Leg-Length Change After Unilateral Unicompartmental Knee Arthroplasty in Varus Knee and Its Clinical Implications.

BACKGROUND: To explore the magnitude of leg-length change after the unilateral index unicompartmental knee arthroplasty (UKA) in varus knee and its influence on clinical outcomes. METHODS: A total of 114 patients with bilateral knee osteoarthritis who underwent unilateral UKA from June 2015 to June 2017 were included and followed up for at least 2 years. The leg length and hip-knee angle were measured on full-length standing films before and after the surgery. Flexion contracture was evaluated using a goniometer with the patient in the standing position preoperatively and postoperatively. Hospital for Special Surgery scores, perceived leg-length discrepancy (pLLD), the occurrence, and the time interval of subsequent contralateral knee arthroplasty were recorded and analyzed. RESULTS: The average leg length increased after UKA was 9.39 ± 11.24 mm (range -21.00 to 33.79 mm), and 90 (78.9%) patients showed an increase in the leg length. 35 patients had LLD (defined as ≥10 mm), and 25 presented pLLD preoperatively; 25 patients had LLD, and 45 were suspected with pLLD postoperatively. At the last follow-up, 26 patients underwent subsequent contralateral knee arthroplasty. Postoperative LLD and pLLD were not associated with Hospital for Special Surgery scores of UKA but associated with subsequent contralateral knee arthroplasty. CONCLUSIONS: LLD and pLLD were common in patients both before and after UKA. Most patients showed leg lengthening after UKA. Postoperative LLD and pLLD were not associated with functional scores but associated with a subsequent contralateral knee arthroplasty.

[Analysis of the efficacy and prognostic factors of 1 637 esophageal cancer patients treated with intensity-modulated radiotherapy].

Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

Hepatic Tm6sf2 overexpression affects cellular ApoB-trafficking, plasma lipid levels, hepatic steatosis and atherosclerosis.

The human transmembrane 6 superfamily member 2 (TM6SF2) gene has been implicated in plasma lipoprotein metabolism, alcoholic and non-alcoholic fatty liver disease and myocardial infarction in multiple genome-wide association studies. To investigate the role of Tm6sf2 in metabolic homeostasis, we generated mice with elevated expression using adeno-associated virus (AAV)-mediated gene delivery. Hepatic overexpression of mouse Tm6sf2 resulted in phenotypes previously observed in Tm6sf2-deficient mice including reduced plasma lipid levels, diminished hepatic triglycerides secretion and increased hepatosteatosis. Furthermore, increased hepatic Tm6sf2 expression protected against the development of atherosclerosis in LDL-receptor/ApoB48-deficient mice. In cultured human hepatocytes, Tm6sf2 overexpression reduced apolipoprotein B secretion and resulted in its accumulation within the endoplasmic reticulum (ER) suggesting impaired ER-to-Golgi trafficking of pre-very low-density lipoprotein (VLDL) particles. Analysis of two metabolic trait-associated coding polymorphisms in the human TM6SF2 gene (rs58542926 and rs187429064) revealed that both variants impact TM6SF2 expression by affecting the rate of protein turnover. These data demonstrate that rs58542926 (E167K) and rs187429064 (L156P) are functional variants and suggest that they influence metabolic traits through altered TM6SF2 protein stability. Taken together, our results indicate that cellular Tm6sf2 level is an important determinant of VLDL metabolism and further implicate TM6SF2 as a causative gene underlying metabolic disease and trait associations at the 19p13.11 locus.

Long-term renal outcomes in multi-ethnic Southeast Asians with lupus nephritis: a retrospective cohort study.

BACKGROUND: Renal involvement is common among Asians with systemic lupus erythematosus and long-term renal outcomes have been described in homogeneous Caucasian and East Asian populations with lupus nephritis, but data are scarce for other ethnicities. AIM: To evaluate the incidence and risk factors for progressive chronic kidney disease (CKD) in multi-ethnic Southeast Asians with lupus nephritis. METHODS: This is a single-centre retrospective cohort study of adults with biopsy-proven lupus nephritis diagnosed between May 2001 and May 2009. Demographic and clinical data were retrieved from electronic medical records. Patients were excluded if baseline comorbid, renal function or pharmacotherapy data were incomplete or if they default follow-up within 3 months from time of diagnosis. Primary outcome was progressive CKD, defined by end-stage renal disease or persistent doubling of serum creatinine or reduction in eGFR ≥50% for ≥3 months from baseline. RESULTS: We studied 113 patients with newly diagnosed biopsy-proven lupus nephritis. Median age was 42 (interquartile range 29-52) years; the majority were Chinese (76%; Malay 13% and others 11%) and female (81%). Two-thirds had International Society of Nephrology and Renal Pathology Society Class III or IV nephritis; serum creatinine was 86 (67-125) µmol/L with heavy proteinuria (6.3 (2.5-12.2) g/g creatinine). Median follow-up was 110 (83-142) months. Remission (partial and complete) occurred in 96% at 3.1 (1.6-5.2) months after diagnosis. Among patients who achieved remission, 56% had disease relapse at 19.0 (6.0-40.2) months after remission. Patients with progressive CKD (n = 13, 11%) had lower baseline CKD Epidemiology Collaboration estimated glomerular filtration rate (37.3 (16.5-82.0) vs 79.4 (57.5-101.0) mL/min/1.73 m2 , P = 0.03) and higher chronicity index (5 (3-6) vs 3 (2-3), P = 0.04) than those who did not. Remission, early remission within 6 months, complete remission and non-relapse were less frequently associated with progressive CKD (P < 0.01). CONCLUSION: Multi-ethnic Southeast Asians with biopsy-proven lupus nephritis had high remission rates and low incidence of progressive CKD. Progressive CKD was associated with poorer baseline renal function, higher histological chronicity index, failure to achieve remission and occurrence of relapse.

[Prognostic value of pretreatment neutrophil-to-lymphocyte ratio (NLR) in locally advanced non-small cell lung cancer patients treated with thoracic radiation].

Objective: The aim of this retrospective study was to evaluate the prognostic significance of pretreatment Neutrophil-to-Lymphocyte Ratio(NLR) in locally advanced non-small cell lung cancer(NSCLC) patients treated with thoracic radiotherapy. Methods: We retrospectively analyze 420 patients who received thoracic radiotherapy alone, sequential chemoraiotherapy or concurrent chemoradiotherapy for locally advanced stage NSCLC from January 2007 to December 2010 of our hospital. The patients were divided into two groups (high NLR group and low NLR group) with appropriate cutoff point using the receiver operating characteristic (ROC) curve method. The survival curve was established by Kaplan-Meier method. The Log-rank test was used to compare the survival of the two NLR groups and the multivariate analysis was carried out by Cox regression model. Results: Among the 420 patients, 99 received radiotherapy alone, 139 received sequential chemoradiotherapy and 182 received concurrent chemoradiotherapy. 345 patients died and 75 were still alive. The median follow-up time was 5.2 years and the median overall survival was 22 months. The cut-off value of pretreatment NLR was 2.1. The 5-year PFS and OS rates in high NLR group and low NLR group were 10.6% vs 15.7% (P=0.033) and 15.5% vs 22.7% (P=0.012). Multivariate analysis confirmed that pretreatment NLR (hazard ratio 1.06, P=0.041) was independent prognostic factor of OS. Conclusions: Our study revealed that the pretreatment NLR is the independent prognostic factor of OS in patients with locally advanced stage NSCLC treated with thoracic radiotherapy. However, NLR is still greatly influenced by patient's condition and treatment which needs further research.

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial.

Background: The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients and methods: Patients were randomly received 60-66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1-5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. Results: A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%-28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55-1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). Conclusion: EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. Trial registration ID: NCT01494558.

[IMRT-based preoperative neoadjuvant chemoradiotherapy for thoracic esophageal squamous cell carcinoma (ESCC): an analysis of outcome and prognosis].

OBJECTIVE: To analyze the outcome and prognostic factors of IMRT-based preoperative neoadjuvant chemoradiotherapy in patients with thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Clinical data of 62 patients with thoracic ESCC who received IMRT-based neoajuvant chemoradiotherapy from January 2009 to January 2015 were retrospectively analyzed. The radiation therapy was given 1.8-2 Gy/fraction per day over 5 days per week with 6 MV X-rays, and then all patients underwent esophagectomy and lymphadenectomy. RESULTS: Among the 62 patients, the R0 resection rate was 96.8%. Twenty (32.3%) patients achieved pCR and 56 (90.3%) cases got down-staging. Grade Ⅲ marrow suppression and esophagitis were seen in 8 (12.9%) and 2 (3.2%) patients, respectively. Eleven (17.7%) patients experienced postoperative complications and three died. The median follow-up was 27 months. The 1-, 3- and 5-year overall survival rates were 88.0%, 63.3% and 44.2%, respectively, with a corresponding disease-free survival rate of 68.1%, 54.8%, and 43.9%, respectively.The univariate analysis showed that pre-treatment stage Ⅱ, down-staging, T/N pCR, good tumor response to neoadjuvant chemoradiotherapy, pN0 and R0 resection were favorable prognostic factors (P<0.05). The multivariate analyses indicated that pre-treatment stage was an independent prognostic factor. CONCLUSIONS: For patients with thoracic ESCC, IMRT-based neoadjuvant chemoradiotherapy followed by surgery can achieve a higher R0 resection rate, down-staging rate, higher pCR rate, and a better tolerance. The incidence of postoperative complications is low. Pre-treatment stage, down-staging, pathological tumor response, lymph node status and R0 resection results are prognostic factors, and the pre-treatment stage is an independent prognostic factor.

[Technical advancement improves survival in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiotherapy].

OBJECTIVE: This study aimed to evaluate the impact of technical advancement of radiation therapy in patients with LA-NSCLC receiving definitive radiotherapy (RT). METHODS: Patients treated with definitive RT (≥50 Gy) between 2000 and 2010 were retrospectively reviewed. Overall survival (OS), cancer specific survival (CSS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were calculated and compared among patients irradiated with different techniques. Radiation-induced lung injury (RILI) and esophageal injury (RIEI) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0 (NCI-CTCAE 3.0). RESULTS: A total of 946 patients were eligible for analysis, including 288 treated with two-dimensional radiotherapy (2D-RT), 209 with three-dimensional conformal radiation therapy (3D-CRT) and 449 with intensity-modulated radiation therapy (IMRT) respectively. The median follow-up time for the whole population was 84.1 months. The median OS of 2D-RT, 3D-CRT and IMRT groups were 15.8, 19.7 and 23.3 months, respectively, with the corresponding 5-year survival rate of 8.7%, 13.0% and 18.8%, respectively (P<0.001). The univariate analysis demonstrated significantly inferior OS, LRPFS, DMFS and PFS of 2D-RT than those provided by 3D-CRT or IMRT. The univariate analysis also revealed that the IMRT group had significantly loger LRPFS and a trend toward better OS and DMFS compared with 3D-CRT. Multivariate analysis showed that TNM stage, RT technique and KPS were independent factors correlated with all survival indexes. Compared with 2D-RT, the utilization of IMRT was associated with significantly improved OS, LRPFS, DMFS as well as PFS. Compared with 3D-CRT, IMRT provided superior DMFS (P=0.035), a trend approaching significance with regard to LRPFS (P=0.073) but no statistically significant improvement on OS, CSS and PFS in multivariate analysis. The incidence rates of RILI were significantly decreased in the IMRT group (29.3% vs. 26.6% vs.14.0%, P<0.001) whereas that of RIET rates were similar (34.7% vs. 29.7% vs. 35.3%, P=0.342) among the three groups. CONCLUSIONS: Radiation therapy technique is a factor affecting prognosis of LA-NSCLC patients. Advanced radiation therapy technique is associated with improved tumor control and survival, and decreased radiation-induced lung toxicity.

Lipase maturation factor 1 (lmf1) is induced by endoplasmic reticulum stress through activating transcription factor 6α (Atf6α) signaling.

Lipase maturation factor 1 (Lmf1) is a critical determinant of plasma lipid metabolism, as demonstrated by severe hypertriglyceridemia associated with its mutations in mice and human subjects. Lmf1 is a chaperone localized to the endoplasmic reticulum (ER) and required for the post-translational maturation and activation of several vascular lipases. Despite its importance in plasma lipid homeostasis, the regulation of Lmf1 remains unexplored. We report here that Lmf1 expression is induced by ER stress in various cell lines and in tunicamycin (TM)-injected mice. Using genetic deficiencies in mouse embryonic fibroblasts and mouse liver, we identified the Atf6α arm of the unfolded protein response as being responsible for the up-regulation of Lmf1 in ER stress. Experiments with luciferase reporter constructs indicated that ER stress activates the Lmf1 promoter through a GC-rich DNA sequence 264 bp upstream of the transcriptional start site. We demonstrated that Atf6α is sufficient to induce the Lmf1 promoter in the absence of ER stress, and this effect is mediated by the TM-responsive cis-regulatory element. Conversely, Atf6α deficiency induced by genetic ablation or a dominant-negative form of Atf6α abolished TM stimulation of the Lmf1 promoter. In conclusion, our results indicate that Lmf1 is an unfolded protein response target gene, and Atf6α signaling is sufficient and necessary for activation of the Lmf1 promoter. Importantly, the induction of Lmf1 by ER stress appears to be a general phenomenon not restricted to lipase-expressing cells, which suggests a lipase-independent cellular role for this protein in ER homeostasis.

TNFR2 and IL-12 coactivation enables slanDCs to support NK-cell function via membrane-bound TNF-α.

Human blood NK cells exert strong cytotoxicity against transformed cells and produce different cytokines and chemokines with an important role in modulating immune responses. However, the nature of NK-cell function depends on NK-cell interaction with other immune cells. One type of immune cells that communicate with NK cells are 6-sulfo LacNAc DCs (slanDCs), which comprise a major subpopulation of proinflammatory human blood DCs. In this study, we investigated the molecular mechanisms by which slanDCs interact with NK cells. Our in vitro studies demonstrate that LPS-stimulated slanDCs enhance activation and function of NK cells essentially via membrane-bound TNF-α (mTNF-α). LPS stimulation upregulates expression of mTNF-α in slanDCs, and surface TNF receptor 2 (TNFR2) is upregulated on NK cells after coincubation with slanDCs. IL-12 secreted by slanDCs increases surface expression of TNFR2 in NK cells. TNFR2 signaling in NK cells leads to activation of NF-kB, a transcription factor for cytokines such as GM-CSF. GM-CSF provided by NK cells is responsible for enhancing IL-12 secretion in slanDCs. In conclusion, TNFR2 and IL-12 signaling, which support one another, enables slanDCs to enhance NK-cell function through mTNF-α, thereby regulating immune responses.

Results and prognostic factors of 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy for esophageal carcinoma.

The aim of this study was to summarize the outcomes and prognostic factors of 3-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for esophageal carcinoma in our institute. Five hundred ninety-two patients received radiotherapy for esophageal carcinoma (123 with 3D-CRT, 469 with IMRT) from January 2002 to March 2012. Three hundred sixty patients received radiotherapy alone and 232 patients received radiotherapy and chemotherapy. The endpoints were overall survival (OS), progression-free survival (PFS). Kaplan-Meier analysis was used to calculate endpoints, the log-rank test for univariate analysis, and multivariate analysis to identify independent prognostic factors. The median follow-up time was 22.6 months and the median dose was 60 Gy. The 1-year OS, PFS were 65.3%, 52.1%; the 3-year OS, PFS were 34.0%, 28.0%; and the 5-year OS, PFS were 23.5%, 19.6%. The median OS was 20 months (95% CI: 17.9-22.1 months) and the median PFS was 14 months (95% CI: 11.8-16.2 months). Univariate analysis indicated that sex, N-stage, M-stage, TNM stage, radiotherapy dose, weight loss before treatment, smoking, and drinking affected OS and PFS (p < 0.05 for all). T-stage affected OS (p = 0.042), but no significant influence on PFS (p = 0.101). The independent prognostic factors for better OS and PFS were early clinical TNM stage, high radiotherapy dose, and female sex (p < 0.05 for all). The results of esophageal carcinoma patients treated with 3D-CRT and IMRT with or without chemotherapy were promising. Clinical TNM stage, radiotherapy dose and sex were the independent prognostic factors for OS and PFS.

The interrelationship between cholinergic pathway in the magnocellular paraventricular nucleus and natriuresis.

The central nervous system is known to play important roles in the regulation of renal sodium excretion. The present study was designed to reveal the interrelationship between cholinergic pathway in the magnocellular paraventricular nucleus (PVN) and the natriuresis induced by brain cholinergic stimuli. The results indicated that urinary sodium excretion was significantly increased at 40 min after intracerebroventricular (ICV) injection of carbachol (CBC). Immunohistochemical studies showed that CBC increased choline acetyltransferase-immunoreactivity (ChAT-IR) in the magnocellular PVN and renal proximal convoluted tubule (PCT), respectively. After pretreatment with atropine, urinary sodium excretion was significantly reduced, and carbachol-increased ChAT-IR in the magnocellular PVN and PCT was also significantly decreased. These results suggested that brain cholinergic stimuli induced the natriuresis and increased the activity of cholinergic neurons in the magnocellular PVN and cholinergic system in the PCT. The blockade of muscarinic receptor completely abolished the natriuresis and partially inhibited carbachol-exerted stimulatory effects in the magnocellular PVN and PCT. To summarize, brain cholinergic pathway and peripheral cholinergic system in kidney were found to contribute to the natriuresis following brain cholinergic stimulation. Our findings revealed novel evidence that PVN was involved in the natriuresis via humoral mechanisms.

Effects of different doses of remimazolam on hemodynamics during general anesthesia in patients with septic shock.

OBJECTIVE: The stability of hemodynamics plays a vital role in the process of anesthesia induction for patients with septic shock. As a new-type benzodiazepine, remimazolam has numerous advantages, including rapid induction, rapid recovery, stable hemodynamics, and mild respiratory depression. Nevertheless, reports about the effects of remimazolam on hemodynamics in patients with septic shock are still limited. The study aimed to evaluate the effects that different doses of remimazolam have on hemodynamics in inducing general anesthesia in patients with septic shock. PATIENTS AND METHODS: Admitted to the intensive care unit of our hospital from January 2023 to June 2023, 75 patients with septic shock caused by acute appendicitis-induced sepsis were selected as observation subjects. They were randomly assigned to receive low-dose [0.2 mg/(kg·h)], medium-dose [0.3 mg/(kg·h)], and high-dose [0.4 mg/(kg·h)] remimazolam by using a random number table, with 25 patients in each group. Their intraoperative conditions were recorded, including operation duration, intraoperative hemorrhage volume, intraoperative transfusion volume, and decannulation time. Hemodynamic parameters, including mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), and stoke volume index (SVI) were collected at seven-time points (T0: before induction; T1: before intubation; T2: after intubation; T3: the start of operation; T4: 15 min after operation; T5: 30 min after operation; T6: the end of operation). We also compared hepatic and renal function indexes, including blood urea nitrogen (BUN), serum creatinine (sCr), procalcitonin (PCT), white blood cells (WBC), tumor necrosis factor-α2 (TNF-α2), and Interleukin-6 (IL-6), of the three groups of patients before operation and 1, 3, 5, 7 days after operation. In addition, the incidence of adverse reactions in the three groups was recorded and compared. RESULTS: During remimazolam induction, the number of patients with intraoperative need for rescue remimazolam in the medium-dose and high-dose groups was significantly lower than in the low-dose group (p < 0.05). In terms of hemodynamic indexes, MAP in the high-dose group at T2 was lower than that at T0 (p < 0.05), and MAP at T2 was significantly lower in the high-dose group than that in the medium-dose group (p < 0.05). Furthermore, MAP at T4 in the medium-dose and high-dose groups declined compared with the low-dose group (p < 0.05). There were no significant differences in HR, CI, and SVI at different time points among the three groups (p > 0.05), but levels of HR and SVI decreased and CI increased after anesthesia compared with those before operation. Additionally, in comparison with the levels before operation, levels of sCR, BUN, PCT, WBC, TNF-α, and IL-6 were higher on postoperative days 1, 3 (p < 0.05) and lower on postoperative day 7 (p < 0.05). After the operation, both levels of BUN and sCR in the medium-dose and high-dose groups were lower than those in the low-dose group (p < 0.05). CONCLUSIONS: Remimazolam is safe and effective for inducing general anesthesia in patients with septic shock. Low, medium, and high doses of remimazolam can maintain a stable hemodynamic state, and the recovery of hepatic and renal function is certain to depend on the dose.

Transgenic expression and genetic variation of Lmf1 affect LPL activity in mice and humans.

OBJECTIVE: Lipoprotein lipase (LPL) is a principal enzyme in lipoprotein metabolism, tissue lipid utilization, and energy metabolism. LPL is synthesized by parenchymal cells in adipose, heart, and muscle tissues followed by secretion to extracellular sites, where lipolyic function is exerted. The catalytic activity of LPL is attained during posttranslational maturation, which involves glycosylation, folding, and subunit assembly within the endoplasmic reticulum. A lipase-chaperone, lipase maturation factor 1 (Lmf1), has recently emerged as a critical factor in this process. Previous studies demonstrated that loss-of-function mutations of Lmf1 result in diminished lipase activity and severe hypertriglyceridemia in mice and human subjects. The objective of this study is to investigate whether, beyond its role as a required factor in lipase maturation, variation in Lmf1 expression is sufficient to modulate LPL activity in vivo. METHODS AND RESULTS: To assess the effects of Lmf1 overexpression in adipose and muscle tissues, we generated aP2-Lmf1 and Mck-Lmf1 transgenic mice. Characterization of relevant tissues revealed increased LPL activity in both mouse strains. In the omental and subcutaneous adipose depots, Lmf1 overexpression was associated with increased LPL specific activity without changes in LPL mass. In contrast, increased LPL activity was due to elevated LPL protein level in heart and gonadal adipose tissue. To extend these studies to humans, we detected association between LMF1 gene variants and postheparin LPL activity in a dyslipidemic cohort. CONCLUSIONS: Our results suggest that variation in Lmf1 expression is a posttranslational determinant of LPL activity.

Concurrent erlotinib and radiotherapy for chemoradiotherapy-intolerant esophageal squamous cell carcinoma patients: results of a pilot study.

Concurrent chemoradiotherapy is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, a number of patients present intolerance to chemoradiotherapy because of advanced age or malnutrition. Erlotinib, an inhibitor of epidermal growth factor receptor tyrosine kinase, was shown to be effective in treating esophageal carcinoma, with mild toxicities. In this pilot study, we investigated the safety and efficacy of concurrent erlotinib and radiotherapy as an alternative treatment modality for esophageal carcinoma patients who are intolerant to chemoradiotherapy. Pathologically diagnosed esophageal squamous cell carcinoma patients who could not tolerate concurrent chemoradiotherapy were enrolled. All patients were treated with concurrent erlotinib and intensity-modulated radiation therapy. Erlotinib was given orally for 60 days (150 mg per day). Radiotherapy (total dose, 60 Gy) was given at dosages of 2 Gy for a total of 30 times. Immunohistochemical staining was performed to assess epidermal growth factor receptor expression. Toxicities were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). The overall survival, progression-free survival, and local-regional relapse-free survival were calculated using the Kaplan-Meier method. Between December 2007 and March 2011, 18 patients were enrolled. The median age was 71.5 years. Primary disease was stages II, III, and IV in 3, 8, and 4 patients, respectively. There were three patients with recurrent disease after radical surgery. The median follow-up time was 17.2 months. Grade 3 esophagitis and skin rash were observed in five (27.8%) and two (11.1%) patients, respectively. Radiation pneumonitis of grades 2 and 5 was observed in one patient each. No grade 3/4 impaired liver function or hematological toxicity was observed. At 1 month after radiotherapy, two (11.1%) patients achieved complete response, 11 (61.1%) patients achieved partial response, and 5 (27.8%) patients had stable disease. The median time of overall survival and progression-free survival was 21.1 and 12 months, respectively. Two-year overall survival, progression-free survival, and local-regional relapse-free survival were 44.4%, 38.9%, and 66.7%, respectively. Five of six patients examined for epidermal growth factor receptor had high expression levels (3+). The relationship between epidermal growth factor receptor expression and treatment outcomes could not be concluded. For esophageal squamous cell carcinoma patients who cannot tolerate chemoradiotherapy, concurrent erlotinib and radiotherapy are tolerable and effective. Valuable markers to predict the effect of erlotinib should be exploited in future studies.

Consensus for HER2 alterations testing in non-small-cell lung cancer.

Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein receptor with intracellular tyrosine kinase activity. Its alterations, including mutation, amplification and overexpression, could result in oncogenic potential and have been detected in many cancers such as non-small-cell lung cancer (NSCLC). Such alterations are, in general, considered markers of poor prognosis. Anti-HER2 antibody-drug conjugates, e.g. trastuzumab deruxtecan (T-DXd, DS-8201) and disitamab vedotin (RC48), were recently approved for HER2-positive breast and gastric cancers. Meanwhile, several HER2-targeted drugs, such as T-DXd, neratinib, afatinib, poziotinib and pyrotinib, have been evaluated in patients with advanced NSCLC, with several of them demonstrating clinical benefit. Therefore, identifying HER2 alterations is pivotal for NSCLC patients to benefit from these targeted therapies. Recent guidelines on HER2 testing were developed for breast and gastric cancer, however, and have not been fully established for NSCLC. The expert group here reached a consensus on HER2 alteration testing in NSCLC with the focus on clinicopathologic characteristics, therapies, detection methods and diagnostic criteria for HER2-altered NSCLC patients. We hope this consensus could improve the clinical management of NSCLC patients with HER2 alterations.

Nursing research in three regions in China: a bibliometric study.

OBJECTIVE: To analyse scientific papers published by Chinese authors in nursing journals included in the Science Citation Index Expanded and compare the published scientific papers from mainland China (ML), Taiwan (TW) and Hong Kong (HK). METHODS: All articles published in 62 journals that were related to nursing originating from ML, TW and HK from 1999 to 2008 were retrieved from the PubMed and Institute for Scientific Information (ISI) Web of Knowledge database. The total number of articles published in nursing journals, impact factors and citation reports and articles were estimated for quantity and quality comparisons. RESULTS: The number of articles from the three regions increased significantly from 1999 to 2008. There were 1015 articles in total from the three regions: ML (48), HK (414) and TW (553) in PubMed. In the ISI Web of Knowledge database, TW derived the highest total citations (1755 citations from 500 articles), followed by HK (1316 citations from 347 articles) and ML (158 citations from 55 articles). HK had the highest average citations of 3.79, followed by TW (3.51) and then ML (2.87). DISCUSSION: The difference between the quantity and quality of nursing research articles published in ML, TW and HK is significant, although the gap appears to be narrowing. Long-term job stresses, low levels of education and language barriers are likely the main factors. ML, TW and HK have the same culture and ethnicity. We expect that ML will benefit significantly from increased exchanges with TW and HK in nursing research and education. We also speculate that TW and HK will benefit from exchanges because ML may have diverse nursing problems.

Multiple Sessions of Entorhinal Cortex Deep Brain Stimulation in C57BL/6J Mice Increases Exploratory Behavior and Hippocampal Neurogenesis.

Deep brain stimulation (DBS) has been a medical intervention for a variety of nervous system diseases and mental diseases. The input of DBS in the entorhinal cortex (EC) regulates the neurophysiological activities in its downstream regions, such as the dentate gyrus (DG) area. EC DBS may play a role in the treatment of diseases through hippocampal neurogenesis. This study we examined the effect of multiple sessions of EC DBS on the regulation of hippocampal neurogenesis. 4-month-old male C57BL/6J mice received bilateral multiple sessions of EC DBS (130 Hz, 90 µs, 100 µA, 1 h/d, 21 days), and the DBS parameters used are close to the high-frequency DBS parameters in clinical studies. The open field test (OFT) was used to test the exploratory behavior of mice, and hippocampal neurogenesis was detected by immunofluorescence staining with anti-doublecortin (DCX). We found that multiple sessions of EC DBS were tolerated in C57BL/6J mice, significantly increased exploratory behavior and the number of DCX-positive neurons in the DG area.Clinical Relevance- Hippocampal neurogenesis may be part of the reason for DBS to improve memory, and the results of this study show that multiple sessions of EC DBS increases exploratory behavior and hippocampal neurogenesis, which is conducive to the application of DBS in nervous system diseases and mental diseases related to memory impairment.