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Hao-Kuang Wang,1– 3 Yu-Ting Su,4 Yu-Cheng Ho,3,5 Yung-Kuo Lee,6 Tian-Huei Chu,6 Kuang-Ti Chen,7 Cheng-Chun Wu3,5 1Department of Neurosurgery, E-DA Hospital, I-Shou University, Kaohsiung City, Taiwan; 2School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung City, Taiwan; 3Graduate Institute of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan; 4Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung City, Taiwan; 5School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan; 6Medical Laboratory, Medical Education and Research Center, Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan; 7Department of Veterinary Medicine, Nation Chung-Hsing University, Taichung City, TaiwanCorrespondence: Cheng-Chun Wu, School of Medicine, College of Medicine, I-Shou University, Kaohsiung City, Taiwan, Tel +886-7-6151100-7961, Fax +886-7-6155150, Email chengchunwu@isu.edu.twBackground: Stroke is a common cause of disability and mortality worldwide; however, effective therapy remains limited. In stroke pathogenesis, ischemia/reperfusion injury triggers gliosis and neuroinflammation that further activates matrix metalloproteinases (MMPs), thereby damaging the blood–brain barrier (BBB). Increased BBB permeability promotes macrophage infiltration and brain edema, thereby worsening behavioral outcomes and prognosis. Histone deacetylase 1 (HDAC1) is a repressor of epigenomic gene transcription and participates in DNA damage and cell cycle regulation. Although HDAC1 is deregulated after stroke and is involved in neuronal loss and DNA repair, its role in neuroinflammation and BBB damage remains unknown.Methods: The rats with cerebral ischemia were evaluated in behavioral outcomes, levels of inflammation in gliosis and cytokines, and BBB damage by using an endothelin-1-induced rat model with cerebral ischemia/reperfusion injury.Results: The results revealed that HDAC1 dysfunction could promote BBB damage through the destruction of tight junction proteins, such as ZO-1 and occludin, after stroke in rats. HDAC1 inhibition also increased the levels of astrocyte and microglial gliosis, tumor necrosis factor-alpha, interleukin-1 beta, lactate dehydrogenase, and reactive oxygen species, further triggering MMP-2 and MMP-9 activity. Moreover, modified neurological severity scores for the cylinder test revealed that HDAC1 inhibition deteriorated behavioral outcomes in rats with cerebral ischemia.Discussion: HDAC1 plays a crucial role in ischemia/reperfusion-induced neuroinflammation and BBB damage, thus indicating its potential as a therapeutic target.Keywords: HDAC1, stroke, blood-brain barrier, TNF-α, IL-1β, ROS, mNSS, cylinder test

Yu-Ying Wu,1,2 I-Fan Lin,1,3 Po-Yuan Chen,1,2 Cheng-Kai Lin,1,2 Cheng-Chun Wu,1 Cheng-Loong Liang,1,2 Yi-Che Lee,1,4 Chi-Wei Lin,1,5 Wei-Leng Chin,1,5 Hao Kuang Wang1,2,6 1School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 2Department of Neurosurgery, E-Da Hospital, Kaohsiung, Taiwan; 3Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan; 4Department of Nephrology, E-Da Hospital, Kaohsiung, Taiwan; 5Department of Family Medicine, E-Da Hospital, Kaohsiung, Taiwan; 6Department of Neurosurgery, E-Da Cancer Hospital, Kaohsiung, TaiwanCorrespondence: Hao Kuang WangDepartment of Neurosurgery, E-Da Hospital/ I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, TaiwanTel +866-975106080Email ed101393@gmail.comBackground: Osteoporotic fractures are a significant cause of morbidity and mortality affecting population worldwide. All guidelines recommended vertebral fracture assessment by dual-energy X-ray absorptiometry (DXA). This study aimed at evaluation of any associated benefits of screening with DXA in patients who had received vertebroplasty in Taiwan.Methods: Data were obtained from the National Health Insurance Research Database (NHIRD) in Taiwan. We retrospectively compared the data of patients, who were admitted for vertebroplasty, whether they received DXA screening or not. The outcomes of interest were recurrence of spinal fracture and mortality during a follow-up period of 10 years.Results: From this Taiwan national database, the screening rate of osteoporosis in patient who received vertebroplasty was 11.7%. The mean age in the non-DXA screened cohort (n=32,986) was 74.03± 12.21 years (71.98% female). In the DXA screened cohort (n=4361), the mean age was 76.43± 9.19 years (79.91% female). During the 10-year follow-up period, after matching, non-DXA patients had significantly higher mortality rates than their DXA counterparts, which were 42.37% and 37.73% (p-value < 0.0001), respectively. The re-fracture rates between non-DXA and DXA patients were not significantly different at 17.26% and 16.89% (p-value = 0.1766), respectively.Conclusion: The rate of DXA screening before patients receiving vertebroplasty was extremely low, at 11.7%. Our results showed that DXA screening before vertebroplasty in spinal fractures patients had lower mortality. From this national retrospective cohort study, routine screening of osteoporosis in spinal fracture patients can lead to reduction in mortality.Keywords: osteoporosis, vertebroplasty, DXA, mortality

Hao-Kuang Wang,1,2 Jui-Sheng Chen,1,3,4 Chien-Yu Hsu,1 Yu-Ting Su,5 Tzu-Ching Sung,2 Cheng-Loong Liang,1,6 Aij-Lie Kwan,3,7 Cheng-Chun Wu6 1Department of Neurosurgery, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan; 2School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Neurosurgery, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan; 5Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 6School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 7Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, TaiwanCorrespondence: Cheng-Chun WuSchool of Medicine, College of Medicine, I-Shou University, Kaohsiung, TaiwanTel +886-7-6151100-7961Fax +886-7-6155150Email chengchunwu@isu.edu.twIntroduction: Cerebral ischemia is a leading cause of disability and death worldwide. However, an effective therapeutic approach for the condition remains undiscovered. The previously proposed growth factor-based therapy has been inefficient due to its inability to pass through the blood–brain barrier. B355252, a newly developed small molecule, exhibited a potential neuroprotective effect in vivo. However, its exact efficacy in cerebral ischemia remains unclear.Methods: We adopt an endothelin-1 stereotaxic intracranial injection to induced cerebral ischemia in rat. We further conducted 2,3,5-triphenyltetrazolium chloride (TTC) staining, immunofluorescent staining, enzyme-linked immunosorbent assay (ELISA), and behavioral tests to evaluate the efficacy of B355252 in neuroprotection, anti-inflammation, and behavioral outcome improvements.Results: We identified that B355252 could protect ischemic neurons from neuronal loss by attenuating DNA damage, reducing ROS production and the LDH level, and preventing neuronal apoptosis. Moreover, inflammatory responses in astrocytic and microglial gliosis, as well as IL-1β and TNF-α levels, were ameliorated. Consequently, the behavioral outcomes of ischemic rats in neurologic responses and fore paw function recovery were improved.Discussion: Overall, our study verified the in vivo therapeutic potential of B355252. The study findings further support its application in the development of a therapeutic approach for stroke.Keywords: stroke, NGF, B355252, stroke, DNA damage, inflammation, mNSS, cylinder test

Fong-Yu Cheng,1 Yuan-Yow Chiou,2,3 Shih-Yuan Hung,4,5 Tsun-Mei Lin,6 Hao-Kuang Wang,7 Chi-Wei Lin,8 Hung-Hsiang Liou,9 Min-Yu Chang,5 Hsi-Hao Wang,5 Yi-Che Lee4,5,10 1Department of Chemistry, Chinese Culture University, Taipei, Taiwan; 2Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan; 3Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 5Division of Nephrology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 6Department of Laboratory Medicine, E-DA Hospital, Kaohsiung, Taiwan; 7Department of Neurosurgery, E-DA Hospital, Kaohsiung, Taiwan; 8Department of Medical Education, E-DA Hospital, Kaohsiung, Taiwan; 9Division of Nephrology, Department of Internal Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan; 10Division of Nephrology, Department of Internal Medicine, E-DA Dachang Hospital, Kaohsiung, TaiwanCorrespondence: Yi-Che LeeDivision of Nephrology, Department of Internal Medicine, E-DA Hospital/I-Shou University, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan, R.O.CTel +886-7-6150011 Ext 5121Email pipijer@gmail.comPurpose: Vitamin D3 is useful for the treatment of peritoneal dialysis (PD)-related peritoneal damage, but its side effects, such as hypercalcemia and vascular calcification, limit its applicability. Thus, we developed vitamin D-loaded magnetic nanoparticles (MNPs) and determined their therapeutic efficacy and side effects in vivo.Materials and Methods: Alginate-modified MNPs were combined with 1α, 25 (OH)2D3 to generate vitamin D-loaded nanoparticles. The particles were conjugated with an antibody against peritoneum-glycoprotein M6A (GPM6A). The particles’ ability to target the peritoneum was examined following intraperitoneal administration to mice and by monitoring their bio-distribution. We also established a PD animal model to determine the therapeutic and side effects of vitamin D-loaded MNPs in vivo.Results: Vitamin D-loaded MNPs targeted the peritoneum better than vitamin D3, and had the same therapeutic effect as vitamin D3 in ameliorating peritoneal fibrosis and functional deterioration in a PD animal model. Most importantly, the particles reduced the side effects of vitamin D3, such as hypercalcemia and body weight loss, in mice.Conclusion: Vitamin D-loaded MNPs could be an ideal future therapeutic option to treat PD-related peritoneal damage.Keywords: peritoneal dialysis, nanoparticles, vitamin D, fibrosis

Cheng-Kai Lin,1,2 Po-Yuan Chen,1,2 Yu-ying Wu,1,2 Cheng-Chun Wu,1 Han-Jung Chen,1,2 Cheng-Loong Liang,1,2 Yi-Che Lee,1,3 Chi-Wei Lin,1,4 Chao-Ming Hung,1,5,* Hao-Kuang Wang1,2,6,* 1School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 2Department of Neurosurgery, E-Da Hospital, Kaohsiung, Taiwan; 3Department of Nephrology, E-Da Hospital, Kaohsiung, Taiwan; 4Department of Family Medicine, E-Da Hospital, Kaohsiung, Taiwan; 5Department of General Surgery, E-Da Cancer Hospital, Kaohsiung, Taiwan; 6Department of Neurosurgery, E-Da Cancer Hospital, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Chao-Ming Hung; Hao-Kuang WangDepartment of Neurosurgery, E-Da Hospital/I-Shou University, No. 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 82445, TaiwanTel +866-975106080Email ed100647@edah.org.tw; ed101393@gmail.comBackground: Statin treatment improves clinical outcomes in patients with ischemic strokes, although there is no evidence regarding the safety of statin therapy in patients with intracerebral hemorrhage (ICH). This study aimed at evaluating the effects of continuing statin treatment after ICH.Methods: Data were obtained from the National Health Insurance Research Database in Taiwan. We retrospectively compared the data of patients with and without statin exposure after ICH. The outcomes of interest were recurrence of hemorrhagic stroke and mortality during a follow-up period of 10 years.Results: During the 10-year follow-up period, the mortality rate was 32.73% in the statin group and 42.77% in the non-statin group. Statin therapy in patients with acute ICH with dyslipidemia can decrease mortality.Conclusion: Statin therapy reduced the risk of 10-year mortality in patients who experienced acute hemorrhagic stroke.Keywords: statin, hemorrhagic stroke, mortality

Yi-Che Lee,1–3 Chih-Ting Huang,4 Fong-Yu Cheng,5 Shih-Yuan Hung,3,6 Tsun-Mei Lin,7 Yen-Chang Tsai,4 Chih-I Chen,8 Hao-Kuang Wang,9 Chi-Wei Lin,10 Hung-Hsiang Liou,11 Min-Yu Chang,3 Hsi-Hao Wang,3 Yuan-Yow Chiou4,12 1Division of Nephrology, Department of Internal Medicine, E-DA Dachang Hospital/ I-Shou University, Kaohsiung, Taiwan; 2School of Medicine, College of Medicine; 3Division of Nephrology, Department of Internal Medicine, E-DA Hospital/ I-Shou University, Kaohsiung, Taiwan; 4Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Chemistry, Chinese Culture University, Taipei, Taiwan; 6School of Medicine for International Students; 7Department of Laboratory Medicine; 8Division of Colorectal Surgery, Department of Surgery; 9Department of Neurosurgery; 10Department of Medical Education, E-DA Hospital/ I-Shou University, Kaohsiung, Taiwan; 11Division of Nephrology, Department of Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan; 12Department of Pediatrics, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Yi-Che LeeDivision of Nephrology, Department of Internal Medicine, E-DA Hospital/I-Shou University, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan, ROCTel +886-7-6150011 ext. 5121Email pipijer@gmail.com Yuan-Yow ChiouInstitute of Clinical Medicine, Department of Pediatrics, National Cheng Kung University Hospital, Medical College, No. 138, Sheng-Li Road, Tainan City 701, Taiwan, ROCTel +886-6-2353535 ext. 4184Fax +886-6-2753083Email yuanyow@mail.ncku.edu.twPurpose: Vitamin D is a novel potential therapeutic agent for peritoneal dialysis (PD)-related peritoneal fibrosis, but it can induce hypercalcemia and vascular calcification, which limits its applicability. In this study, we create nanotechnology-based drug delivery systems to investigate its therapeutics and side effects.Materials and methods: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino-(polyethylene glycol)2000] (DSPE-PEG) and L-α-phosphatidylcholine (PC), which packages with 1α,25(OH)2D3, were used to construct vitamin D nanoliposomes. To confirm the function and safety of vitamin D nanoliposomes, peritoneal mesothelial cells were treated with TGF-β1 and the reverse was attempted using vitamin D nanoliposomes. Antibodies (Ab) against the peritoneum-glycoprotein M6A (GPM6A) Ab were conjugated with vitamin D nanoliposomes. These particles were implanted into mice by intraperitoneal injection and the animals were monitored for the distribution and side effects induced by vitamin D.Results: Vitamin D nanoliposomes were taken up by the mesothelial cells over time without cell toxicity and it also provided the same therapeutic effect in vitro. In vivo study, fluorescent imaging showed vitamin D nanoliposomes allow specific peritoneum target effect and also ameliorate vitamin D side effect.Conclusion: Nanoliposomes vitamin D delivery systems for the prevention of PD-related peritoneal damage may be a potential clinical strategy in the future.Keywords: peritoneal dialysis, nanoliposome, vitamin D, fibrosis

Shu-Hui Lin,1,2,* Hsin-Kai Wang,3,4,* Kun-Tu Yeh,1,5 Hui-Chun Tai,1,6 Hui-Yi Wang,1 Lan-Ru Huang,2 Chun-Wen Chiu,7 Chia-Min Chung,8,9 Bharath Kumar Velmurugan101Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan; 2Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan; 3Public Health Bureau, Tainan City Government, Tainan, Taiwan; 4Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan; 5School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 6Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 7Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan; 8Graduate Institute of BioMedical Sciences, China Medical University, Taichung, Taiwan; 9Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan; 10Toxicology and Biomedicine Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam*These authors contributed equally to this work Purpose: c-MYC has been noted in many tumor types, but its functional significance and clinical utility in oral squamous cell carcinoma (OSCC) are not well known. Here we studied the expression of c-MYC in correlation to clinical outcome in patients with oral squamous cell carcinoma.Methods: The current study, using immunohistochemical staining, first examined c-MYC expression in OSCC patients and further correlated its expression with clinicopathological parameters.Results: c-MYC was expressed in the majority of OSCC patients (n=133). The c-MYC expression is associated with histological grade (P=0.0205) of patients with oral squamous cell carcinoma. Multivariate Cox regression analysis revealed that TN stage (P0.05). Multiplicative-scale interaction between T stage (III/IV) and low c-MYC expression on mortality risk was identified (P=0.0233). Kaplan–Meier survival analysis demonstrated that oral cancer patients (T III/IV stage) with high c-MYC expression had better survival than those with low and medium c-MYC expression (P=0.0270).Conclusion: Our data indicate that c-MYC is a potential biomarker that can be used as a therapeutic target for treating OSCC patients with T stage (III/IV).Keywords: T stage, c-MYC, OSCC, biomarker, survival

Bharath Kumar Velmurugan,1 Hsin-Kai Wang,2,3 Chia-Min Chung,4,5 Chien-Hsun Lee,6 Lan-Ru Huang,7 Kun-Tu Yeh,6,7* Shu-Hui Lin6,8*1Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam; 2Public Health Bureau, Tainan City Government, Tainan City, Taiwan; 3Jenteh Junior College of Medicine, Nursing and Management, Taiwan; 4Graduate Institute of BioMedical Sciences, China Medical University, Taichung, Taiwan; 5Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan; 6Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan; 7School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 8Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan *These authors contributed equally to this workIntroduction: Oral cancer is a prevalent form of cancer worldwide, particularly in Taiwan, and mechanisms involved in oral squamous cell carcinoma (OSCC) progression remain relatively unknown. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncoprotein, is aberrantly expressed in many human malignant tumors including oral cancer. However, the expression and role played by CIP2A in oral cancer pathogenesis remain obscure.Methods: In this study, immunohistochemistry was used to analyze CIP2A expression between OSCC tissues and their adjacent noncancerous tissues. Furthermore, associations between CIP2A expression and histopathological parameters were investigated.Results: In this study, we showed that CIP2A was overexpressed in most of the OSCC tissues. High CIP2A expression was significantly associated with moderate/poor tumor differentiation (P=0.02). No significant association was found between CIP2A expression and other clinical parameters. Kaplan–Meier analysis revealed that high CIP2A expression showed poorer survival rates than those with low CIP2A expression (P=0.047). Multivariate Cox regression analysis indicated that CIP2A expression, N stage, American Joint Committee on Cancer stage and clinical therapy were independent prognostic factors for survival.Conclusion: Thus, our study suggests that CIP2A is an independent prognostic marker for OSCC and a novel target for OSCC treatment.Keywords: CIP2A, OSCC: prognosis, survival, Taiwan

Cheng-Loong Liang,1 Hao-Kwan Wang,1 Fei-Kai Syu,2 Kuo-Wei Wang,1 Kang Lu,1 Po-Chou Liliang1 1Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan; 2Department of Pharmacy, China Medical University Hospital, Taichung City, Taiwan Purpose: Postvertebral augmentation vertebral compression fractures are common; repeated vertebral augmentation is usually performed for prompt pain relief. This study aimed to evaluate the incidence and risk factors of repeat vertebral augmentation.Methods: We performed a retrospective, nationwide, population-based longitudinal observation study, using the National Health Insurance Research Database (NHIRD) of Taiwan. All patients who received vertebral augmentation for vertebral compression fractures were evaluated. The collected data included patient characteristics (demographics, comorbidities, and medication exposure) and repeat vertebral augmentation. Kaplan–Meier and stratified Cox proportional hazard regressions were performed for analyses.Results: The overall incidence of repeat vertebral augmentation was 11.3% during the follow-up until 2010. Patients with the following characteristics were at greater risk for repeat vertebral augmentation: female sex (AOR=1.24; 95% confidence interval [CI]: 1.10–2.36), advanced age (AOR=1.60; 95% CI: 1.32–2.08), diabetes mellitus (AOR=4.31; 95% CI: 4.05–5.88), cerebrovascular disease (AOR=4.09; 95% CI: 3.44–5.76), dementia (AOR=1.97; 95% CI: 1.69–2.33), blindness or low vision (AOR=3.72; 95% CI: 2.32–3.95), hypertension (AOR=2.58; 95% CI: 2.35–3.47), and hyperlipidemia (AOR=2.09; 95% CI: 1.67–2.22). Patients taking calcium/ vitamin D (AOR=2.98; 95% CI: 1.83–3.93), bisphosphonates (AOR=2.11; 95% CI: 1.26–2.61), or calcitonin (AOR=4.59; 95% CI: 3.40–5.77) were less likely to undergo repeat vertebral augmentation; however, those taking steroids (AOR=7.28; 95% CI: 6.32–8.08), acetaminophen (AOR=3.54; 95% CI: 2.75–4.83), or nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR=6.14; 95% CI: 5.08–7.41) were more likely to undergo repeat vertebral augmentation.Conclusion: We conclude that the incidence of repeat vertebral augmentation is rather high. An understanding of risk factors predicting repeat vertebral augmentation provides valuable basis to improve health care for geriatric populations. Keywords: vertebroplasty, kyphoplasty, comorbidity, bisphosphonate, old ageTwo Letters to the Editor have been recieved and published İlhan et alWilson et al

Lu K, Liliang PC, Wang HK, Chen JS, Chen TY, Huang R, Chen HJ. J Pain Res. 2016;9:917–924. Page 917, author affiliation list, the authors have requested for the affiliations to be listed as shown below. Kang Lu1Po-Chou Liliang1Hao-Kuang Wang1Jui-Sheng Chen1Te-Yuan Chen1Ruyi Huang2Han-Jung Chen1,3 1Department of Neurosurgery, E-Da Hospital, I-Shou University, 2Department of Family Medicine, E-Da Hospital, I-Shou University, 3Department of Neurosurgery, E-Da Cancer Hospital, College of Medicine, I-Shou University, Kaohsiung, TaiwanRead the original article

Neck pain due to cervical facet joint pain has a prevalence of 36-60% in chronic neck pain. Pulsed radiofrequency for such pain has been verified. After proper patient selection, pulsed radiofrequency of the cervical facet joints provide long-term pain relief in a routine clinical setting. In the patient selection, clinical and sagittal alignment parameters are rarely discussed for the outcome. In the present study, we analyzed the factors from the clinical data and sagittal alignment parameters and investigated the associated predictors of pulsed radiofrequency for cervical facet joint pain. There were 204 patients with cervical facet joint pain who received a medial branch block and pulsed radiofrequency between 2015 and 2020 after excluding patients with neurological symptoms and other confounding factors. The patients were classified into good and poor outcome groups based on the improvement of the pain score(visual analog scale). Clinical and radiological data were analyzed. Multivariable logistic model showed that the predictors were cervical lordosis including two methods (odds ratio [OR] 0.92, 95% confidence interval [CI]: 0.89-0.96 for C2-C7 Cobb angle; OR 0.91, 95% CI: 0.88-0.95 for the angle measured by the Jackson method), ossification of the nuchal ligament, number of diseased facet joints, anterior cervical discectomy with fusion, and adjacent facet joint after anterior cervical discectomy with fusion. With the results, we demonstrated that the outcome were related to cervical lordosis including two methods, formation of ossification of nuchal ligament, the number of diseased facet joints, post anterior cervical discectomy with fusion, and adjacent facet joint post anterior cervical discectomy with fusion. The corresponding optimal cutoff for discriminating a poor outcome was 7° for the C2-C7 Cobb angle and - 2° for the angle measured using the Jackson method., Competing Interests: Declarations Ethics approval The study was approved by the Institutional Review Board of E-Da hospital (EMRP-111-065). Competing interests The authors declare no competing interests. Medical writing, editorial, and other assistance No., (© 2024. The Author(s).)

Time-resolved x-ray crystallography (TR-X) at synchrotrons and free electron lasers is a promising technique for recording dynamics of molecules at atomic resolution. While experimental methods for TR-X have proliferated and matured, data analysis is often difficult. Extracting small, time-dependent changes in signal is frequently a bottleneck for practitioners. Recent work demonstrated this challenge can be addressed when merging redundant observations by a statistical technique known as variational inference (VI). However, the variational approach to time-resolved data analysis requires identification of successful hyperparameters in order to optimally extract signal. In this case study, we present a successful application of VI to time-resolved changes in an enzyme, DJ-1, upon mixing with a substrate molecule, methylglyoxal. We present a strategy to extract high signal-to-noise changes in electron density from these data. Furthermore, we conduct an ablation study, in which we systematically remove one hyperparameter at a time to demonstrate the impact of each hyperparameter choice on the success of our model. We expect this case study will serve as a practical example for how others may deploy VI in order to analyze their time-resolved diffraction data., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Among human milk oligosaccharides (HMOs), linear HMOs are synthesized through mature but varied routes. Although branched HMOs can be synthesized by chemical, enzymatic, or chemoenzymatic methods, these methods cannot be easily applied to the synthesis of asymmetric multiantennary oligosaccharides. Herein, we developed a controllable method to synthesize asymmetric biantennary HMOs. In our synthetic route, GlcNAcβ1,3(GlcN3β1,6)Glaβ1,4Glc was first chemically synthesized as the core tetrasaccharide, which contains β1,6GlcN3 as the "stop" sugar in transferase-catalyzed glycosylation. The desired sugars at the GlcNAcβ1-3Gal arm can be assembled using galactosyltransferase, N -acetylglucosaminyltransferase, and fucosyltransferase. Then, the Staudinger reduction and acetylation were used to transform GlcN3 to GlcNAc and assemble sugars by initiating the "go" process. By manipulating transferase-catalyzed glycosylations, 22 natural asymmetric biantennary oligosaccharides were synthesized., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Competing Interests: The authors declare no conflicts of interest.

Most x-ray sources are inherently polychromatic. Polychromatic ("pink") x-rays provide an efficient way to conduct diffraction experiments as many more photons can be used and large regions of reciprocal space can be probed without sample rotation during exposure-ideal conditions for time-resolved applications. Analysis of such data is complicated, however, causing most x-ray facilities to discard >99% of x-ray photons to obtain monochromatic data. Key challenges in analyzing polychromatic diffraction data include lattice searching, indexing and wavelength assignment, correction of measured intensities for wavelength-dependent effects, and deconvolution of harmonics. We recently described an algorithm, Careless, that can perform harmonic deconvolution and correct measured intensities for variation in wavelength when presented with integrated diffraction intensities and assigned wavelengths. Here, we present Laue-DIALS, an open-source software pipeline that indexes and integrates polychromatic diffraction data. Laue-DIALS is based on the dxtbx toolbox, which supports the DIALS software commonly used to process monochromatic data. As such, Laue-DIALS provides many of the same advantages: an open-source, modular, and extensible architecture, providing a robust basis for future development. We present benchmark results showing that Laue-DIALS, together with Careless, provides a suitable approach to the analysis of polychromatic diffraction data, including for time-resolved applications., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA-seq analysis, it is found high expression of the splicing factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping of interleukin-18 (IL-18), resulting in the expression of ΔIL-18, an isoform specifically expressed in tumors. That ΔIL-18 promotes GBC immune escape by down-regulating FBXO38 transcription levels in CD8+T cells to reduce PD-1 ubiquitin-mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL-18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL-18 production displayed anti-tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL-18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL-18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL-18 pre-mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Due to the specific loads that occur in combat sports athletes' forearm muscles, we decided to compare the immediate effect of monotherapy with the use of compressive heat (HT), cold (CT), and alternating therapy (HCT) in terms of eliminating muscle tension, improving muscle elasticity and tissue perfusion and forearm muscle strength. This is a single-blind, randomized, experimental clinical trial. Group allocation was performed using simple 1:1 sequence randomization using the website randomizer.org. The study involved 40 40 combat sports athletes divided into four groups and four therapeutic sessions lasting 20 min. (1) Heat compression therapy session (HT, n = 10) (2) (CT, n = 10), (3) alternating (HCT, n = 10), and sham, control (ShT, n = 10). All participants had measurements of tissue perfusion (PU, [non-reference units]), muscle tension (T-[Hz]), elasticity (E-[arb- relative arbitrary unit]), and maximum isometric force (Fmax [kgf]) of the dominant hand at rest (Rest) after the muscle fatigue protocol (PostFat.5 min), after therapy (PostTh.5 min) and 24 h after therapy (PostTh.24 h). A two-way ANOVA with repeated measures: Group (ColdT, HeatT, ContrstT, ControlT) × Time (Rest, PostFat.5 min, PostTh.5 min, Post.24 h) was used to examine the changes in examined variables. Post-hoc tests with Bonferroni correction and ± 95% confidence intervals (CI) for absolute differences (△) were used to analyze the pairwise comparisons when a significant main effect or interaction was found. The ANOVA for PU, T, E, and Fmax revealed statistically significant interactions of Group by Time factors (p < 0.0001), as well as main effects for the Group factors (p < 0.0001; except for Fmax). In the PostTh.5 min. Period, significantly (p < 0.001) higher PU values were recorded in the HT (19.45 ± 0.91) and HCT (18.71 ± 0.67) groups compared to the ShT (9.79 ± 0.35) group (△ = 9.66 [8.75; 10.57 CI] > MDC (0.73) , and △ = 8.92 [8.01; 9.83 CI] > MDC (0.73) , respectively). Also, significantly (p < 0.001) lower values were recorded in the CT (3.69 ± 0.93) compared to the ShT (9.79 ± 0.35) group △ = 6.1 [5.19; 7.01 CI] > MDC (0.73) . For muscle tone in the PostTh.5 m period significantly (p < 0.001) higher values were observed in the CT (20.08 ± 0.19 Hz) group compared to the HT (18.61 ± 0.21 Hz), HCT (18.95 ± 0.41 Hz) and ShT (19.28 ± 0.33 Hz) groups (respectively: △ = 1.47 [1.11; 1.83 CI] > MDC (0.845) ; △ = 1.13 [0.77; 1.49 CI] > MDC (0.845) , and △ = 0.8 [0.44; 1.16 CI], < MDC (0.845) ). The highest elasticity value in the PostTh.5 m period were observed in the CT (1.14 ± 0.07) group, and it was significantly higher than the values observed in the HT (0.97 ± 0.03, △ = 0.18 [0.11; 0.24 CI] > MDC (0.094) , p < 0.001), HCT (0.90 ± 0.04, △ = 0.24 [0.17; 0.31 CI] > MDC (0.094) , p < 0.001) and ShT (1.05 ± 0.07, △ = 0.094 [0.03; 0.16 CI] = MDC (0.094) , p = 0.003) groups. For Fmax, there were no statistically significant differences between groups at any level of measurement. The results of the influence of the forearm of all three therapy forms on the muscles' biomechanical parameters confirmed their effectiveness. However, the effect size of alternating contrast therapy cannot be confirmed, especially in the PostTh24h period. Statistically significant changes were observed in favor of this therapy in PU and E measurements immediately after therapy (PostTh.5 min). Further research on contrast therapy is necessary., (© 2024. The Author(s).)

The voltage-dependent anion channel (VDAC) is a crucial mitochondrial protein that facilitates ion and metabolite exchange between mitochondria and the cytosol. Initially characterized over three decades ago, the structure of VDAC-1 was resolved in 2008, revealing a novel β-barrel protein architecture. This study presents the first room-temperature crystal structure of mouse VDAC-1 (mVDAC-1), which is a significant step toward understanding the channel's gating mechanism. The new structure, obtained at a 3.3 Å resolution, demonstrates notable differences from the previously determined cryogenic structure, particularly in the loop regions, which may be critical for the transition between the 'open' and 'closed' states of VDAC-1. Comparative analysis of the root-mean-square deviation (R.M.S.D.) and B-factors between the cryogenic and room-temperature structures suggests that these conformational differences, although subtle, are important for VDAC's functional transitions. The application of electric field-stimulated X-ray crystallography (EF-X) is proposed as a future direction to resolve the 'closed' state of VDAC-1 by inducing voltage-driven conformational changes in order to elucidate the dynamic gating mechanism of VDAC-1. Our findings have profound implications for understanding the molecular basis of VDAC's role in mitochondrial function and its regulation under physiological conditions.

The current standard method for amino acid signal identification in protein NMR spectra is sequential assignment using triple-resonance experiments. Good software and elaborate heuristics exist, but the process remains laboriously manual. Machine learning does help, but its training databases need millions of samples that cover all relevant physics and every kind of instrumental artifact. In this communication, we offer a solution to this problem. We propose polyadic decompositions to store millions of simulated three-dimensional NMR spectra, on-the-fly generation of artifacts during training, a probabilistic way to incorporate prior and posterior information, and integration with the industry standard CcpNmr software framework. The resulting neural nets take [ 1 H, 13 C] slices of mixed pyruvate-labeled HNCA spectra (different CA signal shapes for different residue types) and return an amino acid probability table. In combination with primary sequence information, backbones of common proteins (GB1, MBP, and INMT) are rapidly assigned from just the HNCA spectrum.

Time-resolved X-ray crystallography (TR-X) at synchrotrons and free electron lasers is a promising technique for recording dynamics of molecules at atomic resolution. While experimental methods for TR-X have proliferated and matured, data analysis is often difficult. Extracting small, time-dependent changes in signal is frequently a bottleneck for practitioners. Recent work demonstrated this challenge can be addressed when merging redundant observations by a statistical technique known as variational inference (VI). However, the variational approach to time-resolved data analysis requires identification of successful hyperparameters in order to optimally extract signal. In this case study, we present a successful application of VI to time-resolved changes in an enzyme, DJ-1, upon mixing with a substrate molecule, methylglyoxal. We present a strategy to extract high signal-to-noise changes in electron density from these data. Furthermore, we conduct an ablation study, in which we systematically remove one hyperparameter at a time to demonstrate the impact of each hyperparameter choice on the success of our model. We expect this case study will serve as a practical example for how others may deploy VI in order to analyze their time-resolved diffraction data.

Chemical and conformational changes underlie the functional cycles of proteins. Comparative crystallography can reveal these changes over time, over ligands, and over chemical and physical perturbations in atomic detail. A key difficulty, however, is that the resulting observations must be placed on the same scale by correcting for experimental factors. We recently introduced a Bayesian framework for correcting (scaling) X-ray diffraction data by combining deep learning with statistical priors informed by crystallographic theory. To scale comparative crystallography data, we here combine this framework with a multivariate statistical theory of comparative crystallography. By doing so, we find strong improvements in the detection of protein dynamics, element-specific anomalous signal, and the binding of drug fragments.

Two cases of complicated pain exist: posterior screw fixation and myofascial pain. Intramuscular pulsed radiofrequency (PRF) may be an alternative treatment for such patients. This is a two-stage animal study. In the first stage, two muscle groups and two nerve groups were subdivided into a high-temperature group with PRF at 58 °C and a regular temperature with PRF at 42 °C in rats. In the second stage, two nerve injury groups were subdivided into nerve injury with PRF 42 °C on the sciatic nerve and muscle. Blood and spinal cord samples were collected. In the first stage, the immunohistochemical analysis showed that PRF upregulated brain-derived neurotrophic factor (BDNF) in the spinal cord in both groups of rats. In the second stage, the immunohistochemical analysis showed significant BDNF and tropomyosin receptor kinase B (TrkB) expression within the spinal cord after PRF in muscles and nerves after nerve injury. The blood biomarkers showed a significant increase in BDNF levels. PRF in the muscle in rats could upregulate BDNF-TrkB in the spinal cord, similar to PRF on the sciatica nerve for pain relief in rats. PRF could be considered clinically for patients with complicated pain and this study also demonstrated the role of BDNF in pain modulation. The optimal temperature for PRF was 42 °C.

Introduction: Most adrenal tumors are benign and primary adrenal malignancies are relatively rare. Primary adrenal lymphoma (PAL) is a very rare and highly aggressive malignant tumor with unknown etiology, atypical clinical symptoms, nonspecific imaging manifestations, difficult disease diagnosis and poor prognosis., Case Report: This case report details a 42-year-old woman who was admitted to the hospital with a 1-year-old bilateral adrenal mass and 1-month-old left upper abdominal pain. Enhanced CT of the abdomen showed a right adrenal nodule and a large occupying lesion in the left adrenal region, with a high probability of pheochromocytoma. Intraoperatively, a huge tumor measuring about 12*12*10 cm was found in the left adrenal region, infiltrating the left kidney, spleen and pancreatic tail. Postoperative pathology: lymphocytes were found in the renal capsule and subcapsule, lymphocytes were found in the pancreas; lymphocytes were found in the spleen. Consider a tumor of the lymphohematopoietic system, possibly lymphoma., Conclusion: This case demonstrates that primary adrenal diffuse large B-cell lymphoma (PADLBCL) is highly aggressive, has a poor prognosis, is prone to recurrence, has poor therapeutic outcomes, and is difficult to diagnose. Clinicians should consider the possibility of PADLBCL when encountering huge adrenal-occupying lesions and consider chemotherapy before surgery. Reducing the tumor size before surgery is a more favorable therapeutic approach, thus prolonging the patient life and improving the quality of survival., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria., Case Presentation: We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone., Conclusions: Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren't enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome., (© 2024. The Author(s).)

Background: With the development of messenger RNA (mRNA)-based therapeutics for malignant tumor, mRNA vaccines have shown considerable promise for tumor immunotherapy. Immunophenotypes can reflect the tumor microenvironment, which might have a significant influence on the effect of immunotherapy. This study seeks to discover and validate effective antigens that can be employed to develop mRNA vaccines for hepatocellular carcinoma (HCC) and to construct immunophenotypes and immune landscapes to identify potential beneficiaries., Methods: RNA sequencing (RNASeq) data, mutation information, and clinical information were obtained from HCC patients and control cases from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium - Liver Cancer (ICGC-LIRI) and Gene Expression Omnibus (GEO) cohorts. Gene Expression Profiling Interactive Analysis (GEPIA2.0), cBioPortal for Cancer Genomics (cBioPortal), Tumor IMmune Estimation Resource (TIMER2.0), and immunohistochemistry (IHC) were employed to discover tumor antigens. ConsensusClusterPlus was employed to perform consistency matrix building and immunophenotypic clustering. Single sample gene set enrichment analysis (ssGSEA), ESTIMATE and monocle2 were employed to map immune cell distribution. Weighted correlation network analysis (WGCNA) was employed to identify potential gene modules that influence the efficacy of mRNA vaccines., Results: Six antigen targets were discovered in the TCGA cohort, including AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 , which were associated with antigen-presenting cell infiltration and poor prognosis. IHC scores of AURKA, CDC25C and MCM3 were higher in tumor tissues, and high scores of AURKA and CDC25C indicated poor prognosis in the validation cohort. Five immunophenotypes derived from TCGA-LIHC and ICGC-LIRI cohorts were consistent. Furthermore, increased expression of blue and black modules may reduce vaccine responsiveness., Conclusions: AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 may be potential targets for mRNA vaccine development for HCC, especially AURKA and CDC25C . HCC patients with IS1 and IS5 subtypes perhaps present an autoimmunosuppressed state, then IS2 and IS3 subtypes perhaps the potential beneficiaries., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1237/coif) and report that the fund supported the experimental parts (reagent purchase, experimental materials, etc.) involved in this manuscript was Basic and Applied Basic Research Foundation of Guangdong Province (Grant No. 2020A1515011379 to He-Yun Zhang). The authors have no other conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus . Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health., Competing Interests: The authors have declared no competing interests., (© 2024 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Background: Activating signal cointegrator 3 (ASCC3) has been identified as an oncogenic factor that impairs host immune defense. However, the underlying mechanisms of carcinogenesis and its impact on the antitumor immune response remain unclear. In this study, we aimed to investigate the molecular mechanisms of ASCC3 in the progression of non-small cell lung cancer (NSCLC)., Methods: Single-cell sequencing data from the Gene Expression Omnibus and gene expression profiles from The Cancer Genome Atlas database were analyzed. The expression, clinical relevance and biological functions of ASCC3 in NSCLC were explored. Then, RNA sequencing, immunoprecipitation, mass spectrometry, immunofluorescence, and flow cytometry analyses were conducted to explore the underlying molecular mechanisms. In addition, in vivo experiments in mouse models were conducted to explore the probability of ASCC3 knockdown to improve the efficacy of anti-Programmed Death-1 (PD-1) therapy in NSCLC., Results: ASCC3 was significantly upregulated in NSCLC and correlated with poor pathological characteristics and prognosis in patients with NSCLC. Overexpression of ASCC3 promoted malignant phenotypes of NSCLC cells and induced an immunosuppressive tumor microenvironment, which was characterized by a decrease in CD8 + T cells, natural killer cells and dendritic cells but an increase in regulatory T(Treg) cells. Mechanistically, ASCC3 stabilized signal transducer and activator of transcription (STAT)3 signaling by recruiting Cullin-associated and neddylation dissociated 1 (CAND1), which inhibited ubiquitin-mediated degradation of STAT3, thereby impairing the type I interferon response of tumor cells and promoting the immunosuppression and progression of NSCLC. Furthermore, high expression of ASCC3 impaired the efficacy of anti-PD-1 therapy, and an anti-PD-1 antibody combined with ASCC3 knockdown exerted promising synergistic efficacy in a preclinical mouse model., Conclusion: ASCC3 could stabilize the STAT3 pathway via CAND1, reshaping the tumor microenvironment and inducing resistance to anti-PD-1 therapy, which promotes the progression of NSCLC. It is a reliable prognostic indicator and can be a target in combination therapy for NSCLC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Long noncoding RNAs (lncRNAs) are a distinct subtype of RNA that lack protein-coding capacity but exert significant influence on various cellular processes. In non-small cell lung cancer (NSCLC), dysregulated lncRNAs act as either oncogenes or tumor suppressors, contributing to tumorigenesis and tumor progression. LncRNAs directly modulate gene expression, act as competitive endogenous RNAs by interacting with microRNAs or proteins, and associate with RNA binding proteins. Moreover, lncRNAs can reshape the tumor immune microenvironment and influence cellular metabolism, cancer cell stemness, and angiogenesis by engaging various signaling pathways. Notably, lncRNAs have shown great potential as diagnostic or prognostic biomarkers in liquid biopsies and therapeutic strategies for NSCLC. This comprehensive review elucidates the significant roles and diverse mechanisms of lncRNAs in NSCLC. Furthermore, we provide insights into the clinical relevance, current research progress, limitations, innovative research approaches, and future perspectives for targeting lncRNAs in NSCLC. By summarizing the existing knowledge and advancements, we aim to enhance the understanding of the pivotal roles played by lncRNAs in NSCLC and stimulate further research in this field. Ultimately, unraveling the complex network of lncRNA-mediated regulatory mechanisms in NSCLC could potentially lead to the development of novel diagnostic tools and therapeutic strategies., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

There is no strong evidence indicating the optimal treatment for breast cancer (BC) and no specific prognostic model. The aim of this study was to establish nomograms to predict the overall survival (OS) of BC patients receiving chemoradiotherapy and surgery, thereby quantifying survival benefits and improving patient management. A total of 1877 patients with primary nonmetastatic BC who received chemoradiotherapy and surgery from 2010 to 2019 were identified from the Surveillance, Epidemiology and End Results (SEER) database as the training cohort, 804 as the internal validation cohort, and 796 patients from the First Affiliated Hospital of Zhengzhou University (n=324) and Jiaxing Maternal and Child Health Hospital (n=472) as the external validation cohort. Least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analyses were performed in the training cohort to determine independent prognostic factors for BC, and a nomogram was constructed to predict 3-year, 5-year, and 8-year OS. The final model incorporated 7 factors that significantly affect OS: race, location, positive regional nodes, T stage, N stage, subtype, and grade. The calibration curves showed good consistency between the predicted survival and actual outcomes. Time-dependent receiver operating characteristic (ROC) curves and the time-dependent area under the curve (AUC) confirmed that the accuracy and clinical usefulness of the constructed nomograms were favorable. Decision curve analysis (DCA) and net reclassification improvement (NRI) also demonstrated that this nomogram was more suitable for clinical use than the 7 th American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system and the previous prediction model. In the training cohort and the internal validation cohort, the concordance indices (C-index) of the nomogram for predicting OS (0.723 and 0.649, respectively) were greater than those of the 7 th AJCC TNM staging system and the previous prediction model. In addition, based on Kaplan-Meier (K-M) survival curves, the survival differences among different risk stratifications were statistically significant, indicating that our risk model was accurate. In this study, we determined independent prognostic factors for OS in patients with primary nonmetastatic BC treated with chemoradiotherapy and surgery. A new and accurate nomogram for predicting 3-, 5-, and 8-year OS in this patient population was developed and validated for potential clinical applicability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (AJCR Copyright © 2023.)

Evidence indicates that patients with chronic low back pain (CLBP) have lumbar multifidus muscle (LM) activation deficit which might be caused by changes in cortical excitability. Anodal transcranial direct current stimulation (a-tDCS) can be used to restore cortical excitability. This study aimed to (1) determine the immediate effects of a-tDCS on the cortical excitability and LM activation and (2) explore the relationship between cortical excitability and LM activation. Thirteen participants with CLBP during remission and 11 healthy participants were recruited. Cortical excitability (peak-to-peak motor evoked potential amplitude; P2P and cortical silent period; CSP) and LM activation were measured at pre- and post-intervention. We found significant difference (P < 0.05) in P2P between groups. However, no significant differences (P > 0.05) in P2P, CSP and LM activation were found between pre- and post-intervention in CLBP. The CLBP group demonstrated significant correlation (P = 0.05) between P2P and LM activation. Although our finding demonstrates change in P2P in the CLBP group, one-session of a-tDCS cannot induce changes in cortical excitability and LM activation. However, moderate to strong correlation between P2P and LM activation suggests the involvement of cortical level in LM activation deficit. Therefore, non-significant changes could have been due to inadequate dose of a-tDCS., (© 2023. Springer Nature Limited.)

Purpose: The purpose of this study was to investigate the in vivo morphologic features of the cornea in patients with unilateral posterior interstitial keratitis., Methods: Seven eyes of 7 patients with unilateral posterior interstitial keratitis were examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). The imaging features of the cornea were evaluated and analyzed., Results: By slit-lamp examination, the posterior corneal stromal opacities were observed in all 7 eyes, and deep neovascularization in 4 eyes. The posterior stromal opacities showed higher reflectivity with an intact overlying epithelium by AS-OCT and did not invade the Bowman's layer in all cases. IVCM revealed highly reflective dispersed microdots, needle-shaped bodies, and increased reflectivity of keratocytes in the lesion site in all patients. Active Langerhans cells and an attenuated subbasal nerve plexus were observed in 5 eyes. After treatment, the active Langerhans cells disappeared; however, highly reflective microdots and needle-shaped bodies remained., Conclusion: The three-dimensional evaluation of slit-lamp biomicroscopy, AS-OCT, and IVCM may help in the early diagnosis of patients with posterior interstitial keratitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gu, Gao, Wang, He, Peng, Xiao and Hong.)

Few studies have discussed the disease nature and treatment outcomes for bilateral cavernous sinus dural arteriovenous fistula (CSDAVF). This study aimed to investigate the clinical features and treatment outcomes of bilateral CSDAVF. Embase, Medline, and Cochrane library were searched for studies that specified the outcomes of bilateral CSDAVF from inception to April 2022. The classification, clinical presentation, angiographic feature, surgical approach, and treatment outcomes were collected. Meta-analysis was performed using the random effects model. Eight studies reporting 97 patients were included. The clinical presentation was mainly orbital (n = 80), cavernous (n = 52) and cerebral (n = 5) symptoms. The most approached surgical route was inferior petrosal sinus (n = 80), followed by superior orbital vein (n = 10), and alternative approach (n = 7). Clinical symptoms of 88% of the patients (95% CI 80-93%, I 2  = 0%) were cured, and 82% (95% CI 70-90%, I 2  = 7%) had angiographic complete obliteration of fistulas during follow up. The overall complication rate was 18% (95% CI 11-27%, I 2  = 0%). Therefore, endovascular treatment is an effective treatment for bilateral CSDAVF regarding clinical or angiographic outcomes. However, detailed evaluation of preoperative images and comprehensive surgical planning of the approach route are mandatory owing to complexity of the lesions., (© 2023. The Author(s).)

Background: The scavenger receptor CD36 was reported to be highly expressed on tumor-infiltrating CD8 + T cells, but the clinical role remains obscure. This study aims to explore the infiltration and clinical value of CD36 + CD8 + T cells in NSCLC., Methods: Immunohistochemistry and immunofluorescence were conducted for survival analyses and immunological evaluation in 232 NSCLC patients in Zhongshan Hospital. Flow cytometry analyses were carried out to assess the immune cells from fresh tumor samples, non-tumor tissues and peripheral blood. In vitro tumor infiltrating lymphocytes cultures were conducted to test the effect of CD36 blockage., Results: Accumulation of CD36 + CD8 + T cells in tumor tissues was correlated with more advanced stage (p < 0.001), larger tumor size (p < 0.01), and lymph node metastasis (p < 0.0001) in NSCLC. Moreover, high infiltration of CD36 + CD8 + T cells indicated poor prognosis in terms of both overall survival (OS) and recurrence-free survival (RFS) and inferior chemotherapy response. CD36 + CD8 + T cells showed decreased GZMB (p < 0.0001) and IFN-γ (p < 0.001) with elevated PD-1 (p < 0.0001) and TIGIT (p < 0.0001). Analysis of tumor-infiltrating immune cell landscape revealed a positive correlation between CD36 + CD8 + T cells and Tregs (p < 0.01) and M2-polarized macrophages (p < 0.01) but a negative correlation with Th1 (p < 0.05). Notably, inhibition of CD36 partially restored the cytotoxic function of CD8 + T cells by producing more GZMB and IFN-γ., Conclusion: CD36 + CD8 + T cells exhibit impaired immune function and high infiltration of CD36 + CD8 + T cells indicated poor prognosis and inferior chemotherapy response in NSCLC patients. CD36 could be a therapeutic target in combination with chemotherapy in NSCLC patients., (© 2023. The Author(s).)

Immunotherapy has emerged to play a rapidly expanding role in the treatment of cancers. Currently, many clinical trials of therapeutic agents are on ongoing with majority of immune checkpoint inhibitors (ICIs) especially programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1, two main immune checkpoints, are expressed at high levels in thymic epithelial tumors (TETs) and could be predictors of the progression and immunotherapeutic efficacy of TETs. However, despite inspiring efficacy reported in clinical trials and clinical practice, significantly higher incidence of immune-related adverse events (irAEs) than other tumors bring challenges to the administration of ICIs in TETs. To develop safe and effective immunotherapeutic patterns in TETs, understanding the clinical properties of patients, the cellular and molecular mechanisms of immunotherapy and irAEs occurrence are crucial. In this review, the progress of both basic and clinical research on immune checkpoints in TETs, the evidence of therapeutic efficacy and irAEs based on PD-1 /PD-L1 inhibitors in TETs treatment are discussed. Additionally, we highlighted the possible mechanisms underlying irAEs, prevention and management strategies, the insufficiency of current research and some worthy research insights. High PD-1/PD-L1 expression in TETs provides a rationale for ICI use. Completed clinical trials have shown an encouraging efficacy of ICIs, despite the high rate of irAEs. A deeper mechanism understanding at molecular level how ICIs function in TETs and why irAEs occur will help maximize the immunotherapeutic efficacy while minimizing irAEs risks in TET treatment to improve patient prognosis., (© 2023. The Author(s).)

Background: To explore the effects of Ving Tsun (VT) sticking-hand training on knee joint proprioception and leg muscular performance among community-dwelling middle-aged and older adults., Methods: Thirty-three middle-aged and older adults were randomly assigned to either the VT or control group. The VT group received sticking-hand training twice/week for 3 months. Data were collected before and after the intervention period. The primary outcome was knee joint repositioning error, which was measured using knee joint active repositioning tests. The secondary outcomes included the maximum muscle strength and time to maximum muscle strength of the major leg muscles., Results: No significant group, time, or group-by-time interaction effects were found for the knee joint repositioning error (p > 0.05). The maximum muscle strength of the knee flexors increased over time in the VT group only (p = 0.038). In addition, the time to maximum muscle strength in the hip extensors and flexors increased over time in both groups (p < 0.05). For the knee extensors and flexors, the time to maximum muscle strength increased in the control (p = 0.027) and VT (p = 0.019) groups, respectively, over time., Conclusions: VT sticking-hand training could improve the maximum muscle strength of the knee flexors but could not attenuate the age-related deterioration in leg muscle contraction speed nor improve knee joint proprioception among community-dwelling middle-aged and older adults., Trial Registration: ClinicalTrials.gov NCT03318289. Registered on 23 October 2017., (© 2023. The Author(s).)

Patients with end-stage renal disease (ESRD) are at a higher mortality risk compared with the general population. Previous studies have described a relationship between mortality and patients with ESRD, but the data on standardized mortality ratio (SMR) corresponding to different causes of death in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) are limited. This study was designed as a nationwide population-based retrospective cohort study. Incident dialysis patients between January 2000 and December 2015 in Taiwan were included. Using data acquired from the Taiwan Death Registry, SMR values were calculated and compared with the overall survival. The results showed there were a total of 128,966 patients enrolled, including 117,376 incident HD patients and 11,590 incident PD patients. It was found that 75,297 patients (58.4%) died during the period of 2000-2017. The overall SMR was 5.21. The neoplasms SMR was 2.11; the endocrine, nutritional, metabolic, and immunity disorders SMR was 13.53; the circulatory system SMR was 4.31; the respiratory system SMR was 2.59; the digestive system SMR was 6.1; and the genitourinary system SMR was 27.22. Therefore, more attention should be paid to these diseases in clinical care.

Background: Multiple perioperative inflammatory markers are considered important factors affecting the long-term survival of esophageal cancer (EC) patients. Hematological parameters, whether single or combined, have high predictive value., Aim: To investigate the inflammatory status of patients with preoperative EC using blood inflammatory markers, and to establish and validate competing risk nomogram prediction models for overall survival (OS) and progression-free survival (PFS) in EC patients., Methods: A total of 508 EC patients who received radical surgery (RS) treatment in The First Affiliated Hospital of Zhengzhou University from August 5, 2013, to May 1, 2019, were enrolled and randomly divided into a training cohort (356 cases) and a validation cohort (152 cases). We performed least absolute shrinkage and selection operator (LASSO)-univariate Cox- multivariate Cox regression analyses to establish nomogram models. The index of concordance (C-index), time-dependent receiver operating characteristic (ROC) curves, time-dependent area under curve (AUC) and calibration curves were used to evaluate the discrimination and calibration of the nomograms, and decision curve analysis (DCA) was used to evaluate the net benefit of the nomograms. The relative integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to evaluate the improvement in predictive accuracy of our new model compared with the AJCC staging system and another traditional model. Finally, the relationship between systemic inflammatory response markers and prognostic survival was explored according to risk plot, time-dependent AUC, Kaplan-Meier and restricted cubic spline (RCS)., Results: Based on the multivariate analysis for overall survival (OS) in the training cohort, nomograms with 10 variables, including the aggregate index of systemic inflammation (AISI) and lymphocyte-to-monocyte ratio (LMR), were established. Time-dependent ROC, time-dependent AUC, calibration curves, and DCA showed that the 1-, 3-, and 5 year OS and PFS probabilities predicted by the nomograms were consistent with the actual observations. The C-index, NRI, and IDI of the nomograms showed better performance than the AJCC staging system and another prediction model. Moreover, risk plot, time-dependent AUC, and Kaplan-Meier showed that higher AISI scores and lower LMR were associated with poorer prognosis, and there was a nonlinear relationship between them and survival risk., Conclusion: AISI and LMR are easy to obtain, reproducible and minimally invasive prognostic tools that can be used as markers to guide the clinical treatment and prognosis of patients with EC., (© 2023. The Author(s).)

Objective: Ultrasound shear wave elastography is an objective tool to evaluate the stiffness of human tissues. Patients with sialolithiasis could be treated by interventional sialendoscopy with a high success rate. Sialolithiasis could be extracted, and the diseased gland could be preserved and evaluated after treatment. Whether ultrasound shear wave elastography could be used for objective outcome measurement and short-term follow-up of the parenchyma of gland in patients with sialolithiasis remains unclear., Methods: This retrospective self-controlled study was conducted. Patients with sialolithiasis treated by interventional sialendoscopy and followed by high-resolution ultrasound shear wave elastography were selected between January and September 2017., Results: Seventeen patients with sialolithiasis (mean age: 39.63 ± 12.49 years), including 10 women and 7 men, were enrolled. Fifteen patients had sialolithiasis in the submandibular gland and two in the parotid gland. The preoperative value of shear wave velocity was significantly higher in the diseased gland than in the contralateral normal gland ( p  < .001; 95% confidence interval [CI], 0.3915-0.6046). After successful treatment by interventional sialendoscopy surgery, the shear wave velocity of the diseased gland decreased significantly ( p  = 0.001; 95% CI, -0.38792 to -0.20474). However, there was a significant difference between the diseased and contralateral normal glands ( p  = 0.001; 95% CI, 0.0423-0.2895) after 1.55 months of surgery., Conclusion: Ultrasound shear wave elastography could be an adjuvant tool to distinguish sialolithiasis-affected diseased glands from contralateral normal glands and assess the short-term treatment outcome objectively. The changing trend of shear wave velocity could help monitor the healing process of the parenchyma in the diseased gland after treatment., Level of Evidence: 4., Competing Interests: The authors declare no funding, financial relationships, or conflicts of interest related to the subject matter or materials discussed in this article., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Gut dysbiosis has been reported in chronic hepatitis B (CHB) infection, however its role in CHB progression and antiviral treatment remains to be clarified. Herein, the present study aimed to characterize gut microbiota (GM) in patients with chronic hepatitis B virus infection-associated liver diseases (HBV-CLD) by combining microbiome with metabolome analyses and to evaluate their effects on peripheral immunity. Fecal samples from HBV-CLD patients (n = 64) and healthy controls (n = 17) were collected for 16s rRNA sequencing. Fecal metabolomics was measured with untargeted liquid chromatography-mass spectrometry in subgroups of 58 subjects. Lineage changes of peripheral blood mononuclear cells (PBMCs) were determined upon exposure to bacterial extracts (BE) from HBV-CLD patients. Integrated analyses of microbiome with metabolome revealed a remarkable shift of gut microbiota and metabolites in HBV-CLD patients, and disease progression and antiviral treatment were found to be two main contributing factors for the shift. Concordant decreases in Turicibacter with 4-hydroxyretinoic acid were detected to be inversely correlated with serum AST levels through host-microbiota-metabolite interaction analysis in cirrhotic patients. Moreover, depletion of E.hallii group with elevated choline was restored in patients with 5-year antiviral treatment. PBMC exposure to BE from non-cirrhotic patients enhanced expansion of T helper 17 cells; however, BE from cirrhotics attenuated T helper 1 cell count. CHB progression and antiviral treatment are two main factors contributing to the compositional shift in microbiome and metabolome of HBV-CLD patients. Peripheral immunity might be an intermediate link in gut microbe-host interplay underlying CHB pathogenesis.

Rationale: Amyloidosis is a group of benign lesions characterized by extracellular deposition of amyloid proteins. Amyloidosis lesions can occur in various organs of the body, but rarely in the urinary system. Amyloidosis in the bladder trigone is extremely rare., Patient Concerns: An 80-year-old female patient presented with painless whole-course gross hematuria with reddish urine and no blood clots, accompanied by right lumbar discomfort., Diagnosis: Based on the patient's medical history and cystoscopy findings, the relevant literature was reviewed and a preoperative diagnosis of bladder tumor was made, although bladder amyloidosis was not excluded. Postoperative pathology ultimately revealed bladder amyloidosis., Interventions: The patient underwent resection of bladder tumor and ureteral stent implantation. Postoperatively, the patient was maintained on antibiotics and oral colchicine treatment., Outcomes: Two months after surgery the patient reported that the gross hematuria had disappeared, and that the right lumbar discomfort was significantly relieved.Cystoscopy showed no obvious recurrence in the operative area, but magnetic resonance imaging (MRI) suggested recurrence. The patient refused partial cystectomy, and the ureteral stent was removed., Lesson: The clinical manifestations of bladder amyloidosis are nonspecific, and under cystoscopy can be easily confused with bladder tumors. Accurate diagnosis of bladder amyloidosis relies on histopathology. Transurethral resection of bladder tumors or partial cystectomy is an option for surgical treatment; the latter should be performed if the ureteral opening is involved., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)