Objective To summarize the diagnosis and treatment experience of portal vein aneurysm after liver transplantation. Methods Clinical data of two recipients with portal vein aneurysm after liver transplantation were retrospectively analyzed. Clinical features, diagnosis, treatment and prognosis were summarized based on literature review. Results Both two cases were diagnosed with intrahepatic portal vein aneurysm complicated with portal vein thrombosis and portal hypertension after liver transplantation. Case 1 was given with targeted conservative treatment and he refused to undergo liver retransplantation. Physical condition was worsened after discharge, and the patient eventually died from liver graft failure, kidney failure, lung infection, and septic shock. Case 2 received high-dose glucocorticoid pulse therapy, whereas liver function was not improved, and the patient was recovered successfully after secondary liver transplantation. Conclusions Long-term complication of portal vein aneurysm (especially intrahepatic type) after liver transplantation probably indicates poor prognosis. Correct understanding, intimate follow-up and active treatment should be conducted. Liver retransplantation may be a potential treatment regimen.

Objective:To design a method to introduce random six-dimensional setup error (6D-SE) into the intensity-modulated radiotherapy (IMRT) planning for rectal cancer and evaluate its dosimetric effect.Methods:A total of 21 IMRT plans for patients with rectal cancer were randomly selected as reference plans [2 Gy per fraction for a total of 50 Gy; a 5 mm uniform margin around the clinical target volume (CTV) was taken as the planning target volume (PTV)]. For each fraction of the reference plan, a randomly generated 6D-SE was introduced by adjusting the geometrical parameters of the radiation field, and the dose was recalculated. The overall dose distribution with 6D-SE was obtained by adding up the dose of each fraction. A treatment simulation program that could complete the above workflow was developed using the Varian Eclipse scripting API (ESAPI). 6D-SEs that obey two preset distributions [distribution 1: translational error obey N(0, 4 2), and rotational error obey N(0, 2 2); distribution 2: translational error obey N(0, 2 2), and rotational error obey N(0, 1 2)] were introduced into the reference plans, and the dosimetric effects were assessed. Results:When the reference plans, error distribution 1, and error distribution 2 were applied, the Dmin values of the CTV were (49.4±0.41), (47.56±0.76), and (49.17±0.64) Gy, respectively; the D98% values of the CTV were (50.23±0.07), (49.98±0.10), and (50.27±0.09) Gy, respectively; the D98% values of the primary target area (the kernel part of the target area, excluding the margins) were (50.25±0.08), (50.42±0.13), and (50.33±0.10) Gy, respectively; the D98% values of the marginal area were (50.22±0.10), (49.88±0.11), and (50.26±0.10) Gy, respectively. In addition, compared with the result of the reference plans, the result of errors 1 and 2 showed no significant changes in the mean dose of the bladder and femoral heads ( P>0.05), despite slight decreases in the conformity index of the dose distribution with limited clinical significance. Conclusion:The proposed method and the treatment simulation program developed thereupon can introduce the 6D-SE obeying different distributions into the IMRT plans for rectal cancer on demand and provide overall dosimetric changes.

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.
Humans ; Anti-Bacterial Agents/therapeutic use* ; China ; Drug Monitoring/methods* ; Polymyxin B ; Practice Guidelines as Topic

Objective:To investigate the serum levels of soluble growth stimulation expression gene 2 protein (sST2) and inflammatory factors in patients with acute left ventricular ejection fraction reduction heart failure (HFrEF) treated with sacubitril/valsartan.Methods:Ninety six patients with acute HFrEF admitted in The Affiliated Hospital of Qingdao University from March 2020 to March 2021 were enrolled. The patients were treated with sacubitril/valsartan,the dose was gradually increased from 50 mg b.i.d to the target dose of 200 mg b.i.d according to hemodynamics. After 12 weeks, the target dose was achieved in 72 cases (compliance group), and did not achieved in 24 cases (non-compliance group). The serum levels of sST2, IL-1β, IL-6, TNF-αand IL-10 were measured and compared between the two groups. The changes in left atrial anteroposterial diameter (LA), left ventricular end-diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) values were assessed with echocardiography. The adverse reactions, readmission rate and all-cause death within 3 months after discharge were compared between the two groups.Results:A total of 96 patients with acute HFrEF completed the follow-up, including 72 patients (75.0%) in the compliance group and 24 (25.0%) in the non-compliance group; aged 50-75 (66.1±6.7) years old, and 68 (70.8%) males. After treatment, the serum levels of sST2, IL-1β, IL-6 and TNF-α were decreased, and the IL-10 level was increased in both groups ( P<0.05); while the improvement of serum indicators in the compliance group was more marked ( P<0.05). Echocardiography showed that the LA, LVDd, and LVEF were significantly increased after treatment ( P<0.05) in compliance group, while there was no significant changes before and after treatment in the non-compliance group. SST2, inflammatory factors and echocardiographic measurements of patients in the standard group had statistical significance before and after treatment ( P<0.05), and the difference showed a downward trend. No deterioration of renal function and angioedema were observed in both groups, and there was no significant difference in hyperkalemia (two in compliance group and one in non-compliance group), symptom hypotension (each in two groups) between the two groups (χ 2=0.12, 0.68; P>0.05). In the non-compliance group, 10 patients (41.7%) were readmitted due to heart failure, and 6 patients (25.0%) died; while there were no readmitted cases or fatal cases in compliance group (χ 2=33.49, 19.20; P<0.05). Conclusion:Early application of sacubitril and valsartan sodium in patients with acute HFrEF after hemodynamic stabilization can significantly improve left ventricular remodeling, for those with earlier escalation to the target dose, it is more beneficial. The changes of serum sST2 and inflammatory factor level after treatment may predict the efficacy of sacubitril/valsartan therapy.

Objective:To analyze the cause of varicocele (VC) recurrence and investigate the efficacy of sub-inguinal microsurgical varicocelectomy (MV) for recurrent VC.Methods:All of 16 inpatients diagnosed as recurrent VC, in the Department of Andrology of the Affiliated Hospital of Qingdao University from 2015 April to 2019 April, were performed sub-inguinal MV. The age of the inpatients was 18-36 years old, median 27 years old.5 cases were originally performed retroperitoneal high ligation of spermatic vein and other 11 cases were originally performed laparoscopic varicocelectomy. During the review one to three years after the previous operation, all of 16 patients were diagnosed as VC recurrence. The complains of these patients during the review included male subfertility (10 cases) and scrotal pain (12 cases), in which 6 cases’ complains were male subfertility with scrotal pain. After admission, 13 patients were classified as Grade Ⅲ (left in 8 cases, bilateral in 5 cases) and 3 patients as Grade Ⅱ (all left). The median of their visual analogue scale (VAS) was 2.5. Color doppler flow imaging (CDFI) grading showed: Grade Ⅲ in 12 cases (left in 7 cases, bilateral in 5 cases), Grade Ⅱ in 4 cases (all left). Particularly, 12 of them were Graded as Ⅲ simultaneously accompanying with Nut-cracker Phenomenon (NCP). Preoperative tests showed that the average serum testosterone was (16.2±4.9)nmol/ml, the average sperm concentration was (11.8±3.9)×10 6/ml and the progressive motility rate (PR) was (24.4±4.2)%. All of the patients were performed sub-inguinal MV using general anesthesia and supine position. The spermatic cords were clearly exposed and padded up by inserting gauze strips under them. During the operation, the field was magnified 4-6 times with the microscope. Then all of the dilated external and internal spermatic veins were ligated, at the same time the internal spermatic artery and lymph vessels were well preserved. During these operations, 11 patients underwent left-side MV, while other 5 did bilateral MVs. During these MVs, we found twisted and dilated external and internal spermatic veins in all cases and well preserved the internal spermatic arteries and lymph vessels. The number of ligated left and right external spermatic veins were(2.1±0.6) and (1.4±0.5)respectively and the number of ligated left and right internal spermatic veins were (10.1±1.1) and (6.6±0.5) respectively. We also found out(1.3±0.5) internal spermatic arteries and (3.0±1.0)lymph-vessels on left side. On right side, there were (1.4±0.5) internal spermatic arteries and (2.6±0.5) lymph-vessels respectively. At last, we summarily analyzed the pre-operative and post-operative VAS, serum testosterone, CDFI and semen analysis data. Results:All of the 16 sub-inguinal MVs were successfully performed. All patients were reviewed comprehensively 6 months after MV. The reviewed results showed that the post-operative VAS was significantly reduced ( Z=-2.994, P<0.05), palpable scrotal vessels disappeared and Valsalva tests were negative. No obvious reflux of internal spermatic veins were detected by CDFI. Interestingly, the sperm concentration and motility were both significantly improved 6 months after MV ( P<0.05), while there was not remarkable increase of the serum testosterone after MV ( P>0.05). During the follow up, no testicular atrophy, hydrocele and other complications were found. Up to submission, five of the ten patients who presented for male subfertility have impregnated their wives. Conclusions:The most possible cause of VC recurrence could be the omission of the external and internal spermatic veins, particularly in the grade Ⅲ VC patients or VC accompanied with NCP. The sub-inguinal MV, which can discover more twisted spermatic veins and at the same time preserve the spermatic artery and lymph-vessels, shows better clinical efficacy than other procedures.

OBJECTIVE: To explore the genetic basis for a pedigree affected with Alport syndrome. METHODS: Next generation sequencing and Sanger sequencing was carried out to detect potential variant of the COL4A5 gene among members from the pedigree and 100 unrelated healthy controls. RESULTS: A novel missense c.3293G>T (p.Gly1098Val) variant was found in the COL4A5 gene among 6 affected members but not the unaffected members of the pedigree or the 100 healthy controls. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.3293G>T variant was classified as pathogenic (PP1-strong+PM1+PM2+PP3+PP4). CONCLUSION By destructing the Gly-X-Y structure of its protein product, the c.3293G>T variant of the COL4A5 gene probably underlies the Alport syndrome in this pedigree. Above finding has enriched the spectrum of COL4A5 variants.

OBJECTIVE: To analyze variant of IDS gene in a pedigree affected with mucopolysaccharidosis type II (MPS II). METHODS: The proband was subjected to next generation sequencing and Sanger sequencing to identify potential variants. Suspected variant was analyzed by its co-segregation with the disease in the pedigree. Its impact on mRNA splicing was analyzed by using reverse transcription PCR (RT-PCR). RESULTS: A hemizygous IVS1-3T>G variant was found in the IDS gene in the proband. RT-PCR results revealed two abnormal cDNA fragments of 600 bp and 300 bp. The 600 bp fragment had inserted 216 nucleotides at the 3' end of intron 1, while the 300 bp fragment had lost 109 nucleotides at the 5' end of exon 2, which resulted in two truncated proteins comprising 38 and 92 amino acids, respectively, instead of the normal product (550 amino acids). The proband and his mother were respectively hemizygous and heterozygous for the variant. The same variant was not found among 100 normal controls. CONCLUSION The IVS1-3T>G variant of the IDS gene probably underlies the MPS II in this pedigree by causing reduction or elimination of the IDS protein.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
Asian Continental Ancestry Group ; B-Lymphocytes ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; Prednisone ; Prognosis ; Rituximab ; Vincristine

Objective To examine the expression profile of programmed death-ligand 1 (PD-L1) on lung endothelial or epithelial cells,and to determine the specific role of PD-L1 in mouse model of indirect acute lung injury (i-ALI).Methods Eighty male C57BL/6 mice were randomly divided into two parts (both n =40).The effects of different administration routes on the expression of PD-L1 were observed.The mice in each part were randomly divided into sham,i-ALI,i-ALI+small interfering RNA (siRNA) random sequence control,and i-ALI+PD-L1 siRNA which could specifically inhibit PD-L1 expression groups,with l0 mice in each group.i-ALI was reproduced in a mouse model of hemorrhagic shock in combination with a subsequent cecal ligation and puncture (CLP).In sham group,only bilateral femoral arteries were ligated without catheterization or bleeding,and only cecum was separated but perforation was not ligated.Intravenous or intratracheal delivery of PD-L1 siRNA was performed 2 hours following the resuscitation to suppress the expression of PD-L1 on lung endothelial or epithelial cells.The mice in i-ALI+siRNA random sequence control group were given siRNA random sequence without inhibition effect on PD-L1 expression,and those in sham group and i-ALI group were given 100 μL phosphate buffered saline (PBS).The mice were sacrificed at 24 hours after CLP,and samples of blood,lung tissue and bronchoalveolar lavage fluid (BALF) were harvested.Expressions of PD-L1 were determined with flow cytometry.Cytokines and chemokines in plasma,lung tissue and BALF were determined by enzyme linked immunosorbent assay (ELISA).The protein concentration in plasma and BALF and the activity of myeloperoxidase (MPO) in lung tissue were quantitatively measured.The pathological changes in lung tissue were observed under light microscope.Results ① Compared with sham group,PD-L1 expression on lung endothelial or epithelial cells were significantly elevated in i-ALI group [endothelial cells:(27.88 ± 1.53)％ vs.(19.64 ± 1.03)％,epithelial cells:(58.70 ± 8.21)％ vs.(29.23 ± 3.94)％,both P ＜ 0.05].② Mice received intravenous delivery of liposomal-encapsulated siRNA had significantly lower expression of PD-L1 on lung endothelial cells as compared with that of i-ALI group [(21.37 ± 0.76)％ vs.(27.88 ± 1.53)％,P ＜ 0.05].Intratracheal delivery of naked PD-L1 siRNA mainly inhibited the PD-L1 expression on epithelial cell as compared with that of i-ALI group [(31.23±4.71) ％ vs.(58.70±8.21) ％,P ＜ 0.05].The expression of PD-L1 in pulmonary microvascular endothelial cells or pulmonary epithelial cells of i-ALI mice was not affected by siRNA random sequence.③ PD-L1 silencing on pulmonary endothelial cells induced by intravenous delivery of PD-L1 siRNA led to a lower protein ratio of BALF/plasma [(4.48 ± 0.35) × 10-3 vs.(6.11 ± 0.56) × 10-3,P ＜ 0.05] and a decreased MPO activity in lung tissue (U · μg-1 · min-1:2.48 ± 0.47 vs.4.56 ± 0.52,P ＜ 0.05) as compared with that of i-ALI group.Moreover,inflammatory mediator levels such as interleukin-6 (IL-6),monocyte chemoattractant protein-1 (MCP-1),macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) in lung tissue or plasma were significantly reduced following PD-L1 suppression on endothelial cells as compared with those of i-ALI group [IL-6 (ng/g):177.4±23.2 vs.287.9±57.3,MCP-1 (ng/g):839.6±91.7 vs.1 395.7±211.9,MIP-2 (ng/g):923.7± 107.3 vs.1 700.9±240.2 in lung tissue;IL-6 (ng/L):950.2±192.7 vs.1 828.2±243.6,TNF-α (ng/L):258.7±29.1 vs.443.0 ± 58.1,MCP-1 (ng/L):2 583.8±302.3 vs.4 328.1 ±416.4,MIP-2 (ng/L):1 512.9± 165.6 vs.2 005.9 ± 85.7 in plasma,all P ＜ 0.05],however,there was no significant change in the levels of inflammatory factors in BALF.It was shown in lung tissue histology that PD-L1 silencing on pulmonary endothelial cells induced by intravenous delivery of PD-L1 siRNA led to lessened pulmonary edema and reduced immune cells emigration.Intratracheal delivery of PD-L1 siRNA for PD-L1 suppression on epithelial cells had minimal effects on protein ratio of BALF/plasma,MPO activity,inflammatory mediator expressions in lung tissue,plasma,and BALF as well as lung tissue histology.Conclusion PD-L1 silencing on endothelial cells but not epithelial cells protected mice against hemorrhagic shock-sepsis induced i-ALI.

Surface electromyography (sEMG) has been widely used in the study of clinical medicine, rehabilitation medicine, sports, etc., and its endpoints should be detected accurately before analyzing. However, endpoint detection is vulnerable to electrocardiogram (ECG) interference when the sEMG recorders are placed near the heart. In this paper, an endpoint-detection algorithm which is insensitive to ECG interference is proposed. In the algorithm, endpoints of sEMG are detected based on the short-time energy and short-time zero-crossing rates of sEMG. The thresholds of short-time energy and short-time zero-crossing rate are set according to the statistical difference of short-time zero-crossing rate between sEMG and ECG, and the statistical difference of short-time energy between sEMG and the background noise. Experiment results on the sEMG of rectus abdominis muscle demonstrate that the algorithm detects the endpoints of the sEMG with a high accuracy rate of 95.6%.