BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.

Objective:To evaluate the short-term and long-term efficacy of Heidelberg triangle dissection in surgical treatment for pancreatic head cancer.Methods:The clinicopathological data of 97 patients with pancreatic head cancer who underwent pancreaticoduodenectomy at Cangzhou Central Hospital from Jan 2017 to Jan 2020 were retrospectively analyzed. After propensity score matching, 33 patients were included into the Heidelberg group and 36 patients in the control group.Results:There were no significant difference between Heidelberg group and control group in preoperative general conditions and postoperative major complications, while there were more cases with safe surgical margin > 1 mm (81.8% vs. 58.3%, P=0.034) and a significantly higher total number of lymph node dissection (11.24±2.35 vs. 9.50±2.76, P=0.006). In the survival analysis, the cumulative recurrence rate at 12 months (0.182±0.067 vs. 0.444±0.083, P=0.023) and 18 months (0.424±0.086 vs. 0.667±0.079, P=0.024) were better off in the Heidelberg group, and the local recurrence rate in the Heidelberg group was significantly lower than that in the control group (15.3 % vs. 36.1 %, P=0.037). However, there was no statistical difference in the overall survival time between the two groups. Conclusion:Dissection of Heidelberg triangle in radical resection of pancreatic head cancer reduces tumor local recurrence ,while fails to provide survival benefit.

Objective:Exploring the effect of radiofrequency ablation treatment to restore sinus rhythm on the improvement of functional mitral regurgitation (FMR) and cardiac structure in patients with atrial fibrillation combined with moderate or severe FMR, compared with drug therapy alone.Methods:This retrospective cohort study consecutively enrolled patients diagnosed with persistent atrial fibrillation and moderate or severe FMR who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2021. Forty-eight patients who were treated with radiofrequency ablation and maintained sinus rhythm were enrolled in the ablation group, and 63 patients who were treated with medication alone during the same period were in the medicine group. Patients in the ablation group and medicine group were matched in a 1∶1 ratio using a propensity score, and 41 patients were finally included in each of the 2 groups. All patients reexamined echocardiography after 3-month of treatment. The proportion of patients with FMR improvement and the differences in changes of cardiac structural and functional parameters were compared between groups.Results:After propensity score matching, the ablation group was aged (69.3±7.1) years with 21 males (51.2%) and the medicine group was aged (71.3±9.4) years with 21 males (51.2%). The echocardiography after 3-month of treatment showed the rate of FMR improvement was significantly higher in the ablation group than in the medicine group (19 (46.3%) vs. 33 (80.5%), P<0.001), and patients in the ablation group showed a significant decrease in FMR extent (Δmitral regurgitation area: (-1.30±2.64) cm 2 vs. (-3.55±2.50) cm 2, P<0.001), left atrial size (Δleft atrial diameter: (-0.17±3.78) mm vs. (-2.46±4.01) mm, P=0.009) and E/e′ (ΔE/e′:-2.54±7.34 vs.-6.34±7.08, P=0.021) compared with the medicine group. There was also a significant decrease in left ventricular size (Δleft ventricular end diastolic diameter: (-3.12±6.62) mm vs. (-0.73±3.62) mm, P=0.046) and significant increase in left ventricular ejection fraction (Δleft ventricular ejection fraction: (2.73±9.69) % vs. (-0.93±5.41) %, P=0.038) in ablation group. Conclusion:Performing radiofrequency ablation to restore sinus rhythm can effectively reduce the severity of mitral regurgitation and improve left atrial and left ventricular remodeling and cardiac function in patients with atrial fibrillation and FMR.

Objective:To investigate the expression of programmed cell death protein 1 (PD-1), programmed cell death ligand 1(PD-L1), and lymphocyte-activation gene 3(LAG-3) in different subsets of lymphocytes and their relationship with the immunologic imbalance in preeclampsia.Methods:We enrolled 25 cases of singleton pregnant women with preeclampsia who were delivered by cesarean section in the Shandong Provincial Hospital Affiliated to Shandong First Medical University from May 2019 to January 2020 as the preeclampsia group. According to the allocation ratio of 1∶1 matched for the date of cesarean section and pregnancy week at delivery, another 25 healthy singleton pregnant women underwent elective cesarean section were selected as the normal group. The decidua tissue was obtained during cesarean section. The expression levels of PD-1, PD-L1, and LAG-3 on decidual T cells, natural killer (NK), and natural killer T (NKT) cells were measured by flow cytometry and compared between the two groups using two independent samples- t test. Results:(1) The expression of PD-1 on decidual T cells and NK cells of the preeclampsia group were lower than those of the normal group (37.84±3.82 vs 57.02±3.89, t=3.529, P<0.001; 3.28±0.48 vs 5.69±0.99, t=2.184, P=0.034), but did not differ significantly in the expression on decidual NKT cells ( P=0.461). PD-L1 expression on decidual NK cells of preeclampsia group was lower than that of the normal group (0.60±0.11 vs 1.32±0.19, t=3.319, P=0.002), but showed no significant difference in the expression level on T cells and NKT cells (both P>0.05). The preeclampsia group was noted for a lower expression of LAG-3 on decidual T cells and NKT cells compared with the normal group (2.32±0.36 vs 4.09±0.67, t=2.335, P=0.024; 35.40±4.97 vs 56.27±4.49, t=3.282, P=0.002), while showed no significant difference in the expression level of NK cells ( P=0.112). Conclusions:The decreased expression of PD-1, PD-L1, and LAG-3 in the decidual lymphocyte subsets may be involved in the immunologic imbalance of preeclampsia through the over-activation of immunocytes at the maternal-fetal interface.

Objective:To investigate the clinical effects of lacunar closure-assisted internal fixation in the one-stage treatment of Morel-Lavallée injury complicated with pelvic fracture.Methods:The 32 patients were retrospectively analyzed who had been treated for Morel-Lavallée injury complicated with pelvic fracture at Department of Orthopedic Trauma, Honghui Hospital Affiliated to Xi'an Jiaotong University from May 2018 to November 2020. They were 21 males and 11 females, aged from 18 to 58 years (average, 40.5 years). The injury was located at a unilateral hip in 20 cases, at bilateral hips in 6 cases, at low back in 4 cases, and at posterior thigh in 2 cases. The pelvic fractures were treated by open reduction and internal fixation while the Morel-Lavallée injuries by lacunar closure at the same time. Their wound healing, pelvic function and complications were observed regularly.Results:The hospital stay of 32 patients ranged from 14 to 28 days, averaging 19.2 days. The patients were followed up for 6 to 18 months (mean, 9.3 months). The area of Morel-Lavallée injury healed after one lacunar closure in 23 patients who obtained fine skin survival and no soft tissue necrosis or other complications; the wounds in the Morel-Lavallée injury area healed well after secondary lacunae closure in 4 patients. Superficial sensation of the skin decreased around the Morel-Lavallée injury area after wound healing in 3 patients. Wound fat liquefaction was found in the Morel-Lavallée injury area but responded to symptomatic treatment in one patient. A small amount of wound secretion found in the Morel-Lavallée injury area was cured also by symptomatic treatment in another patient whose bacterial culture was negative. All the fractures healed after 3 to 6 months (average, 3.9 months). At the last follow-up, the Majeed scores for the pelvic function ranged from 65 to 100 points, averaging 84.5 points.Conclusion:For Morel-Lavallée injury complicated with pelvic fracture, lacunar closure-assisted internal fixation can result in a satisfactory one-stage treatment.

Objective To assess the effect of preoperative administration of tranexamic acid (TXA) on the hidden blood loss in the surgery of intertrochanteric fractures with proximal femoral nail anti-rotation (PFNA).Methods Eighty patients with intertrochanteric fracture were treated with PFNA in our hospital from November 2015 to July 2016.They were 15 men and 65 women,with a mean age of 72.6 years.Of them,39 were included into TXA group where TXA was administered preoperatively and 41 were assigned into the control group where no TXA was used preoperatively.Blood routine examinations were carried out on one day before operation,the first and third days after operation.The surgical blood loss,operative blood transfusion,24-hour drainage after operation,and postoperative 3-day blood transfusion were recorded.The total and hidden blood losses were calculated according to the formula.The 2 groups were compared in terms of blood loss and complications.Results In TXA group,the total blood loss (1,632.3 ± 849.2 mL),the hidden blood loss (1,270.9 ± 623.3 mL) and the transfusion rate (28.2％) were significantly lower than those in the control group (2,014.8 ± 924.7 mL,1,549.1 ± 624.9 mL and 56.1％) (P ＜ 0.05).There was no significant difference between the 2 groups in visible blood loss (361.4 ± 154.3 mL for TXA group versus 465.7 ± 191.3 mL for the control group) (P ＞ 0.05).Deep venous thrombosis occurred in 2 patients,limb swelling in one patient and wound dehiscence in one patient in TXA group while deep venous thrombosis occurred in one patient,limb swelling in 3 patients and wound dehiscence in none in the control group,showing no significant differences between the 2 groups (P ＞ 0.05).No infection was observed in either group.Conclusion Preoperative administration of TXA can reduce surgical hidden blood loss and transfusion rate as well but will not increase the risk of deep vein thrombosis in the surgery of intertrochanteric fractures with PFNA.

Objective To analyze the difference of laboratory test results between early-onset and late-onset severe preeclampsia and to investigate their clinical application values.Methods Totally 108 blood samples were collected from patients with severe preeclampsia who were diagnosed according to the Diagnostic Standard of Obstetrics and Gynecology(7th Edition) published by People′s Medical Publishing House,in Shandong Provincial Hospital affiliated to Shandong University from March to November 2016,which consisted of 64 early-onset severe preeclampsia before 34 weeks gestation(early onset group) and 44 late-onset severe preeclampsia after 34 weeks gestation(late onset group).In addition,42 women with normal pregnancies as the control group were selected.General clinical data were collected,and the blood sample was analyzed through detecting Hb,PLT,fibrinogen (FIB),D-dimer,AST,ALT,urea,creatinine (Cr),uric acid,CRP,urine protein.The tested results were analyzed and compared.Flow cytometry was used to analyze the proportion of T helper 1 cells(Th1) and T helper 2 cells(Th2),and the ratio of Th1/Th2 was also calculated.All data and F test were performed by use of statistical software SPSS19.0.Results The pre-pregnancy body mass index(29.55±4.49,30.66±5.13,26.62±3.17,F=9.829,P<0.05),diastolic blood pressure[(105.17±14.46)mmHg(1 mmHg=0.133 kPa),(99.80±12.56)mmHg,(74.36±8.42)mmHg,F=82.088,P<0.05],Hb[(123.22±14.38)g/L,(117.03±16.48)g/L,(112.62±11.24)g/L,F=7.133,P<0.05],urea[(6.56±2.36)mmol/L,(4.51±1.35)mmol/L,(3.04±0.87)mmol/L,F=51.733,P<0.05],Cr[(68.47±18.05)μmol/L,(61.37±14.37)μmol/L,(48.54±8.73)μmol/L,F=23.737,P<0.05],CRP[(7.68±8.76)mg/L,(5.88±6.03)mg/L,(3.56±2.41)mg/L,F=4.735,P<0.05],urine protein[(3.66±0.76)g/L,(2.20±1.05)g/L,(0.19±0.40)g/L,F=249.714,P<0.05]had a statistically significant difference among the early-onset,late-onset and control groups.The flow cytometry results demonstrated that the proportion of Th1 in early-onset group(19.83±3.04)was higher than that in both late-onset (14.49±2.79)and control groups(11.78±1.17),on the contrary,the result of Th2 was much lower(early-onset:1.02±0.12,late-onset: 1.11±0.12,control: 1.56±0.11),there was statistical significance among these three groups(Th1: F=135.110,P<0.05;Th2: F=293.687,P<0.05).Conclusions It′s necessary to real-time monitor the laboratory indicators,such as liver and kidney function,especially the immunologic function indicators for evaluating the disease of early-onset and late-onset severe preeclampsia and personal treatment,and for ensuring the health of mother and fetus and improving the prognostic of mother and fetus.

Objective To study the clinical effects of methylenetetrahydrofolate reductase(MTHFR) C677T gene mutation on mild vascular cognitive impairment(VCI)in patients with cerebral infarction.Methods The prospective study was conducted in 180 patients with atherosclerotic acute cerebral infarction hospitalized from June 2015 to May 2016.180 patients were divided into normal homocysteine(Hcy)group (Hcy 5.46～16.20 μmol / L,n=130)and high Hcy group(Hcy＞16.20 μmol / L,n=50).MTHFR C677T genotypes were detected by polymerase chain reaction-restriction endonuclease fragment length polymorphism.The VCI state and risk factors for VCI were analyzed with Montreal Cognitive Assessment scale(MoCA)and Mini Mental State Examination(MMSE)score in patients with acute cerebral infarction on admission and 14 days,30 days and 90 days after admission.Results MMSE and MoCA scores at 14 days,30 days,90 days after admission were lower in high Hcy group than in normal Hcy group(P＜0.05 or P＜0.01).MMSE and MoCA scores were lower in T/T genotype than in C/C genotype(P＜0.05)at 14 day after admission,and lower in C/T genotype than in C/C genotype at 30 day and 90 day follow up(P＜0.05or P＜0.01).Logistic regression analysis showed that Hcy may be independent risk factors for mild VCI(OR =1.274,95％CI:1.027～1.264,P=0.018).Conclusions MTHFR C677T gene mutations may cause hyper-homocysteinemia,and promote the emergence of VCI in patients with cerebral infarction.MTHFR C677T gene mutations may be a genetic susceptibility factor for VCL

Objective To evaluate the clinical outcomes in patients with both column acetabular fractures involvement posterior wall using lag screw through single ilioinguinal approach.Methods Between August 2008 to August 2014,35 consecutive patients with both columns acetabular fractures and fracture also involved posterior wall and fixed by lag screws were retrospectively analyzed.There were 25 males and 10 females.The average age was 44.4+ 12.5 years (range,18-72 years).According to Letournel classifications,the acetabular fracture involved both columns and posterior wall in all cases,and 2 cases with additional seagull sign.The surgeon reduced posterior wall by pressing the fragment through a small tunnel in the soft tissue leaning against the external cortex of iliac bone and fixed the fragment using lag screws from the anterior side.Clinical and functional outcomes were assessed using the modified Merle d'Aubigné scoring system.Radiographic results were evaluated based on Matta scoring system.Results The patients were follow for an average of 44.7+ 18.9 months (range,24-96 months).The average operative time was 257.7±60.4 min (range,160-490 min).The average blood loss during the operating was 742.9±+614.5 ml (range,300-4 000 ml).Loss of reduction of the posterior wall was not found in any case.At the latest follow-up,radiographic results were excellent in 11,good in 19,and poor in 5.The average modified Merle d'Aubigné score was 16.4 (range,13-18).There were 8 cases of excellent,23 cases of good,and 4 cases of fair.Four patients developed deep venous thrombosis of the lower extremities after 3-4 days of operation.Warfarin was used for anticoagulation therapy and thrombi disappeared 6 months postoperatively.One case had superficial wound infection and was treat with vacuum sealed drainage (VSD) and anti-infection therapy.The incision healed without infection after one month.One case with poor quality of reduction and remaining seagull sign was treated with total hip arthroplasty after 35 months because of severe traumatic arthritis.The total reoperation rate was 5.7％ (2/35).latrogenic sciatic nerve injury as well as heterotopic ossification was not found in any case.Conclusion Satisfactory quality of reduction and good clinical outcomes can be achieved in patients with acetabular fractures involved both columns and posterior wall by single ilioinguinal approach and lag screw fixation for posterior wall.Iatrogenic sciatic nerve injury as well as heterotopic ossification was not found in any case.

Kinesin spindle protein ( KSP) inhibitors is an important direction for the discovery of anticancer agents. Several KSP in-hibitors have been studied in clinic trials. The discovery of ATP-competitive KSP inhibitors may be a new approach for searching novel a-gents to overcome the mutation-mediated resistance to the allosteric inhibitors. The progress in the discovery of ATP-competitive KSP in-hibitors was reviewed in the paper to provide reference for the further development of KSP inhibitors.