[The preliminary efficacy of "quadri-combination" therapy on the treatment of bladder cancer].

To investigate the safety and efficacy of "quadri-combination" therapy including maximal transurethral resection of bladder tumor (mTURBT), combined with systemic chemotherapy and immunotherapy, concurrent radiotherapy, and immune maintenance therapy. The clinical data of 8 patients with bladder cancer who could not tolerate or refused radical cystectomy at the Department of Urology, Peking University Cancer Hospital from November 2019 to October 2021 were retrospectively analyzed. There were 5 males and 3 females with a mean age of 69 years. The Eastern Cooperative Oncology Group(ECOG) score was 0 in 6 cases and 1 in 2 cases. There were 5 cases of high-grade urothelial carcinoma (1 case of T3b; 2 cases were T2; 2 cases of T1 stage, with multiple tumors and repeated recurrence), 1 case of high-grade urothelial carcinoma with carcinoma in situ (T1/Tis stage), 1 case of high-grade urothelial carcinoma with squamous differentiation (T3b stage), and 1 case of high-grade urothelial carcinoma with glandular differentiation (T2). All patients underwent "quadri-combination" therapy.The patient's tolerance, success rate of bladder preservation and prognosis were evaluated.The median follow-up time was 22.5 (12-35) months. One patient with high-grade muscle-invasive bladder cancer (T2) received mTURBT, albumin-bound paclitaxel and durvalumab combined therapy for 3 cycles, concurrent radiotherapy, and immune maintenance therapy for 18 months, and the tumor recurrence was found. The pathology was high-grade urothelial carcinoma. Salvage radical cystectomy combined with pelvic lymph node dissection is recommended. The remaining 7 patients were regularly reexamined, and no recurrence or metastasis was found.The 2-year progression-free survival rate was 80%, and the success rate of bladder preservation was 87.5%(7/8). Treatment-related adverse reactions were resolved by symptomatic treatment, and patients' compliance and tolerance were acceptable.The "quadri-combination" bladder-preserving therapy is feasible and well tolerated, but further studies are needed.

[Safety and efficacy of laparoscopic microwave ablation combined with partial nephrectomy for renal tumors: initial experience].

Objective: To explore the safety and efficacy of laparoscopic microwave ablation combined with partial nephrectomy in the treatment of renal tumors. Methods: The 65 patients with renal tumors undergoing laparoscopic microwave ablation combined with partial nephrectomy from November 2017 to May 2021 were retrospectively analyzed. There were 46 males and 19 females. The average age was (56.6±14.1) years. The mean body mass index was (25.7±3.3) kg/m2. The tumors located in the left kidney in 30 cases and the right kidney in 35 cases. The ECOG score was 0 in 59 patients and 1 in 6 patients. The mean maximum diameter of the tumors was (2.3±1.0) cm(1.0-5.0 cm). According to R.E.N.A.L. scoring, 41 cases were of low difficulty (4-6 points), 23 cases of medium difficulty (7-9 points) and 1 case of high difficulty (10-12 points). The renal tumors were ablated by laparoscopic microwave ablation, then followed by partial nephrectomy. Postoperative complications were observed and the prognosis was assessed by CT or MRI. Results: The mean duration of operation was (76.6±19.4) min (40-120 min). The median intraoperative blood loss was 20 ml(5-50 ml). The median duration of postoperative hospitalization was 4 d(3-6 d). Complications of Clavien grade Ⅰ were found in 11 patients (fever, nausea and vomiting, lumbar pain), and no complications were grade Ⅱ or above. Postoperative pathology showed that no positive margin was found, and 46 cases of clear cell renal cell carcinoma (AJCC stage: T1a stage 42 cases, T1b stage 4 cases; WHO/ISUP classification: 21 cases of grade 1, 23 cases of grade 2, 2 cases of grade 3); 2 cases of type 1 papillary renal cell carcinoma (stage T1a, grade 1); 1 case of type 2 papillary renal cell carcinoma (T1b stage, grade 2); 2 cases of renal chromophobe carcinoma (all stage T1a); 1 case of low-grade malignant potential multilocular cystic renal tumor; 2 cases of adenocarcinoma (combined with the postoperative history of rectal cancer, metastasis was considered); 6 cases of renal angiomyolipoma; 2 cases of eosinophiloma; 1 case of papillary adenoma; 1 case of benign renal cyst and 1 case of renal hemangioma with calcification. The median follow-up was 24 months (1-42 months). Sixty-three patients survived and two died (one due to heart disease and one due to metastatic colorectal cancer). According to postoperative imaging, there were no signs of tumor recurrence or metastasis in other cases. Blood tests were performed regularly, and no significant abnormalities occurred. Conclusions: The safety and efficacy of laparoscopic microwave ablation combined with partial nephrectomy for the treatment of renal tumor is satisfactory, such as less intraoperative bleeding, fewer complications, less effect on renal function and postoperative pathology, providing a potential option for renal tumor treatment.

[Efficacy and safety of ruxolitinib in the salvage treatment of chronic graft versus-host disease].

Objective: To investigate the efficacy and safety of low-dose Ruxolitinib in the treatment of patients with chronic graft-versus-host disease (cGVHD) and refractory to the first-line and/or second-line drugs after allogeneic hematopoietic stem cell transplantation. Methods: The clinical data was retrospectively analyzed of patients diagnosed with cGVHD in Anhui Provincial Hospital from July 9, 2018 to May 23, 2019. They were refractory to first-line and second-line drugs and were given a low-dose of Ruxolitinib (a dose of 5 mg twice daily if body weight ≥ 25 kg and 2.5 mg twice daily if body weight<25 kg). There was 2.5 mg reduction per week or every two weeks if the condition improved until withdrawal. The efficacy and safety of Ruxolitinib were retrospectively analyzed weekly or biweekly. If the condition improved, the dosage would be reduced by 2.5 mg weekly or biweekly until discontinuance. Results: A total of 47 patients were included in the study,and the median time of taking Ruxolitinib was 55 (21-154) days. The median time of taking effect was 14(7-28) days. The overall response rate was 87.2% (41/47). The complete response rate was 63.8% (30/47) and the partial response rate was 23.4%(11/47). Among them, 13 cases were mild and the overall response rate was 100%(13/13). Twenty one cases were moderate and the overall response rate was 90.5%(19/21). Thirteen cases were severe and the overall response rate was 69.2%(9/13). The highest overall response rate of all organs the was 100% in the gastrointestinal tract (7/7), and it was 95.8%(23/24) for the skin, 83.3%(5/6) for the liver and 76.9%(10/13) for the lung. The highest rate of complete organ response was 95.8% for skin. Eight patients (17%) developed cytopenia, of which 2(4.2%) were with a decrease of 3-4 degree hemoglobin. Recrudescence of cytomegalovirus occurred in 3 patients (6.4%). After withdrawal of Ruxolitinib, 6 patients (12.7%) had recurrence of cGVHD. The median time to relapse was 35.5(7-90) days. All of their conditions were improved after addition of Ruxolitinib. The median time of response was 7(5-14) days. The median follow-up was 208(33-412) days. Three patients(6.4%) died, and all of them died of severe pulmonary infection. Three patients (6.4%) had relapse of primary disease. The 6-month overall survival rate was 95.7%. Conclusion: Low-dose Ruxolitinib has good efficacy and safety in the treatment of cGVHD.

[Chromosomal abnormalities in spontaneous miscarriage specimens detected by combinatorial probe anchor synthesis-based high-throughput low coverage whole genome sequencing].

Objective: To evaluate the application of combinatorial probe anchor synthesis (cPAS)-based high-throughput low coverage whole genome sequencing in chromosomal aberration detection in spontaneous miscarriage. Methods: From September 2015 to May 2017, spontaneous miscarriage samples were collected from Inner Mongolia Maternal and Child Health Care Hospital. Those samples were further analyzed with two independent methods, fluorescence in situ hybridization (FISH) and low coverage whole genome sequencing on the BGISEQ-500 high-throughput platform. The performance of low coverage whole genome sequencing was assessed by comparing to FISH results. Results: In 595 spontaneous miscarried specimens, low coverage whole genome sequencing revealed 144 cases (24.2%, 144/595) chromosomal abnormalities, of which a subset of 137 cases (23.0%, 137/595) were detected as aneuploidies, 2 cases (0.3%, 2/595) as mosaicisms and 5 cases (0.8%, 5/595) as copy number variation (≥5 Mb). Conclusion: cPAS-based high-throughput low coverage whole genome sequencing is a reliable method in detecting chromosomal aberrations inspontaneous abortion tissues, including chromosome aneuploidies, mosaicisms and copy number variation (≥5 Mb).

Clinical value of fluid bolus contrast flow meter during hysterosalpingography.

The purpose of this study was to investigate the clinical value of the fluid bolus contrast flow meter during hysterosalpingography. Hysterosalpingography information of 342 cases, which included a manual handset group of 213 cases and a bolus instrument group of 129 cases were reviewed. Comparative analysis was used to compare the two groups in order to assess the clinical adverse reactions, contrast agent reflux, and image quality. In the instrument bolus group compared with the manual handset group, the clinical adverse reactions decreased from 75.12 to 31.78% (P < 0.001); the backflow phenomenon of the contrast agent decreased from 13.62 to 3.10% (P < 0.01); and image quality significantly improved, with the A class film rate increasing from 54.46 to 68.99% (P < 0.01) and the C class film rate decreasing from 8.92 to 2.33% (P < 0.05). The use of a contrast bolus through the liquid inlet of the hysterosalpingography instrument can provide fully dynamic observation, reducing the contrast agent reflux and adverse reactions as well as improving the image quality and diagnostic accuracy. In addition, the medical staff is not subjected to radiographic radiation. Therefore, it is a safe and reliable imaging method.

Management of Meloidogyne incognita on tomato with endophytic bacteria and fresh residue of Wasabia japonica.

AIMS: To characterize the nematicidal endophytic bacteria (NEB) of Wasabia japonica (wasabi) and evaluated the control efficacies of promising NEB as well as fresh wasabi residue (FWR) against Meloidogyne incognita on tomato. METHODS AND RESULTS: By in vitro bioassay, 53 NEB strains showing nematicidal efficacies of >50% against J2 of M. incognita were isolated from wasabi. Basing on 16S rRNA gene sequences, these NEB were identified into 18 species of 11 genera. In greenhouse, incorporation of selected NEB culture or FWR into potted soil significantly reduced infection of M. incognita on tomato. Treating tomatoes with either FWR or NEB of Raoultella terrigena RN16 and Pseudomonas reinekei SN21 in the field yielded excellent control efficacies against M. incognita, especially the combinations of FWR with either R. terrigena RN16 or Ps. reinekei SN21 at doses of 50 g plus 100 ml per plant or more. CONCLUSIONS: The results established that R. terrigena RN16 and Ps. reinekei SN21 applied separately or combined with FWR have the potential to provide bioprotection agents against M. incognita. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides novel way for disease management using combination of endophyte and host residue.

Behavioral training-induced c-Fos expression in the rat nucleus basalis of Meynert during aging.

The present study investigated the behavioral training-induced c-Fos expression in the nucleus basalis of Meynert (nbM) in differently aged rats. This study demonstrated that the c-Fos expression in nbM was significantly increased and the peak occurred at 2 h after dark-avoidance training. Although the increase of c-Fos expression was also observed after pseudotraining, the number of Fos-like immunoreactive neurons in pseudotrained rats was significantly less than that in dark-avoidance trained rats at each time-point. This result suggested that c-Fos expression might be involved in learning and memory processes. In addition, all the pseudotraining-, training- and memory arousing-induced c-Fos expression was decreased with increasing age, and the decrease was more notable in trained and memory aroused rats. This suggested that the total number of nbM neurons and/or the sensitivity of nbM neurons to experimental manipulations, especially learning and memory performance, might reduce during aging.

Effect of intracerebralventricular injection of nitric oxide donor and nitric oxide synthase inhibitor on the spontaneous discharge of magnocellular neurons of paraventricular nucleus in the rat.

The effects of intracerebralventricular (icv) injection of nitric oxide (NO) donor and nitric oxide synthase (NOS) inhibitor on the spontaneous discharge of magnocellular neurons of paraventricular nucleus (PVN) of hypothalamus were investigated in urethane anaesthetized adult SD rats by using microelectrode extracellularly recording method. The results showed that icv injection of NO donor sodium nitroprusside (SNP) had dose-dependent inhibitory effects on vasopressin (VP) secreting units in PVN. Icv injection of NOS inhibitor N( )-nitro-L-arginine methyl ester (L-NAME) also inhibited all of the VP-secreting neurons examined. Both the drugs had no effect on almost all oxytocin (OT) secreting units. These results suggest that NO may differentially modulate the activities of OT and VP neurons.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of phospholipase A2 and fibrinolytic enzyme, two enzymes obtained from Chinese Agkistrodon blomhoffii Ussurensis venom.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) was used to analyze two enzymes, phospholipase A2 and fibrinolytic enzyme isolated from Chinese Agkistrodon blomhoffii Ussurensis venom. Using sinapinic acid as the matrix, positive ion mass spectra of the enzymes were obtained. In addition to the dominant protein [M + H]+ ions, multimeric and multiply charged ions were also observed in the mass spectra. The higher the concentration of the enzymes, the more multiply charged polymer and multimeric ions were detected. Our results indicate that MALDI-TOFMS can provide a rapid and accurate method for molecular weight determination of snake venom enzymes. Mass accuracies of 0.1 and 0.3% were achieved by analysis of highly dialyzed phospholipase A2 and fibrinolytic enzyme, and these results are much better than those obtained using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. MALDI-TOFMS thus provides a reliable method to determine the purity and molecular weight of these enzymes, which are of potential use as therapeutants.

[Effects of intracerebroventricular administration of norepinephrine on paraventricular neurosecretory cells].

Extracellular electrical activities of paraventricular nucleus (PVN) cells were recorded in anaesthetized adult rats by using glass microelectrodes. After antidromical identification of the magnocellular neurosecretory cells, the effects of intracerebroventricular (i.c.v.) injection of norepinephrine (NE) on such cells were observed. Of 49 neurons of antidromic stimulation, phasic, fast continuous and slowly irregularly. firing units constituted 42.9%, 36.7%, and 20.4% of the total population respectively. With i.c.v. injection, NE inhibited the activity of most phasically firing units, but enhanced that of most fast continuous and slowly irregular firing units. The inhibition effect of NE could be partially antagonized by i.c.v. injection of phentolamine (2 micrograms/microliters), showing that the effect is possibly mediated by alpha-receptor. The above findings indicate that NE plays different roles in different PVN magnocellular neurons having different patterns of firing activity.

Suppression of nociceptive responses in parafascicular neurons by stimulation of substantia nigra: an analysis of related inhibitory pathways.

A total of 166 neurons in parafascicular nucleus (PF) were studied, 85 from intact animals, 72 following dorsal spinal cord transection (D.Sp.C.X.), and 9 following complete transection of the spinal cord. Two patterns of nociceptive responses were identified following noxious stimulation and these responses were classified as 'nociceptive-on' and 'nociceptive-off' neurons, respectively. The effects of stimulating the substantia nigra (SNS) on the spontaneous and on the nociceptive evoked discharges were observed and compared in intact, D.Sp.C.X. and completely transected spinal cord rats. The results show that SNS significantly suppresses both the spontaneous and the nociceptive evoked discharges elicited by peroneal nerve stimulation. With an intact spinal cord, SNS suppressed both the spontaneous [-37 +/- 3.2% (P less than 0.05)] and the nociceptive evoked discharges [-52.8 +/- 2.8% (P less than 0.01)] of the 'nociceptive-on' cells respectively, while in the 'nociceptive-off' cells the same stimulation elicited an even more prominent suppression upon both discharges (-47.7 +/- 5.4%, P less than 0.01 and -64.9 +/- 5.0%, P less than 0.01), respectively. After D.Sp.C.X., the suppressive effects on the 'nociceptive-on' cells following SNS were diminished (-28.1 +/- 3.5% and -36.9 +/- 2.6%, respectively) but not abolished, while in the 'nociceptive-off' cells, the inhibitory effects on SNS were unchanged. In addition, the suppressive effects of SNS on the spontaneous activity of PF neurons in cases with completely cut spinal cords remains unchanged. These results suggest that SNS modulates the spontaneous and the noxious evoked responses of the PF neurons by way of supraspinal connections besides the previously described descending projecting pathways.