cortex and medulla were negatively correlated with the scores of CADI, and the expression level of α-SMA, Vimentin in the experimental group(r=－0.50 to －0.85, P＜0.01).Conclusion DTI can be an effective technique for early diagnosis of CAN and monitoring of graft fibrosis process.

OBJECTIVE: To evaluate the safety and feasibility of neoadjuvant chemotherapy prior elective surgery following self-expanding metallic stents (SEMS) for complete obstructive left hemicolon cancer. METHODS: This prospective, multicenter, open-labelled trial was approved by the Ethics Committee of Beijing Chaoyang Hospital, Capital Medical University(2016-ke-161-1) and registered in Clinicaltrials.gov (NCT02972541). INCLUSION CRITERIA: (1)age between 18 and 75 years old;(2) adenocarcinoma confirmed by pathology;(3) left hemicolon cancer confirmed by clinical manifestations and imaging examinations with the distance to anal verge > 15 cm; (4) resectable cancer evaluated by imaging examination without distant metastasis; (5) Eastern Cooperative Oncology Group (ECOG) score ≤ 1 or Karnofsky Performance Scale (KPS) > 70, indicating tolerance of neoadjuvant chemotherapy and operation; (6) absence of chemotherapy or radiotherapy within past six months; (7) bone marrow system and hepatorenal function: hemoglobin ≥ 90 g/L, neutrophil ≥ 1.5×10/L, platelet ≥ 80×10/L, total bilirubin ≤ 1.5×ULN(upper limits of normal), serum transaminase ≤ 2.5×ULN, serum creatinine ≤ 1.0×ULN, endogenous creatinine clearance rate > 50 ml/min; (8) sign for informed consent. EXCLUSION CRITERIA: (1) multiple primary colorectal cancer; (2) rejection of operation;(3) presenting peritonitis or bowel perforation before SEMS; (4) unqualified conditions proved by inspector from registration data. According to inclusion criteria, 62 consecutive patients receiving neoadjuvant chemotherapy prior to elective surgery following SEMS for complete obstructive left hemicolon cancer from Beijing Chaoyang Hospital of Capital Medical University (n=31), Qilu Hospital of Shandong University (n=14), the Third Xiangya Hospital of Central South University (n=13), Zhongnan Hospital of Wuhan University (n=2), the Fourth Hospital of Hebei Medical University (n=2) between December 2015 and December 2017 were prospectively enrolled in this study. Patients were divided into neoadjuvant chemotherapy group and elective surgery group according to the investigator's clinical experience and patient's preference. Patients in the elective surgery group received surgery within one to two weeks after SEMS placement without neoadjuvant chemotherapy. Those in the neoadjuvant chemotherapy group received 2 cycles of CapeOX or 3 cycles of mFOLFOX6 neoadjuvant chemotherapy within one to two weeks after SEMS placement, and then underwent surgery within 3 weeks after finishing neoadjuvant chemotherapy. Data between groups were compared using Student t-test, chi-square analysis or Fisher exact test analysis, including basic clinical informations, operational conditions and postoperative complications. The adverse reactions during the neoadjuvant chemotherapy were recorded. Surgical difficulty was assessed using visual analog scales ranging from 1 to 10, where 1 represented the lowest and 10 the highest degree of surgical difficulty, as judged by the surgeon. RESULTS: The study included 38 males and 24 females with mean age of (64.8±8.8) years. The clinical baseline data between 2 groups were not significantly different (all P>0.05) except the average time interval between SEMS and surgery was significantly longer in neoadjuvant chemotherapy group [(61.6±13.5) days vs. (10.4±5.2) days, t=16.679, P<0.001]. There was no stent migration in either group. Three patients had perforation in the elective surgery group; one patient had perforation and one had obstruction in the neoadjuvant chemotherapy group; and all these patients received emergent surgery. Adverse reactions of neodajuvant chemotherapy were mainly degree 1 and 2 except one patient with degree 3 diarrhea. Patients in neoadjuvant chemotherapy group had significantly lower rate of stoma [4.8%(1/21) vs. 34.1%(14/41), χ²=6.538, P=0.011], higher rate of laparoscopic surgery [71.4%(15/21) vs. 36.6%(15/41), χ²=6.751, P=0.009], shorter mean operative time (147 minutes vs. 178 minutes, t=-3.255, P=0.002), less mean intraoperative blood loss (47 ml vs. 127 ml, t=-4.129, P<0.001), lower degree of surgical difficulty(3.3 vs. 5.6, t=-5.091, P<0.001), shorter mean postoperative exhausting time (56.2 hours vs. 69.0 hours, t=-2.891, P=0.006), and shorter mean postoperative hospital stay (8.5 days vs. 13.5 days, t=-2.246, P=0.028) as compared with patients in the elective surgery group. Surgical site infection rate and anastomotic leakage rate did not differ significantly between two groups(all P>0.05). CONCLUSION Neoadjuvant chemotherapy prior elective surgery following SEMS is a relatively safe and feasible approach in the treatment for obstructive left hemicolon cancer, and is associated with less stoma, more laparoscopic surgery, shorter operative time, less blood loss, lower surgical difficulty, and faster postoperative recovery as compared with conventional elective surgery.
Aged ; Colorectal Neoplasms ; surgery ; therapy ; Female ; Humans ; Intestinal Obstruction ; Male ; Middle Aged ; Neoadjuvant Therapy ; Prospective Studies ; Stents ; Treatment Outcome

In recent years , there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+LPD), and the name of EBV +LPD is used widely.However,the meaning of EBV+LPD used is not the same , which triggered confusion of the understanding and obstacles of the communication.In order to solve this problem.Literature was reviewed with combination of our cases to clarify the concept of EBV +LPD and to expound our understanding about it .In general, it is currently accepted that EBV +LPD refers to a spectrum of lymphoid tissue diseases with EBV infection , including hyperplasia , borderline lesions , and neoplastic diseases .According to this concept , EBV+LPD should not include infectious mononucleosis ( IM ) and severe acute EBV infection ( EBV +hemophagocytic lymphohistiocytosis, fatal IM, fulminant IM, fulminant T-cell LPD), and should not include the explicitly named EBV+lymphomas ( such as extranodal NK/T cell lymphoma , aggressive NK cell leukemia , Burkitt lymphoma, and Hodgkin lymphoma , etc.) either.EBV +LPD should currently include: ( 1 ) EBV +B cell-LPD:lymphomatoid granulomatosis , EBV +immunodeficiency related LPD , chronic active EBV infection-B cell type, senile EBV +LPD, etc.(2) EBV +T/NK cell-LPD:CAEBV-T/NK cell type, hydroa vacciniforme, hypersensitivity of mosquito bite, etc.In addition, EBV+LPD is classified, based on the disease process , pathological and molecular data , as 3 grades:grade1, hyperplasia ( polymorphic lesions with polyclonal cells ); grade 2, borderline ( polymorphic lesions with clonality ); grade 3, neoplasm (monomorphic lesions with clonality).There are overlaps between EBV +LPD and typical hyperplasia, as well as EBV+LPD and typical lymphomas .However , the most important tasks are clinical vigilance , early identification of potential severe complications , and treating the patients in a timely manner to avoid serious complications , as well as the active treatment to save lives when the complications happened .