[Analysis of the safety, accuracy, and factors influencing bleeding complications in CT-guided puncture biopsy of brain occupying lesions].

Objective: To investigate the safety and accuracy of CT-guided intracranial puncture biopsy and the possible influencing factors of postoperative bleeding complications. Methods: A case series study. A retrospective analysis was conducted on 101 patients who underwent CT-guided intracranial puncture biopsy at the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021. The basic data of patients and the safety and accuracy of CT-guided intracranial puncture biopsy were analyzed statistically. Univariate and multivariate logistic regression analysis were used to screen the influencing factors of bleeding complications in CT-guided intracranial puncture biopsy, and the bleeding complications in glioma subgroup were analyzed. Results: Among the 101 patients, 53 were males and 48 were females, aged (53.7±17.2) years. The average diameter of intracranial lesions was (3.5±1.4) cm, while the vertical distance from the lesion to the meninges was (2.4±1.7) cm. The needle's intracranial depth reached (3.2±1.8) cm, with adjustments averaging (3±1) occurrences and an average procedural duration of (40.2±12.9) minutes. Pathological diagnoses included glioma (36 cases), gliosis (3 cases), lymphoma (32 cases), metastatic tumors (7 cases), inflammatory lesions (13 cases), and 10 indeterminate cases. The positive rate of puncture pathology was 90.1% (91/101), and the diagnostic coincidence rate was 94.0% (78/83). The incidence of bleeding complications in CT-guided intracranial puncture biopsy was 26.7% (27/101), of which 23 cases had small intratoma or needle path bleeding, 4 cases had massive bleeding, and 2 cases died. The patients were divided into bleeding group (n=27) and no bleeding group (n=74), according to the presence or absence of bleeding. The results of univariate logistic regression analysis showed that thrombin time≥15 s and the number of needle adjustment were the factors affecting the occurrence of bleeding complications (both P<0.05), and the results of multivariate logistic regression showed that thrombin time≥15 s was the related factor for bleeding. Patients with thrombin time≥15 s had a 3.045 times higher risk of bleeding than those with thrombin time<15 s (OR=3.045,95%CI:1.189-7.799,P=0.020). Among the 101 patients, 36 cases of midbrain glioma were divided into low-grade glioma group (n=11) and high-grade glioma group (n=25) according to the pathological grade. Subgroup analysis showed that the risk of bleeding for high-grade gliomas was 9.231 times higher than that for low-grade gliomas (OR=9.231,95%CI:1.023-83.331,P=0.031). Conclusions: CT-guided intracranial puncture biopsy is safe and feasible with high accuracy. Complication rates are associated with thrombin time≥15 s, especially high-grade glioma, which increases the risk of postoperative bleeding.

[Clinical and genetic spectrum of 6 cases with asparagine synthetase deficiency].

Objective: To explore the clinical and genetic characteristics of asparagine synthase deficiency. Methods: Case series studies. Retrospective analysis and summary of the clinical data of 6 cases with asparagine synthase deficiency who were diagnosed by genetic testing and admitted to the Third Affiliated Hospital of Zhengzhou University from May 2017 to April 2023 were analyzed retrospectively. The main clinical features, laboratory and imaging examination characteristics of the 6 cases were summarized, and the gene variation sites of them were analyzed. Results: All of the 6 cases were male, with onset ages ranging from 1 month to 1 year and 4 months. All of the 6 cases had cognitive and motor developmental delay, with 3 cases starting with developmental delay, 3 cases starting with convulsions and later experiencing developmental arrest or even regression. All of 6 cases had epilepsy, in whom 2 cases with severe microcephaly developed epileptic encephalopathy in the early stages of infancy with spasms as the main form of convulsions, 4 cases with mild or no microcephaly gradually evolved into convulsions with no fever after multiple febrile convulsions with focal seizures, tonic clonic seizures and tonic seizure as the main forms of convulsions. Three cases of 4 gradually developed into stagnation or even regression of development and ataxia after multiple convulsions with no fever. There were normal cranial imaging in 2 cases, dysplasia of the brains in 1 cases, frontal lobe apex accompanied by abnormal white matter signal in the frontal lobe and thin corpus callosum in 1 case, thin corpus callosum and abnormal lateral ventricular morphology in 1 case, and normal in early stage, but gradually developing into cerebellar atrophy at the age of 5 years and 9 months in 1 case. Two cases underwent visual evoked potential tests, the results of which were both abnormal. Three cases underwent auditory evoked potential examination, with 1 being normal and 2 being abnormal. All of 6 cases had variations in the asparagine synthase gene, with 2 deletion variations and 7 missense variations. The variations of 2 cases had not been reported so far, including c.1341_1343del and c.1283A>G, c.1165_1167del and c.1075G>A. The follow-up time ranged from 3 months to 53 months. Two cases who had severe microcephaly died in infancy, while the other 4 cases with mild or no microcephaly were in survival states until the follow-up days but the control of epilepsy was poor. Conclusions: Asparagine synthase deficiency has a certain degree of heterogeneity in clinical phenotype. Children with obvious microcephaly often present as severe cases, while children with mild or no microcephaly have relatively mild clinical manifestations. The variation of asparagine synthetase gene is mainly missense variation.

[Efficacy analysis of hepatic arterial infusion chemotherapy combined with targeted and immune therapy followed by 125I seeds implantation in the treatment of hepatocellular carcinoma with portal vain tumor thrombus].

Objective: To investigate the safety and efficacy of Hepatic Arterial Infusion Chemotherapy(HAIC) combined with targeted and immune therapy followed by 125I seeds implantation in portal vain tumor thrombus (PVTT) in the treatment of hepatocellular carcinoma(HCC) with PVTT. Methods: A retrospective study was performed on the clinical data of 21 patients [ (11 men, 10 women) aged 34-73 (52.6±13.7) years] with HCC with PVTT in The First Affiliated Hospital of Zhengzhou University from October 2020 to October 2022, all of them were treated with HAIC plus targeted and immune therapy,and 125I seeds implanted into PVTT. The patients were followed up to January 2023, the efficacy was evaluated according to the modified version of the solid tumor efficacy evaluation criteria (mRECIST). The progression-free survival (PFS) rate, overall survival(OS) rate and portal tumor thrombus control rate at 3, 6, 12 and 18 months after treatment were recorded, and PFS and OS time were followed up. The changes of liver function, AFP, coagulation function and adverse events were observed. Results: Each patient received 2 to 7 (mean: 3.3±1.2) cycles of HAIC. 10-37 seeds (mean:16.6±6.7) were implanted per patients. The median follow-up time was 15 (range from 5 to 25) months.During the follow-up time, 15 patients showed progression and 6 patients died, and the PFS rates at 3, 6, 12, and 18 months after treatment were 90.5%, 71.4%, 42.9%, and 23.8%, respectively, and at 3, 6, 12, and 18-month OS rates were 100%, 100%, 81.0%, and 61.9%, respectively.The PVTT control rates at 3, 6, and 12 months were 90.5%, 90.5%, and 62.5%, respectively. Overall efficacy evaluation of CR rate 0, PR rate 47.6% (10/21), SD rate 38.1% (8/21), and PD rate 14.3% (3/21). The total incidence of treatment-related adverse events was 100%.Grade 3 treatment related adverse events were observed for 4 cases, the rest wereⅠtoⅡadverse events. Right upper abdominal pain, fever and hemorrhage in liver capsule related to the procedures were observed in 11(52.4%), 5(23.8%) and 3(14.3) patients, respectively. Conclusion: HAIC combined with targeted and immune therapy followed by 125I seeds implantation in PVTT is a safe and efficacy therapy for HCC with PVTT.

The effect of previous orbital decompression on outcomes of rectus muscle recession surgery in patients with thyroid ophthalmopathy.

PURPOSE: To evaluate the effect of previous orbital decompression on outcomes of rectus muscle recession surgery in patients with thyroid-associated ophthalmopathy. METHODS: This retrospective study enrolled 55 eyes of 33 patients treated in our hospital for restrictive strabismus caused by thyroid-associated ophthalmopathy. We performed muscle recession for the obviously restricted extraocular muscles, with 6 weeks of follow-up. Surgical outcomes were compared between the orbital decompression group (DG, n=15) and non-orbital decompression group (NDG, n=18). RESULTS: A total of 33 patients with Graves' ophthalmopathy who underwent rectus muscle recession surgery were included. Of these, 15 patients had undergone orbital decompression prior to strabismus surgery, and 18 had not. The two groups did not differ in terms of the preoperative horizontal or vertical ocular deviation, degree of restriction of eye movement, degree of diplopia, or mean number of muscles that underwent surgery (P>0.05). There was no significant difference in the preoperative horizontal or vertical ocular deviation, level of eye movement restriction, degree of diplopia and the success rate of the surgery (P>0.05). CONCLUSION: Rectus muscle recession surgery in patients with thyroid-associated ophthalmopathy during the quiescent period could improve the ocular deviation and diplopia, and orbital decompression performed before strabismus surgery had no significant effect on surgical technique or outcomes of rectus muscle recession surgery.

[Analysis of the safety and diagnostic efficiency of CT-guided percutaneous biopsy of pancreatic space-occupying lesions using large needle:comparison of trans-organ biopsy approach and non-trans-organ biopsy approach].

Objective: To compare the safety and diagnostic efficiency of CT-guided trans-organ and non-trans-organ large needle biopsy in the diagnosis of pancreatic space-occupying lesions. Methods: The clinical data of 367 patients with pancreatic mass who underwent CT-guided percutaneous biopsy in the First Affiliated Hospital of Zhengzhou University from January 2019 to January 2022 were retrospectively analyzed, including 211 males and 156 females, aged 18 to 87 (60.7±11.8) years old. They were divided into a trans-organ route group (n=142) and a non-trans-organ route group (n=225) according to whether traversing the organs during the procedures. The imaging data, pathological results, puncture process and complications of patients of the two groups were recorded. The successful rate for obtaining tissue,one-time successful diagnosis rate, accuracy, sensitivity, specificity, false negative rate and the incidence of complications were compared between the two groups. Results: There was no significant difference in baseline data between the two groups (all P>0.05).There were 28, 57, 24, and 33 biopsies were performed via a pathway traversing liver, stomach, small bowel and colon, respectively. The overall sampling success rates of the two groups were 100%.The one-time successful diagnosis rate did not show statistically difference between the two groups [86.6%(123/142) vs 87.1%(196/225),P=0.892]. There was no statistically difference in accuracy, sensitivity and false negative rates between trans-organ route group and non-trans-organ routegroup [92.3%(131/142) vs 92.0%(207/225), 91.8% (123/134) vs 90.0%(190/211) and 8.2% (11/134) vs 10.0%(21/211), all P>0.05]. The specificity was 100% in both groups. The common complications of the two groups were increased pancreatic amylase and hematoma, and there was no significant difference in the incidence of complications between the trans-organ route group and the non-trans-organ route group [10.6% (15/142) vs 12.4% (28/225), P=0.585]. In the trans-organ route group, 5 patients had increased pancreatic amylase and 10 patients had local hematoma, all of which were improved after conservative treatment. In the non-organ route group, 11 patients had elevated pancreatic amylase, and 17 patients had local hematoma, 1 case received surgical treatment due to bleeding, the rest were improved by conservative treatment. Conclusion: CT-guided percutaneous transabdominal organ large needle biopsy of pancreatic space-occupying lesions has the comparable diagnostic efficiency and safety as non-transabdominal organ approach.

[Safety and efficacy of cryoablation versus radiofrequency ablation for stage â non-small-cell lung cancer].

Objective: To compare the safety and efficacy of cryoablation(CYA) and radiofrequency ablation(RFA) for stageⅠnon-small cell lung cancer(NSCLC). Methods: From January 2014 to January 2019, 90 eligible patients [48 males, 42 females, age: 39-85(63.6±10.1)years] in the First Affiliated Hospital of Zhengzhou University met the inclusion criteria were retrospectively analyzed. They were divided into 2 groups according to different treatment methods(group CYA and group RFA). The duration of operation, intraoperative pain, local tumor progression rate and the incidence of complications were compared. The progression-free survival (PFS) and overall survival (OS) of the 2 groups were estimated by Kaplan-Meier curves, and were compared by using log-rank test. Results: The clinical data and tumor situation of the patients between two groups did not show significant differences. The mean duration of operation for group CYA was longer than that for group RFA [(73.5±17.2)min vs (51.4±18.7)min, P<0.001];the mean intraoperative visual analogue score(VAS)for group CYA was lower than that for group RFA (0.53±0.89 vs 3.44±2.44, P<0.001). The median follow-up period time were 53 months and 52 months for group CYA and RFA. At the end of the study, The local tumor progression rate was 31.6%(12/38) and 25.0%(13/52) for group CYA and group RFA, the difference were not statistically(P=0.491). There was no statistical difference for progress-free survival(PFS)between group CYA and group RFA[51(95%CI:40.3-55.0)months)vs 44(95%CI:37.2-54.1) months, P=0.649]. The median OS was not reached in both groups. The most common complications observed in the two groups were pneumothorax, hemorrhage and pleural effusion. There was no statistical difference in the incidence rates [42.1%(16/38) for group CYA vs 28.8% (15/52)for group RFA, P=0.191]. The incidence rate of pleural effusion for group CYA was higher than that for group RFA [26.3%(10/38)vs 5.8%(3/52), P=0.006]. The incidence rates of pneumothorax and hemorrhage had no statistical difference between the two groups [13.3%(5/38)vs 13.5% (7/52) and 15.8%(6/38) vs 9.6% (5/52), all P>0.05]. Conclusion: Compared with RFA,CYA shows no significant differences in the same efficacy and safety for treating patients with stage Ⅰ NSCLC, with less intraoperative pain but longer operative duration.

[Mid-term efficacy of sacral nerve stimulation for the treatment of chronic constipation].

Objective: To investigate the mid-term efficacy of sacral nerve stimulation (SNS) for chronic constipation. Methods: A descriptive case series study was conducted. Patients with chronic constipation were treated in Xijing Hospital of Digestive Disease from February 2013 to December 2018 were retrospectively enrolled. The types of constipation were confirmed based on colon slow transit test, anorectal manometry and defecography in Xi'an Mayinglong Coloproctological Hospital. This study has been registered in China clinical trial registry (Registration No.: ChiCTR-ROC-16008945). Case inclusion criteria: (1) constipation was diagnosed according to Rome III criteria; (2) traditional treatment, including education, diet adjustment, laxative, biofeedback treatment, failed for at least 1 year; (3) there were no constipation-related organic diseases. After excluding neurogenic diseases, including spinal cord injury and multiple sclerosis, 21 patients were included in this study. There were 10 males and 11 females, with an average age of 50.9 (14-76) years. After the relevant examination and evaluation of patients, they underwent percutaneous nerve evaluation (PNE). If patient experienced a good response to PNE after 2 or 3 weeks (≥50%), permanent SNS implantation was performed. The improvement of clinical symptoms and quality of life between the baseline, PNE, and latest follow-up time points were compared. Improvement of clinical symptoms, including autonomic stool frequency per week, autonomic stool days per week, defecation time, visual analogue scale (VAS, lower score indicates more serious symptoms) score and Cleveland clinic constipation score (CCCS, higher score indacates more serious symptoms) criteria. The change of quality of life was scored by SF-36 questionnaires (the higher score indicates better quality of life). Results: Of 21 patients, 18 (85.7%) experienced significant improvement in symptoms with PNE, and 2 patients discontinued treatment due to their dissatisfaction. Sixteen patients (76.2%) received permanent SNS implantation, two of whom underwent bilateral PNE implantation. These patients were followed-up for mean 56 (34-72) months. The treatment was continuously effective in 13 patients (61.9%), including 3 of ODS, 1 of STC and 9 of mixed constipation. Compared with baseline, the score of constipation patients receiving permanent SNS implantation at latest follow-up was shown. The median autonomic stool frequency per week increased from 1.0 (0-7) to 7.5 (0-10) (P<0.001), the median autonomic stool days per week increased from 1.0 (0-7) d to 4.5 (0-7) d (P<0.001), the median defecation time decreased from 19.0 (8-40) minutes to 4.0 (3-31) minutes (P<0.001), the median CCCS decreased from 20.0 (13-30) to 9.0 (6-30) (P<0.001), and the median VAS score increased from 9.0 (7-40) to 80.0 (15-90) (P<0.001). The values of the 8 parts of the SF-36 questionnaire increased (all P<0.05). Conclusion: SNS implantation is safe and has obvious effects on severe constipation with stable mid-term efficacy.

Sentinel lymph node biopsy with carbon nanoparticle suspension after neoadjuvant chemotherapy for breast cancer patients.

INTRODUCTION: The aim of the study was to explore the feasibility of performing sentinel lymph node biopsy (SLNB) using a carbon nanoparticle suspension (CNPS) after neoadjuvant chemotherapy in breast cancer patients. METHODS: Some 152 patients diagnosed with primary breast cancer (cT1-3N0-2M0) were recruited. Patients were divided into two groups according to axillary lymph node (ALN) status after four to six cycles of neoadjuvant chemotherapy. All patients received a CNPS injection, after which SLNB and axillary lymph node dissection (ALND) were performed. RESULTS: Sentinel lymph nodes (SLN) of 143 patients were identified; with an accuracy rate of 94.4% and a false-negative rate of 9.9%. Group A included 67 patients, and the detection, accuracy and false-negative rates within this group were 95.5%, 96.9% and 6.7%, respectively. The corresponding rates for group B (85 patients) were 92.9%, 92.4% and 11.8%, respectively. CONCLUSIONS: CNPS is an ideal tracer for improving the detection rate of SLN and can be used to determine SLN status following neoadjuvant chemotherapy.

microRNA-29b mediates Th17/Treg imbalance in chronic obstructive pulmonary disease by targeting IL-22.

Chronic obstructive pulmonary disease (COPD) represents a chronic inflammatory disorder of the airways induced mainly by cigarette smoking. In the current study, cigarette smoke extract (CSE) was used to develop an in vitro COPD model using human bronchial epithelium (HBE) cells to expound the possible role of microRNA-29b (miR-29b) in COPD. Firstly, miR-29b and interleukin (IL)-22 expression was assessed in serum of 20 healthy non-smokers, 20 healthy smokers and 20 COPD patients as well as CSE-treated HBE cells. Then, miR-29b and IL-22 expression was altered to evaluate their functions in Th17/Treg ratio. miR-29b inhibited Th17/Treg ratio and levels of IL-22; whereas overexpression of IL-22 reversed these trends. Moreover, rescue experiments found that IL-22 neutralized the repressive effects of miR-29b on Th17/Treg ratio and inflammatory response. Finally, we found that miR-29b blocked the JAK/STAT3 pathway in CSE-treated HBE cells. These data highlighted that miR-29bs modulated Th17/Treg imbalance in CSE-induced experimental COPD through inhibition of IL-22-dependent JAK/STAT3 pathway.

[Functional evaluation after function-preserving gastrectomy].

With the increase of people's health awareness and the progress of medical diagostic technology in recent years, the diagnosis rate of early gastric cancer is increasing year by year. Although radical surgery has good efficacy, how to maximize the preservation of the normal anatomy and function of the stomach and improve the quality of life of patients in the pursuit of radical surgery has become a more important issue in the treatment of early gastric cancer. Under the condition of ensuring radical lymph node dissection, function-preserving gastrectomy can fully preserve gastric function by reducing the resection extent and preserving the pylorus and the vagus nerve, which has advantage of improving quality of life and has great potential in the treatment of early gastric cancer. However, there is no functional evaluation standard for function-preserving gastrectomy at present. Most of the patients are evaluated by quality of life scale, which is relatively subjective. Even though the evaluation of endoscopy, hematology and other objective means can indicate the benefit degree in quality of life brought by functional reconstruction, the evidence level is limited. Therefore, this paper discusses the research status of function-preserving gastrectomy evaluation, postoperative complications, postoperative nutritional status, auxiliary examination and other items in the evaluation of gastric function, and analyzes the prospects of research direction in this field.

[Clinical effects of surgical treatment of high myopic strabismus fixus by modified Yokoyama's surgery combined with medial rectus muscle recession].

Objective: To analyze clinical effects of modified Yokoyama's surgery combined with medial rectus muscle recession for treatment of high myopic strabismus fixus. Methods: Retrospective analysis of records of 9 patients (14 eyes) with high myopic strabismus fixus treated from February 2013 to December 2016 in the Department of Ophthalmology, Xiangya Hospital, Central South University. All patients underwent modified Yokoyama's surgery. The temporal 1/2 of the superior rectus (SR) and the superior 1/2 of the lateral rectus (LR) were united 12 to 14 mm, combined with medial rectus muscle recession. The angle of deviation of primary position, the mobility of the affected eye, and the change of CT imaging were observed and analyzed before and 6 months after surgery. Statistical analysis was performed by Mann-Whitney U test. Results: The patients were 5 females and 4 males with an average age of (60±10) years. The duration of high myopia was (33.33±6.61) years. The refractive power was (-23.32±5.95) D, and the axial length was (33.04±2.63) mm. The recession mount of medial rectus was (7.2±2.1) mm (4.0-10.0 mm) intraoperatively. At 6 months, the median esotropia improved from 130 (80-140) prism diopter (PD) to 0 (0-10) PD, and the hypotropia from 20 (15-25) PD to 0 (0-5) PD. The median abduction limitation decreased from -3 (-4--1) to -1 (-2-0), and the median limitation of elevation decreased from -2 (-4--1) to 0 (-1-0). The angle of esotropia and hypotropia significantly improved (Z=-2.67, -2.70; P=0.008, 0.007), and the restriction of abduction and elevation decreased (Z=-3.35, -3.24; both P=0.001). Only 3 patients' CT images were enrolled in a comparative study. Preoperative orbital CT scans showed inferior LR displacement and medial SR displacement with the posterior portion of the eyeball to the superotemporal quadrant of the orbit. After surgery, the mean reduction ratio of dislocation degree of the 3 patients was 28.97%, the dislocation of LR and SR was reduced, and the posterior global part was correctly positioned within the orbit. Conclusions: The modified Yokoyama's surgery combined with medial rectus muscle recession can effectively correct high myopic strabismus fixus, recover the eyeball anatomical position, and evidently improve eye mobility. The clinical effects are satisfactory. (Chin J Ophthalmol, 2019, 55: 670-676).

[Clinical Investigation on CT guided cryoablation for treating invasive chest wall or pleural tumors].

Objective: To evaluate the feasibility and short-term effect of CT guided cryoablation for malignant chest wall or pleural involvement. Methods: To follow up 22 patients with chest wall or pleural involvement of various malignancies who underwent cryoablation from January 2012 to January 2015 by conducting postoperative 1-, 3- and 6-month enhanced CT, MRI or PET-CT examinations, respectively, evaluate local curative effect, and observe their progression-free survival (PFS), postoperative pain remission and complications after the cryoablation. Results: A total of 22 patients with 27 lesions received 26 times of argon-helium cryoablation. According to the coverage situation of immediate postoperative ice balls on the lesions, they were divided into a complete coverage group (Group A with 18 patients) and a partial coverage group (Group B with 4 patients). 1 month later, 15 patients' tumors were completely ablated, and 3 had residue and thus received the second cryoablation in Group A, while all patients' tumors had residue in Group B. 3 months later, 17 patients' tumors were completely ablated, and 1 had residue and thus received another cryoablation in Group A, while all patients' residual tumors enlarged in different extent in group B. 6 months later, all lesions were ablated in group A while all patients' residual tumors enlarged in group B. For the 22 patients, their preoperative, and postoperative 1-week, 1-month, 3-month, and 6-month VAS scores were 4.95±0.57, 1.45±0.35, 1.45±0.35, 1.64±1.71, and 2.00±2.35, respectively. The differences in the preoperative, postoperative 1-week, and postoperative 1-month scores are significant statistically (P<0.05), and the difference in the postoperative 1-month and 6-month scores is also with statistical significance (P=0.03). For all patients, their post-operative 1-week, 1-month, 3-monte and 6-month pain remission rates are 90.9%(20/22), 90.9%(20/22), 86.4% (19/22)and 81.8%(18/22), respectively. With a median follow-up of 13.5 months, the median PFS is 7 months. The adverse effect after argon-helium cryoablation involved transitory worsened pain (16 cases), pleural effusion (5 cases, including 3 underwent closed drainage), fever (5 cases), and hemoptysis (3 cases). Conclusion: CT guided argon-helium cryoablation is a safe and effective method to treat malignant chest wall or pleural involvement.

Simultaneous detection of 45 fusion genes in leukemia by dual-color fluorescence real-time PCR.

INTRODUCTION: Detection of recurrent genetic abnormalities is of great significance for a refined diagnosis and assessment of prognosis in leukemia. Conventional nested reverse transcription PCR is labor intensive and time-consuming. METHODS: We have developed a novel dual-color TaqMan probe-based real-time PCR method for the simultaneous screening of 45 fusion transcripts in 12 parallel reactions. The method was tested and validated with cell lines carrying known fusion transcripts and patient samples. RESULTS: A multiplex real-time PCR method was successfully developed for rapid detection of 45 fusion genes and validated for 15 of the more commonly detected fusion genes. Intra-assay reproducibility assessed for the most frequent rearrangements ranged from 0.41% to 0.74% for the coefficient of variation (CV) of cycle threshold (Ct) and the interassay reproducibility ranged from 1.62% to 2.83% in five separate experiments. The lowest detection limit for the translocations tested ranged between 1 : 16 000 and 1 : 32 000. Validation of the method with 213 patient samples showed 100% specificity and excellent consistence with conventional nested RT-PCR. CONCLUSION: Overall, we believe that this method is easily applicable, cost-effective, and clinically useful for a rapid screening of fusion genes in the initial diagnostic phase of leukemia. Its use can also be extended to the monitoring of minimal residual disease.

Combination of IL-6, IL-10, and MCP-1 with traditional serum tumor markers in lung cancer diagnosis and prognosis.

Early detection and treatment is critically important for lung cancer patients. Inflammatory mediators such as IL-6, IL-10, and MCP-1 participate in lung cancer regulation. CEA, CA125, and ProGRP are commonly used serum tumor markers for lung cancer. In this study, we assessed the sensitivity and specificity of CEA, CA125, and ProGRP when used in combination with IL-6, IL-10, and MCP in lung cancer diagnosis. Serum from three different groups (healthy controls, individuals with high risk for lung cancer, and lung cancer patients) was collected. Electrochemiluminescence was used to detect expressions of CEA, CA125, and ProGRP; ELISA was used to examine serum levels of IL-6, IL-10, and MCP-1. Specificity and sensitivity of single as well as combination markers in lung cancer diagnosis were determined. Results indicated that CEA, CA125, ProGRP, and MCP-1 were significantly up-regulated in lung cancer patients as compared to those in controls and high risk individuals. Higher IL-6 and IL-10 levels were observed in both lung cancer patients and high-risk individuals as compared to those in controls. Highest sensitivity (95.2%) in cancer diagnosis was achieved when all six markers were used. This was followed by a combination of IL-6, IL-10, CEA, CA125, and ProGRP (92.6%). The most sensitive (88.6%). Four-marker combination was composed of IL-6, CEA, CA125, and ProGRP. As the combined usage of CEA, CA125, ProGRP, IL-6, IL-10, and MCP-1 significantly improved sensitivity of lung cancer detection; this biomarker arrangement may be beneficial for early diagnosis, treatment, and prognosis of lung cancer.

[The regulative effcets of A2a adenosine receptor on expression of SOCS-3 in rats of hypoxic pulmonary hypertension].

OBJECTIVE: To study the regulative effects and mechanism of A2aAR on expression of suppressor of cytokinesignaling-3(SOCS-3) in hypoxic pulmonary hypertension rats. METHODS: Sprague-Daeley rats were randomly divided into 3 groups: a normal control group, a hypoxia group, and a hypoxia with selective agonists of A2aAR group. Animals in the hypoxia groups were housed in a chamber with 8%- 11% O2 and 1%-3% CO2 for 8 hours (8: 00 AM to 4: 00 PM) daily for 28 days. They were treated intraperitoneally with either 4 ml/kg weight of normal saline or 0.2 mg/kg weight of CGS-21680 30 minutes before exposure to hypoxia. Four weeks later, mean pulmonary artery pressure (mPAP), mean carotid arterial pressure (mCAP) and right ventricular rate [RV/(LV+ S)] were measured. The expression of A2aAR and SOCS-3 in pulmonary arterioles was measured by immunohistochemistry. The expression of A2aAR mRNA and SOCS-3 mRNA in lung tissues were measured by real time RT-PCR. The expression of A2aAR protein and SOCS-3 protein in lung tissues were measured by Western blot. RESULTS: The mPAP in the hypoxia group was [(20.9±3.9)mmHg, 1 mmHg=0.133 kPa], significantly higher than the normal control group [(12.6±6.6)mmHg](P<0.01). The mPAP in CGS-21680 group was [ (14.8±3.8)mmHg], significantly lower than the hypoxia group(P<0.01). RV/(LV+ S) in the hypoxia group was [(35.2±2.0)%] , significantly higher than the normal control group [(29.6±2.7)%] (P<0.01). RV/(LV+ S) in the CGS-21680 group was [(28.3±8.8)%], significantly lower than the hypoxia group(P<0.01). WA/TA in the hypoxia group was (73±5, P<0.01), significantly higher than the normal control group. WA/TA in CGS21680 group was (54±3, P<0.01), significantly lower than the hypoxia group. A2aAR and SOCS-3 expressions on pulmonary arterioles in the hypoxia group were (0.134±0.034) and (0.119±0.011), both significantly higher than the normal group(P<0.01); and CGS-21680 treatment further increased their expressions. The mRNA expression of both molecules showed a 1.5-fold increase after 28-day hypoxia exposure. A2aAR activation by CGS-21680 treatment in hypoxia-exposed rats further increased the expression levels of A2aAR and SOCS-3 to about 2-fold higher than the normal controls. Furthermore, protein levels of A2aAR and SOCS-3 in the lung tissue were determined using Western blot. A similar increase was observed in hypoxia-induced pulmonary hypertension, and CGS-21680 treatment group showed the highest levels of these 2 proteins. CONCLUSION: A2aAR activation prevents hypoxia-induced pulmonary hypertension, and its mechanisms are related to the activation of A2aAR SOCS-3 signaling pathway.

[T-cell prolymphocytic leukemia: potential diagnostic pitfalls]. / Leucémie prolymphocytaire T : un piège diagnostique à connaître.

BACKGROUND: Sezary syndrome (SS) presents clinically as erythroderma, which may be pigmented, and pruritic, associated with peripheral lymphadenopathies. Erythroderma may also occur in a broad range of reactive and malignant conditions including T-cell prolymphocytic leukemia (T-PLL). We report a case initially diagnosed as SS but ultimately diagnosed as T-PLL based upon skin involvement. CASE REPORT: A 70-year-old man was referred by his hematologist for management of SS. Physical examination revealed lymphadenopathies and mild diffuse erythema without infiltration. His WBC count was elevated at 8.3 G/L. A peripheral blood smear showed Sezary-like cells. Flow cytometry of peripheral blood revealed prolymphocytic T-cells staining positively for CD2, CD3, CD4 and CD7. Cytogenetic studies showed chromosomal abnormalities in terms of number and structure with missing chromosomes 6 and13, as well as deletion of chromosome 17. Finally, a diagnosis of T-PLL was made. Pentostatin was initiated pending treatment with alemtuzumab, but the patient's overall condition deteriorated rapidly and he died 10 days later. DISCUSSION: Diagnosis of LPLT is based upon a number of factors. In the case presented herein, the clinically atypical nature of the skin lesions prompted the dermatologist to review the diagnosis. The morphology of the circulating T-lymphocytes and their immunologic and phenotypic characteristics finally ruled out the diagnosis of Sezary syndrome, while their association with compatible cytogenetic anomalies enabled a diagnosis of prolymphocytic leukemia to be made instead. CONCLUSION: Prolymphocytic leukemia involves complex differential diagnosis with regard to Sezary syndrome, posing potential pitfalls for hematologists and dermatologists.

Identification of a novel HLA-B*40 allele, HLA-B*40:211, in a Chinese individual.

HLA-B*40:211 allele differs from HLA-B*40:02:01 by an amino acid exchange at position 132, which has a missense mutation in exon 3 from Ser to Tyr.