A gait stability evaluation method based on wearable acceleration sensors.

In this study, an accurate tool is provided for the evaluation of the effect of joint motion effect on gait stability. This quantitative gait evaluation method relies exclusively on the analysis of data acquired using acceleration sensors. First, the acceleration signal of lower limb motion is collected dynamically in real-time through the acceleration sensor. Second, an algorithm based on improved dynamic time warping (DTW) is proposed and used to calculate the gait stability index of the lower limbs. Finally, the effects of different joint braces on gait stability are analyzed. The experimental results show that the joint brace at the ankle and the knee reduces the range of motions of both ankle and knee joints, and a certain impact is exerted on the gait stability. In comparison to the ankle joint brace, the knee joint brace inflicts increased disturbance on the gait stability. Compared to the joint motion of the braced side, which showed a large deviation, the joint motion of the unbraced side was more similar to that of the normal walking process. In this paper, the quantitative evaluation algorithm based on DTW makes the results more intuitive and has potential application value in the evaluation of lower limb dysfunction, clinical training and rehabilitation.

Understanding painful versus non-painful dental pain in female and male patients: A transcriptomic analysis of human biopsies.

Dental pain from apical periodontitis is an infection induced-orofacial pain condition that presents with diversity in pain phenotypes among patients. While 60% of patients with a full-blown disease present with the hallmark symptom of mechanical allodynia, nearly 40% of patients experience no pain. Furthermore, a sexual dichotomy exists, with females exhibiting lower mechanical thresholds under basal and diseased states. Finally, the prevalence of post-treatment pain refractory to commonly used analgesics ranges from 7-19% (∼2 million patients), which warrants a thorough investigation of the cellular changes occurring in different patient cohorts. We, therefore, conducted a transcriptomic assessment of periapical biopsies (peripheral diseased tissue) from patients with persistent apical periodontitis. Surgical biopsies from symptomatic male (SM), asymptomatic male (AM), symptomatic female (SF), and asymptomatic female (AF) patients were collected and processed for bulk RNA sequencing. Using strict selection criteria, our study found several unique differentially regulated genes (DEGs) between symptomatic and asymptomatic patients, as well as novel candidate genes between sexes within the same pain group. Specifically, we found the role of cells of the innate and adaptive immune system in mediating nociception in symptomatic patients and the role of genes involved in tissue homeostasis in potentially inhibiting nociception in asymptomatic patients. Furthermore, sex-related differences appear to be tightly regulated by macrophage activity, its secretome, and/or migration. Collectively, we present, for the first time, a comprehensive assessment of peripherally diseased human tissue after a microbial insult and shed important insights into the regulation of the trigeminal system in female and male patients.

Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice.

Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of both sexes. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naïve as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: (1) FACS sorting obtained higher number of neurons from female trigeminal ganglia (TG) compared to males; (2) Naïve female neurons innervating the tongue expressed immune cell markers such as Csf1R, C1qa and others, that weren't expressed in males. This was validated by Immunohistochemistry. (3) Accordingly, immune cell markers such as Csf1 exclusively sensitized TRPV1 responses in female TG neurons. (4) Male neurons were more tightly regulated than female neurons upon tumor growth and very few differentially expressed genes (DEGs) overlapped between the sexes, (5) Male DEGs contained higher number of transcription factors whereas female DEGs contained higher number of enzymes, cytokines and chemokines. Collectively, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, pathways and molecular function of tongue-innervating sensory neurons.

Combined evaluation of Geriatric nutritional risk index and Neutrophil to lymphocyte ratio for predicting all-cause and cardiovascular mortality in hemodialysis patients.

OBJECTIVE: Malnutrition, accompanied by an inflammatory profile, is a risk factor for poor prognosis in hemodialysis patients. The purpose of this study was to investigate the predictive value of NLR combined with GNRI for all-cause and cardiovascular mortality in hemodialysis patients. METHODS: A total of 240 maintenance hemodialysis (MHD) patients in hemodialysis centers were enrolled in this retrospective study. The influencing factors of all-cause death in hemodialysis patients were analyzed by COX regression. The cut-off values of GNRI and NLR for predicting mortality in enrolled MHD patients were 89.01 and 4, respectively. Based on these cut-off values, the patients were divided into four groups: G1: high GNRI (≥ 89.01) + high NLR (≥ 4) group; G2: high GNRI (≥ 89.01) + low NLR (<4) group, G3: low GNRI (< 89.01) + high NLR (≥4) group; G4: low GNRI (< 89.01) + low NLR (<4). RESULTS: During the follow-up period (average: 58 months), the all-cause mortality was 20.83%(50/240) and the cardiovascular mortality was 12.08%(29/240). Both NLR and GNRI were independent risk factors for the prognosis of MHD patients (P<0.05). Survival analysis showed that patients with low GNRI had a lower survival rate than those with high GNRI, whereas patients with high NLR had a lower survival rate than those with low NLR. Kaplan-Meier curve for all-cause mortality revealed that compared to G1, G2, and G4, G3 had the lowest survival rate, while G2 had the highest survival rate among all groups (P < 0.05). Kaplan-Meier curve for cardiovascular mortality showed that G3 had lower survival than G1, G2, and G4 (P < 0.001). CONCLUSIONS: Our study demonstrates that bothGNRI and NLR are associated with all-cause mortality and cardiovascular mortality in MHD patients. Combining these two factorsmay contribute to a prognostic evaluation for MHD patients.

Value of neutrophil-to-lymphocyte ratio for diagnosing sarcopenia in patients undergoing maintenance hemodialysis and efficacy of Baduanjin exercise combined with nutritional support.

Objective: To investigate the value of neutrophil-to-lymphocyte ratio (NLR) for diagnosing sarcopenia in patients undergoing maintenance hemodialysis (MHD) and efficacy of Baduanjin exercise combined with nutritional support on MHD patients with sarcopenia. Methods: A total of 220 patients undergoing MHD in MHD centers were selected, among which 84 had occurred with sarcopenia confirmed by measurements from the Asian Working Group for Sarcopenia. Data were collected for analyzing the influencing factors that lead to the onset of sarcopenia in MHD patients with the use of one-way analysis of variance and multivariate logistic regression. The role of NLR in the diagnosis of sarcopenia was explored, and its correlation with relevant diagnostic measurement performance such as grip strength, gait speed and skeletal muscle mass index was analyzed. In the end, some 74 patients with sarcopenia that qualify for further intervention and observation standards were divided into observation group (Baduanjin exercise plus nutritional support) and control group (nutritional support only), which were both intervened for 12 weeks. A total of 68 patients finished all interventions, with 33 patients in the observation group and 35 in the control group. The grip strength, gait speed, skeletal muscle mass index as well as the NLR were compared between the two groups. Results: With the employment of multivariate logistic regression analysis, it was found that age, hemodialysis duration and NLR were risk factors for the onset of sarcopenia in MHD patients (P < 0.05). The area under ROC curve for NLR of MHD patients with sarcopenia was 0.695, and NLR was negatively correlated with a biochemical indicator-human blood albumin (P < 0.05). NLR was also negatively correlated with patient's grip strength, gait speed and skeletal muscle mass index, with the same correlation found in sarcopenia patients (all P < 0.05). After intervention, patient's grip strength and gait speed were both higher, and the NLR lower in the observation group than those in the control group (P < 0.05). Conclusion: The occurrence of sarcopenia in MHD patients is associated with patient's age, hemodialysis duration and NLR. Therefore, it has been concluded that NLR has certain values in the diagnosis of sarcopenia in patients undergoing MHD. Moreover, the muscular strength can be enhanced and inflammation decreased in sarcopenia patients through nutritional support and physical exercise, i.e., Bajinduan exercise.

Non-Iterative Multiscale Estimation for Spatial Autoregressive Geographically Weighted Regression Models.

Multiscale estimation for geographically weighted regression (GWR) and the related models has attracted much attention due to their superiority. This kind of estimation method will not only improve the accuracy of the coefficient estimators but also reveal the underlying spatial scale of each explanatory variable. However, most of the existing multiscale estimation approaches are backfitting-based iterative procedures that are very time-consuming. To alleviate the computation complexity, we propose in this paper a non-iterative multiscale estimation method and its simplified scenario for spatial autoregressive geographically weighted regression (SARGWR) models, a kind of important GWR-related model that simultaneously takes into account spatial autocorrelation in the response variable and spatial heterogeneity in the regression relationship. In the proposed multiscale estimation methods, the two-stage least-squares (2SLS) based GWR and the local-linear GWR estimators of the regression coefficients with a shrunk bandwidth size are respectively taken to be the initial estimators to obtain the final multiscale estimators of the coefficients without iteration. A simulation study is conducted to assess the performance of the proposed multiscale estimation methods, and the results show that the proposed methods are much more efficient than the backfitting-based estimation procedure. In addition, the proposed methods can also yield accurate coefficient estimators and such variable-specific optimal bandwidth sizes that correctly reflect the underlying spatial scales of the explanatory variables. A real-life example is further provided to demonstrate the applicability of the proposed multiscale estimation methods.

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice.

Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of both sexes. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naïve as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: 1) Tongue tissue of female mice was innervated with higher number of trigeminal neurons compared to males; 2) Naïve female neurons innervating the tongue exclusively expressed immune cell markers such as Csf1R, C1qa and others, that weren't expressed in males. This was validated by Immunohistochemistry. 4) Accordingly, immune cell markers such as Csf1 exclusively sensitized TRPV1 responses in female TG neurons. 3) Male neurons were more tightly regulated than female neurons upon tumor growth and very few differentially expressed genes (DEGs) overlapped between the sexes, 5) Male DEGs contained higher number of transcription factors whereas female DEGs contained higher number of enzymes, cytokines and chemokines. Collectively, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, pathways and molecular function of tongue-innervating sensory neurons.

Artemisinin suppressed tumour growth and induced vascular normalisation in oral squamous cell carcinoma via inhibition of macrophage migration inhibitory factor.

BACKGROUND: Tumour vascular normalisation therapy advocates a balance between pro-angiogenic factors and anti-angiogenic factors in tumours. Artemisinin (ART), which is derived from traditional Chinese medicine, has been shown to inhibit tumour growth; however, the relationship between ART and tumour vascular normalisation in oral squamous cell carcinoma (OSCC) has not been previously reported. METHODS: Different concentrations(0 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg)of ART were used to treat the xenograft nude mice model of OSCC. The effects of ART on migration and proliferation of OSCC and human umbilical vein endothelial cells (HUVEC) cells were detected by scratch assay and CCK-8 assay. OSCC cells with macrophage migration inhibitory factor (MIF) silenced were constructed to explore the effect of MIF. RESULTS: Treatment with ART inhibited the growth and angiogenesis of OSCC xenografts in nude mice and downregulated vascular endothelial growth factor (VEGF), IL-8, and MIF expression levels. ART reduced the proliferation, migration, and tube formation of HUVEC, as well as the expression of VEGFR1 and VEGFR2. When the dose of ART was 50 mg/kg, vascular normalisation of OSCC xenografts was induced. Moreover, VEGF and IL-8 were needed in rhMIF restoring tumour growth and inhibit vascular normalisation after the addition of rhMIF to ART-treated cells. CONCLUSION: Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF-signalling pathway.

Production of Inhalable Ultra-Small Particles for Delivery of Anti-Inflammation Medicine via a Table-Top Microdevice.

A table-top microdevice was introduced in this work to produce ultrasmall particles for drug delivery via inhalation. The design and operation are similar to that of spray-drying equipment used in industry, but the device itself is much smaller and more portable in size, simpler to operate and more economical. More importantly, the device enables more accurate control over particle size. Using Flavopiridol, an anti-inflammation medication, formulations have been developed to produce inhalable particles for pulmonary delivery. A solution containing the desired components forms droplets by passing through an array of micro-apertures that vibrate via a piezo-electrical driver. High-purity nitrogen gas was introduced and flew through the designed path, which included the funnel collection and cyclone chamber, and finally was pumped away. The gas carried and dried the micronized liquid droplets along the pathway, leading to the precipitation of dry solid microparticles. The formation of the cyclone was essential to assure the sufficient travel path length of the liquid droplets to allow drying. Synthesis parameters were optimized to produce microparticles, whose morphology, size, physio-chemical properties, and release profiles met the criteria for inhalation. Bioactivity assays have revealed a high degree of anti-inflammation. The above-mentioned approach enabled the production of inhalable particles in research laboratories in general, using the simple table-top microdevice. The microparticles enable the inhalable delivery of anti-inflammation medicine to the lungs, thus providing treatment for diseases such as pulmonary fibrosis and COVID-19.

Pancreatic extracorporeal shock wave lithotripsy for a patient concurrent with autosomal dominant polycystic kidney disease: a case report.

Whether pancreatic extracorporeal shock wave lithotripsy (ESWL) is safe for patients with autosomal dominant polycystic kidney disease (ADPKD) is unclear. A woman in her early 30s was admitted to our hospital because of intermittent upper abdominal pain and recurrent pancreatitis. The imaging results confirmed the diagnosis of pancreatic stones and ADPKD. We performed pancreatic ESWL using a third-generation lithotripter to pulverize the pancreatic stones. A maximum of 5000 shock waves was delivered per therapeutic session. A second session of ESWL was performed the next day. The patient developed no adverse events or complications related to pancreatic ESWL. Three years after treatment, the patient had developed no relapse of pancreatitis or abdominal pain. Shock waves do not lead to complications such as hematuria, cyst rupture, or deterioration of the inner bleeding of renal cysts. Multiple kidney cysts are not a contraindication for pancreatic ESWL.

Community-based multiple screening for metabolic syndrome by innovative theory: A longitudinal study.

The purpose of this research is to elucidate whether metabolic syndrome affects the rate of adoption of a new multiple cancer screening programme, based on the Diffusion of Innovation theory. The time to attend the screening programme, conducted in Keelung, Taiwan, within 10 years was assessed by innovativeness (innovators, early adaptors, early majority, late majority and laggard) using data from 79,303 residents, with the information on metabolic syndrome accrued from routine adult health check-ups. The median time of adopting the programme and the relative rates of early adoption by metabolic syndrome and its severity score were estimated. The results show that the estimated times to adopt the programme ranged from 3 months for innovators to 10 years for the laggard. The rate of early adoption was 34% higher for participants without metabolic syndrome than for those with the disease, and the gradient relationship of disease severity was noted. The adjusted median time to adopt innovativeness was 0.82 years earlier for participants who were disease-free than those with the disease. Meanwhile, the adjusted median time was wider by up to 2.25 years for those with severe disease. The study suggests that innovation should prioritise the potential risk of the metabolic syndrome population.

A preliminary study of current situation and competences of doctoral nursing education in Taiwan: A multi-methods research design.

AIM: To explore the status and overall competency of Taiwan's doctoral nursing programs. BACKGROUND: Taiwan has 11 universities offer doctoral degree programs in nursing from 1997 to 2020. As the demand for educators of higher nursing education increases, whether the nursing talent requirements have been satisfactorily fulfilled. DESIGN: A two-stage data collection based on a multi-methods survey was conducted. METHODS: The first stage from December 2017 to the end of December 2019, involved collecting admission brochures for 12 doctoral nursing programs provided by 11 universities and 14 Internet databases. In the second stage, convenience sampling was performed to recruit 115 graduates of national doctoral nursing programs to collect data through a self-administered questionnaire online survey from July to the end of September 2018. RESULTS: A systematic review of the vision and core competencies of each university revealed a general emphasis on nursing knowledge, research, leadership, international perspective and competence, innovation, social practice and policy. More specifically, universities aim to cultivate five core competencies in students, for example, nursing knowledge, scientific and innovative research capabilities and participation in the formulation and promotion of nursing policies. Of the 115 graduates of national doctoral nursing programs surveyed, the online questionnaire revealed that more than half of the respondents were aged 41-50 years (n = 62, 53.9%), 81.8% occupied a teaching position and most had 2.4-9.8 years of study in the program (mean = 6.09 ± 1.81 years). Respondents who completed a doctoral nursing program in Taiwan could learn orderly teaching, research and leadership capabilities with scored 4.12, 4.11 and 3.65, respectively. CONCLUSIONS: The overall orientation of the doctoral nursing programs in Taiwan aligns approximately with global trends in nursing. This study suggests that international and national resources should be incorporated into the cultivation of various competencies and curriculum quality control; moreover, industry, academia and the government should hold regular meetings to formulate suitable evaluation mechanisms.

Reinforced nitrite supplement by cathode nitrate reduction with a bio-electrochemical system coupled anammox reactor.

Anammox has been widely used for the treatment of nitrogen wastewater. However, the problem of stable NO2- supplement becomes one of the limiting factors. It is an effective method to obtain NO2- by denitrifying the NO3-, including the by-product of Anammox. In this study, NO2- was reinforced by bio-electrochemical system (BES) through the reaction of partial denitrification in situ in an Anammox reactor. Our results showed that both NO3- and NO2- can be reduced on the cathode with different Coulombic efficiencies. The reduction of NO3- amount increased with an increase in Inf-NO3-, which was greater than that of NO2-. The conversion amount of NO3- was 2.50% ± 17.25% to the theoretical Eff-NO3-, and the maximum reduction amount was 23.24% with the highest Coulombic efficiency of 3.56%. High throughput results showed that denitrifying bacteria, such as Limnobacter, Thauera, Denitratisoma, Nitrosomonas and Nitrospira, were attached to the cathode surface and in Anammox granular sludge. This study showed that NO2- can be supplied by reducing the by-product NO3- with denitrification cathode at Anammox environment in-situ.

Oral squamous cell carcinoma-released brain-derived neurotrophic factor contributes to oral cancer pain by peripheral tropomyosin receptor kinase B activation.

ABSTRACT: Oral cancer pain is debilitating and understanding mechanisms for it is critical to develop novel treatment strategies treatment strategies. Brain-derived neurotrophic factor (BDNF) signaling is elevated in oral tumor biopsies and is involved with tumor progression. Whether BDNF signaling in oral tumors contributes to cancer-induced pain is not known. The current study evaluates a novel peripheral role of BDNF-tropomyosin receptor kinase B (TrkB) signaling in oral cancer pain. Using human oral squamous cell carcinoma (OSCC) cells and an orthotopic mouse tongue cancer pain model, we found that BDNF levels were upregulated in superfusates and lysates of tumor tongues and that BDNF was expressed by OSCC cells themselves. Moreover, neutralization of BDNF or inhibition of TrkB activity by ANA12, within the tumor-bearing tongue reversed tumor-induced pain-like behaviors in a sex-dependent manner. Oral squamous cell carcinoma conditioned media also produced pain-like behaviors in naïve male mice that was reversed by local injection of ANA12. On a physiological level, using single-fiber tongue-nerve electrophysiology, we found that acutely blocking TrkB receptors reversed tumor-induced mechanical sensitivity of A-slow high threshold mechanoreceptors. Furthermore, single-cell reverse transcription polymerase chain reaction data of retrogradely labeled lingual neurons demonstrated expression of full-form TrkB and truncated TrkB in distinct neuronal subtypes. Last but not the least, intra-TG siRNA for TrkB also reversed tumor-induced orofacial pain behaviors. Our data suggest that TrkB activities on lingual sensory afferents are partly controlled by local release of OSCC-derived BDNF, thereby contributing to oral cancer pain. This is a novel finding and the first demonstration of a peripheral role for BDNF signaling in oral cancer pain.

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Metabolic bone disease of prematurity (MBDP) is a systemic bone disease with a reduction in bone mineral content due to disorder of calcium and phosphorus metabolism. There is still a lack of in-depth research and systematic understanding of MBDP in China, and there are many irregularities in clinical management of this disease. Based on relevant studies in China and overseas, Grading of Recommendations Assessment, Development and Evaluation was used to develop the expert consensus on the clinical management of MBDP, which provides recommendations from the following five aspects: high-risk factors, screening/diagnosis, prevention, treatment, and post-discharge follow-up of MBDP, so as to provide relevant practitioners with recommendations on the clinical management of MBDP to reduce the incidence rate of MBDP and improve its short- and long-term prognosis.

Proton resonance frequency-based thermometry for aqueous and adipose tissues.

PURPOSE: The proton resonance frequency (PRF)-based thermometry uses heating-induced phase variations to reconstruct magnetic resonance (MR) temperature maps. However, the measurements of the phase differences may be corrupted by the presence of fat due to its phase being insensitive to heat. The work aims to reconstruct the PRF-based temperature maps for tissues containing fat. METHODS: This work proposes a PRF-based method that eliminates the fat's phase contribution by estimating the temperature-insensitive fat vector. A vector in a complex domain represents a given voxel's magnetization from an acquired, complex MR image. In this method, a circle was fit to a time series of vectors acquired from a heated region during a heating experiment. The circle center served as the fat vector, which was then subtracted from the acquired vectors, leaving only the temperature-sensitive vectors for thermal mapping. This work was verified with the gel phantoms of 10%, 15%, and 20% fat content and the ex vivo phantom of porcine abdomen tissue during water-bath heating. It was also tested with an ex vivo porcine tissue during focused ultrasound (FUS) heating. RESULTS: A good agreement was found between the temperature measurements obtained from the proposed method and the optical fiber temperature probe in the verification experiments. In the gel phantoms, the linear regression provided a slope of 0.992 and an R2 of 0.994. The Bland-Altman analysis gave a bias of 0.49°C and a 95% confidence interval of ±1.60°C. In the ex vivo tissue, the results of the linear regression and Bland-Altman methods provided a slope of 0.979, an intercept of 0.353, an R2 of 0.947, and a 95% confidence interval of ±3.26°C with a bias of -0.14°C. In FUS tests, a temperature discrepancy of up to 28% was observed between the proposed and conventional PRF methods in ex vivo tissues containing fat. CONCLUSIONS: The proposed PRF-based method can improve the accuracy of the temperature measurements in tissues with fat, such as breast, abdomen, prostate, and bone marrow.

Expression of Ki-67, Cyclin D1, P53, and P16 in patients with oral leukoplakia and leukoplakia cancerization with spicy diet in Chengdu.

OBJECTIVES: To investigate the expression of Ki-67, Cyclin D1, P53, and P16 in patients with oral leukoplakia (OLK) and OLK cancerization who have aspicy diet in Chengdu. METHODS: Thirtypatients with OLK andspicy diet and 15 patients with OLK without spicy diet in Chengdu were divided into three groups: hyperplastic OLK (OLK-), OLK with mild to moderate dysplasia (OLK+), and severe dysplastic  OLK or oral squamous cell carcinoma (OSCC) transforming from OLK (OLK++/OSCC). The expression of Ki-67, Cyclin D1, P53, and P16 were detected by immunohistochemistry and statistically analyzed. RESULTS: The expression of Ki-67 and P53 in patients with or without spicy diet in the OLK+and OLK++/OSCC groups were stronger than that of the OLK- group (P<0.05). The OLK++/OSCC group showed a higher expression of Cyclin D1 and lower expression of P16 than the OLK- group (P<0.05). The expression of Ki-67, Cyclin D1, P53, and P16 in patients with spicy diet and without spicy diet had no substantial difference. The expression of Ki-67 and Cyclin D1 showed a positive correlation (r=0.439, P=0.015). CONCLUSIONS: Spicy diet did not have an influence on the expression of Ki-67, Cyclin D1, P53, and P16 in patients with OLK and OSCC. The expression of Ki-67, Cyclin D1, and P53 increased with the development of OLK, whereas P16 showed opposite expression trend.

Effect of Statins on Renal Function and Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary nephropathy with few treatments to slow renal progression. The evidence on the effect of lipid-lowering agents (statins) on ADPKD progression remains inconclusive. METHODS: We performed a systematic review and meta-analysis by searching the PubMed, Embase, Web of Science, and Cochrane databases (up to November 2019). Changes in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) were the primary outcomes. Mean differences (MDs) for continuous outcomes and 95% confidence intervals (CIs) were calculated by a random-effects model. RESULTS: Five clinical studies with 648 participants were included. Statins did not show significant benefits in the yearly change in eGFR (4 studies, MD = -0.13 mL/min/m2, 95% CI: -0.78 to 0.52, p = 0.70) and the yearly change in TKV (3 studies, MD = -1.17%, 95% CI: -3.40 to 1.05, p = 0.30) compared with the control group. However, statins significantly decreased urinary protein excretion (-0.10 g/day, 95% CI: -0.16 to -0.03, p = 0.004) and serum low-density lipoprotein level (-0.34 mmol/L, 95% CI: -0.58 to -0.10, p = 0.006). CONCLUSION: Despite these proteinuria and lipid-lowering benefits, the effect of statins on ADPKD progression was uncertain.

The Evolving Landscape of PD-1/PD-L1 Pathway in Head and Neck Cancer.

Over the past 10 years, cancer immunotherapy has made significant progress in multiple cancer types and has been gradually been applied to clinical cancer care, in which the programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is one of the most attractive targets. Compared with traditional therapies, the emerging PD-1/PD-L1 blockade immunotherapy exhibited more satisfactory curative effects and lower toxicity for patients with advanced head and neck squamous cell carcinoma (HNSCC). This review analyzes the expression characteristics and clinical significance of PD-1/PD-L1 in HNSCC, the immunosuppressive roles of tumor cell and stromal cell expressing PD-1/PD-L1 in this disease, and presents the development landscape of PD-1/PD-L1 inhibitors, which may provide new curative alternatives for recurrent or metastatic HNSCC.