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Background: Entecavir and tenofovir disoproxil fumarate (TDF) are standard first-line treatments to prevent viral reactivation and hepatocellular carcinoma (HCC) in individuals chronically infected with the hepatitis B virus (HBV), but the long-term efficacy of the two drugs remains controversial. Also unclear is whether the drugs are effective at preventing viral reactivation or HCC recurrence after hepatectomy to treat HBV-associated HCC. This trial will compare recurrence-free survival, overall survival, viral indicators and adverse events in the long term between patients with HBV-associated HCC who receive entecavir or TDF after curative resection., Methods: This study is a randomized, open-label trial. A total of 240 participants will be randomized 1:1 into groups receiving TDF or entecavir monotherapy. The two groups will be compared in terms of recurrence-free and overall survival at 1, 3, and 5 years after surgery; adverse events; virological response; rate of alanine transaminase normalization; and seroreactivity at 24 and 48 weeks after surgery., Discussion: This study will compare long-term survival between patients with HBV-associated HCC who receive TDF or entecavir monotherapy. Numerous outcomes related to prognosis will be analyzed and compared in this study., Trial Registration: ClinicalTrials.gov NCT02650271. Registered on January 7, 2016., (© 2024. The Author(s).)

Objectives: To compare the short-term outcomes of unilateral biportal endoscopic lumbar interbody fusion (BLIF) and uniportal endoscopic lumbar interbody fusion (ULIF)., Methods: Sixty patients diagnosed with L4/5 spinal stenosis who underwent BLIF and ULIF were included (30 in each group). Clinical evaluation was performed preoperatively and postoperatively in the 1st week, 1st month, and 1st year. Factors such as the visual analogue score (VAS), Oswestry Disability Index (ODI), operative time, surgical complications, and radiological outcomes (fusion rate, screw loosening, and cage subsidence) were compared between the two groups., Results: All patients showed improved mean VAS and ODI at all three postoperative follow-ups, and no statistically significant differences were detected between the BLIF and ULIF groups. The mean operative time in the BLIF group was shorter than that in the ULIF group. Nerve root injury occurred in two patients in the BLIF group, while leakage of cerebrospinal fluid occurred in one patient in the ULIF group. All adverse events were treated adequately prior to discharge. The fusion rates with definite and probable grades were significantly higher in the BLIF group than that in the ULIF group. One case of cage subsidence with no screw loosening occurred in each group., Conclusion: Both BLIF and ULIF are safe and effective surgical techniques. Compared with ULIF, BLIF has the advantages of shorter operative time and a higher fusion rate. Other merits of BLIF include a wider surgical field, greater maneuverability of instruments, visibility during cage implantation, and transverse orientation of the cage., (© 2022. The Author(s).)

Background: LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years., Methods: LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 10 6 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy., Results: As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer., Conclusions: The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285., (© 2022. The Author(s).)

Objective: To evaluate the biomechanical influence after percutaneous endoscopic lumbar facetectomy in different diameters on segmental range of motion (ROM) and intradiscal pressure (IDP) of the relevant segments by establishing three dimensional finite element (FE) model., Methods: An intact L3-5 model was successfully constructed from the CT of a healthy volunteer as Model A (MA). The Model B (MB), Model C (MC) and Model D (MD) were obtained through facetectomy on L4 inferior facet in diameters 7.5 mm, 10 mm and 15 mm on MA for simulation. The ROM and IDP of L3/4 and L4/5 of four models were all compared in forward flexion, backward extension, left and right bending, left and right rotation., Results: Compared with MA, the ROM of L4/5 of MB, MC and MD all increased. MD changed more significantly than MB and MC in backward extension, right bending and right rotation. But that of MB and MC on L3/4 had no prominent change, while MD had a slight increase in backward extension. The IDP of MB and MC on L4/5 in six states was similar to MA, yet MD increased obviously in backward extension, right bending, left and right rotation. The IDP on L3/4 of MB and MC was resemble to MA in six conditions, nevertheless MD increased slightly only in backward extension., Conclusion: Compared with the facetectomy in diameters 7.5 mm and 10 mm, the mechanical effect brought by facetectomy in diameter 15 mm on the operating segment changed more significantly, and had a corresponding effect on the adjacent segments., (© 2021. The Author(s).)

Background: To investigate predictors of pathological invasiveness and prognosis of lung adenocarcinoma in patients with pure ground-glass nodules (pGGNs)., Methods: Clinical and computed tomography (CT) features of invasive adenocarcinomas (IACs) and pre-IACs were retrospectively compared in 641 consecutive patients with pGGNs and confirmed lung adenocarcinomas who had undergone postoperative CT follow-up. Potential predictors of prognosis were investigated in these patients., Results: Of 659 pGGNs in 641 patients, 258 (39.1%) were adenocarcinomas in situ, 265 (40.2%) were minimally invasive adenocarcinomas, and 136 (20.6%) were IACs. Respective optimal cutoffs for age, serum carcinoembryonic antigen concentration, maximal diameter, mean diameter, and CT density for distinguishing pre-IACs from IACs were 53 years, 2.19 ng/mL, 10.78 mm, 10.09 mm, and - 582.28 Hounsfield units (HU). Univariable analysis indicated that sex, age, maximal diameter, mean diameter, CT density, and spiculation were significant predictors of lung IAC. In multivariable analysis age, maximal diameter, and CT density were significant predictors of lung IAC. During a median follow-up of 41 months no pGGN IACs recurred., Conclusions: pGGNs may be lung IACs, especially in patients aged > 55 years with lesions that are > 1 cm in diameter and exhibit CT density > - 600 HU. pGGN IACs of < 3 cm in diameter have good post-resection prognoses.

Background: To study the outcome and experience of using metallic stents in treating patients with malignant ureteral obstruction (MUO)., Methods: Seventy-six patients with MUO were assigned to the metallic stent group (MSG) or the ordinary polymer stent group (OPSG) according to the different materials. The success rate of the operation, duration of operation, patency rate serum creatinine values ,postoperative complications and QOL scores were compared between the two groups., Results: In the OPSG and MSG, the success rates of the operation were 95.5% and 96.9%, respectively, and the durations of the operation were 20.6 ± 2.2 min and 50.9 ± 10.3 min (P < 0.01), respectively. There was no significant difference between the groups in serum creatinine values at 3 days after the operation (P > 0.05); however, the creatinine values at 3 days after the operation decreased significantly compared with those before the operation (P < 0.01). In the OPSG, there was no significant difference in creatinine values between 3 days and 6 months after operation, while the creatinine values 1 year after operation were increased significantly compared to those at 3 days after the operation (P < 0.05). In the MSG, there was no significant difference among creatinine values at different intervals (P > 0.05). The total rate of post-procedural complication was lower in the MSG than that in the OPSG(P < 0.05). There was no significant difference in the QOL score between the two groups before the operation (P > 0.05); however, the QOL scores at 6 months and 1 year after the operation were higher in the MSG than that in the OPSG(P < 0.05). In the MSG, there was no significant difference in the QOL score between preoperation and 6 months after surgery. Similarly, there was also no difference in the QOL score between 6 months after surgery and 1 year after surgery(P > 0.05). On the contrary, the differences of QOL score in the OPSG group were much significant between disparate time intervals (P < 0.05)., Conclusions: For patients with MUO who require long-term retention of the stent, metallic stents with longer indwelling time are superior to ordinary polymeric stents.

Background: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM)., Methods: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m 2 . LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10 6 cells/kg [range, 0.07 to 2.1 × 10 6 ]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group., Results: At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached., Conclusions: LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM., Trial Registration: ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.

Background: Extracorporeal shock wave lithotripsy (ESWL) is an effective therapeutic method used to treat patients with pancreatic stones. However, the anesthesia for this procedure has been underappreciated, with minimal reports of these procedures in certain case series with general or epidural anesthesia., Methods: A cohort of 60 patients who elected to undergo ESWL in order to treat pancreatic stones for the first time were randomly selected and divided into two groups. One group of patients received target controlled infusion (TCI) of remifentanil, while the other group of patients received TCI of remifentanil plus a bolus of flurbiprofen axetil (a cyclooxygenase inhibitor) (Rem group and Rem + Flu group, n = 30 for each group). The Dixon's up-and-down method was used to calculate the half maximum effective concentration (EC50) of remifentanil. Visual analogue scales of pain, Ramsay sedation scale, hemodynamic changes, and adverse events were also recorded., Results: The EC50 of remifentanil was calculated to be 4.0 ng/ml (95 % confidential interval: 3.84 ng/ml, 4.16 ng/ml) and 2.76 ng/ml (95 % confidential interval: 2.63 ng/ml, 2.89 ng/ml) in the Rem group and Rem + Flu group respectively (p < 0.001). Pain score was comparable between the two groups, while the Ramsay sedation scale was higher in the Rem group. Hemodynamic data showed that patients in the Rem group experienced higher mean arterial pressures and higher heart rates across the procedures. Patients in Rem group demonstrated a lower respiratory rate (p < 0.001) and a lower SpO2 (p = 0.001). Less adverse events occurred in Rem + Flu group, including a reduced respiratory depression requiring wake-up as well as reduced postoperative nausea and vomiting., Conclusion: Remifentanil plus flurbiprofen axetil provided satisfactory analgesia and sedation for ESWL of pancreatic stones with less adverse events. (Clinicaltrial.gov: NCT01998217 ; registered on November 19, 2013).

Background: Reproducibility is a fundamental requirement in scientific experiments. Some recent publications have claimed that microarrays are unreliable because lists of differentially expressed genes (DEGs) are not reproducible in similar experiments. Meanwhile, new statistical methods for identifying DEGs continue to appear in the scientific literature. The resultant variety of existing and emerging methods exacerbates confusion and continuing debate in the microarray community on the appropriate choice of methods for identifying reliable DEG lists., Results: Using the data sets generated by the MicroArray Quality Control (MAQC) project, we investigated the impact on the reproducibility of DEG lists of a few widely used gene selection procedures. We present comprehensive results from inter-site comparisons using the same microarray platform, cross-platform comparisons using multiple microarray platforms, and comparisons between microarray results and those from TaqMan - the widely regarded "standard" gene expression platform. Our results demonstrate that (1) previously reported discordance between DEG lists could simply result from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion with a non-stringent P-value cutoff filtering, the DEG lists become much more reproducible, especially when fewer genes are selected as differentially expressed, as is the case in most microarray studies; and (3) the instability of short DEG lists solely based on P-value ranking is an expected mathematical consequence of the high variability of the t-values; the more stringent the P-value threshold, the less reproducible the DEG list is. These observations are also consistent with results from extensive simulation calculations., Conclusion: We recommend the use of FC-ranking plus a non-stringent P cutoff as a straightforward and baseline practice in order to generate more reproducible DEG lists. Specifically, the P-value cutoff should not be stringent (too small) and FC should be as large as possible. Our results provide practical guidance to choose the appropriate FC and P-value cutoffs when selecting a given number of DEGs. The FC criterion enhances reproducibility, whereas the P criterion balances sensitivity and specificity.

Background: Fibrates are a unique hypolipidemic drugs that lower plasma triglyceride and cholesterol levels through their action as peroxisome proliferator-activated receptor alpha (PPARalpha) agonists. The activation of PPARalpha leads to a cascade of events that result in the pharmacological (hypolipidemic) and adverse (carcinogenic) effects in rodent liver., Results: To understand the molecular mechanisms responsible for the pleiotropic effects of PPARalpha agonists, we treated mouse primary hepatocytes with three PPARalpha agonists (bezafibrate, fenofibrate, and WY-14,643) at multiple concentrations (0, 10, 30, and 100 microM) for 24 hours. When primary hepatocytes were exposed to these agents, transactivation of PPARalpha was elevated as measured by luciferase assay. Global gene expression profiles in response to PPARalpha agonists were obtained by microarray analysis. Among differentially expressed genes (DEGs), there were 4, 8, and 21 genes commonly regulated by bezafibrate, fenofibrate, and WY-14,643 treatments across 3 doses, respectively, in a dose-dependent manner. Treatments with 100 muM of bezafibrate, fenofibrate, and WY-14,643 resulted in 151, 149, and 145 genes altered, respectively. Among them, 121 genes were commonly regulated by at least two drugs. Many genes are involved in fatty acid metabolism including oxidative reaction. Some of the gene changes were associated with production of reactive oxygen species, cell proliferation of peroxisomes, and hepatic disorders. In addition, 11 genes related to the development of liver cancer were observed., Conclusion: Our results suggest that treatment of PPARalpha agonists results in the production of oxidative stress and increased peroxisome proliferation, thus providing a better understanding of mechanisms underlying PPARalpha agonist-induced hepatic disorders and hepatocarcinomas.