As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

BACKGROUND: With the ongoing worldwide coronavirus disease 2019 (COVID-19) pandemic, an increasing number of viral variants are being identified, which poses a challenge for nucleic acid-based diagnostic tests. Rapid tests, such as real-time reverse transcription-polymerase chain reaction (rRT-PCR), play an important role in monitoring COVID-19 infection and controlling its spread. However, the changes in the genotypes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in decreased sensitivity of the rRT-PCR assay and it is necessary to monitor the mutations in primers and probes of SARS-CoV-2 detection over time. METHODS: We developed two rRT-PCR assays to detect the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) genes of SARS-CoV-2. We evaluated these assays together with our previously published assays targeting the ORF1ab and N genes for the detection and confirmation of SARS-CoV-2 and its variants of concern (VOCs). In addition, we also developed two rRT-PCR assays (S484K and S501Y) targeting the spike gene, which when combined with the open reading frames (ORF)1ab assay, respectively, to form duplex rRT-PCR assays, were able to detect SARS-CoV-2 VOCs (lineages B.1.351 and B.1.1.7). RESULTS: Using a SARS-CoV-2 stock with predetermined genomic copies as a standard, the detection limit of both assays targeting RdRp and N was five copies/reaction. Furthermore, no cross-reactions with six others human CoVs (229E, OC43, NL63, HKU1, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus) were observed using these assays. In addition, the S484K and S501Y assays were combined with the ORF1ab assay, respectively. CONCLUSIONS Four rRT-PCR assays (RdRp, N, S484K, and S501Y) were used to detect SARS-CoV-2 variants, and these assays were shown to be effective in screening for multiple virus strains.
COVID-19 ; Humans ; RNA, Viral/genetics* ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; SARS-CoV-2 ; Sensitivity and Specificity

Bronchoalveolar Lavage Fluid/virology* ; COVID-19/virology* ; Feces/virology* ; Genome, Viral ; Humans ; Mouth Mucosa/virology* ; Multiplex Polymerase Chain Reaction ; Nasal Mucosa/virology* ; SARS-CoV-2/genetics* ; Sputum/virology* ; Whole Genome Sequencing

Objective:To investigate the action mechanism of Yinchenhao Tang against type 2 diabetes mellitus （T2DM） complicated with non-alcoholic fatty liver disease （NAFLD） in MKR mice. Method:Forty eight-week-old MKR mice were fed a high-fat diet for eight weeks and then divided into the model group，original Yinchenhao Tang （17.16 g·kg^-1） group，Yinchenhao Tang group at a specified dose （4.68 g·kg^-1） in teaching materials，and positive drug ［metformin + simvastatin， （65+2.6）×10^-3 g·kg^-1］ group. Another 10 MKR mice of the same age were classified into the blank group and 10 FVB mice into the normal group. After eight weeks of intragastric administration in each group，the liver wet weight，oral glucose tolerance test （OGTT），serum inflammatory factors interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α），and changes in blood lipid and liver function were determined. Hematoxylin-eosin （HE） staining was conducted for observing the morphological changes in liver tissue under a transmission electron microscope，followed by the detection of Toll-like receptor 4 （TLR4），myeloid differentiation factor 88 （MyD88），and nuclear transcription factor-κB （NF-κB） protein expression by Western blot. Result:Compared with the model group，the medication groups exhibited significantly reduced liver wet weight index （P<0.01），improved OGTT result （P<0.05），and down-regulated serum IL-6 and TNF-α levels （P<0.01）. In terms of morphological changes，Yinchenhao Tang protected the hepatocyte structure and alleviated hepatocyte steatosis. Moreover， Yinchenhao Tang obviously down-regulated the protein expression levels of TLR4，MyD88，and NF-κB in liver tissue of MKR mice with T2DM combined with NAFLD （P<0.05），and the down-regulation of TLR4 and NF-κB in the original Yinchenhao Tang group was better than that in the Yinchenhao Tang group at a specified dose in teaching materials （P<0.05）. Conclusion:Yinchenhao Tang is able to reduce inflammatory factor levels and down-regulate TLR4，MyD88，and NF-κB expression in liver tissue to relieve the pathological liver injury and interfere with T2DM combined with NAFLD of MKR mice. It exerts a certain liver-protective effect by lowering the blood lipids and delaying the hepatic inflammation.

【Objective】 To explore the attention and its relationship with anxiety in patients with glaucoma.【Methods】A prospective case-control study was done on 20 primary open angle glaucoma（POAG）patients and 28 normal subjects. Response time with and without disturbance was examined by using Matlab software. Anxiety was assessed with State Anxiety Inventory（S- AI）and Trait Anxiety Inventory（T- AI）. Response time and inhibiting effects between two groups were compared by t test and Mann- Whitney U test ，respectively. Spearman correlation analysis was applied to determine the relationship between inhibiting effect and anxiety.【Results】The scores of S-AI and T-AI in POAG group were significantly higher than those in normal subjects（t = -3.912，P = 0.001；t = -2.127，P = 0.042）. There were statistically significant differences in the scores between groups even after gender was adjusted by using line regression model（β = 9.449，P = 0.000；β = 7.089，P = 0.018）. The average response time in POAG group（0.84±0.15）s was significantly longer than that in normal participants（0.75±0.14）s（t = -2.127，P = 0.039）. The difference was statistically insignificant when gender was adjusted by using line regression model（β = 0.063，P = 0.210）. The inhibiting effect in POAG group（0.126±0.089）s was longer than that in normal subjects（0.085±0.066）s（Z = -1.715，P = 0.086）. The inhabiting effect wasn′ t statistically significantly correlated with scores of S- AI and T- AI（P＞0.05）.【Conclusions】Patients with POAG showed severer anxiety than normal subjects but attention was comparable. There was no significant correlation between attention and anxiety.

Objective:To explore the surgical experience of high speed rotary excision combined with multi-technology in the treatment of adult nape-fat-pad.Methods:A total of 83 patients with nape-fat-pad in our department from March 2016 to September 2019 were selected for the study. In this marked area, 0. 2 percent lidocaine with 1∶10 000 epinephrine was used for local tumescent anesthesia, then a skin incision of about 0.5 cm was made directly under the fat pad and/or about 2 cm from it. First, use a fork knife to separate the fat pad at multiple planes and angles, then cut off with a rotary excision and sucked out thoroughly. Second, use a thin liposuction tube to pump the transition area between the nape-fat-pad and normal fat until the transition is natural and smooth. Finally, fix the skin in the separation area with oil nail, apply pressure with "8-form" bandage and sleep on the rice pillow for 1 week after surgery. The appearance of the neck, postoperative complications and patient satisfaction were followed up 3-6 months after the operation.Resuts:83 patients had varying degrees of pain and swelling for 1-2 months after operation, 76 cases(91.57%) of the patients had complete disappearance of swelling in about 1 month, 12 cases(14.46%)had cyanosis and ecchymosis, which improved in about 3 weeks, 5 cases(6.02%) had a sense of subcutaneous cord or induration, and recovered completely in 2-3 months. Subcutaneous effusion was found in 2 patients(2.41%) in the early stage of operation and absorbed about 1 week.4 cases (4.82%) had a slight "sense of step" in the operative and normal fat transition area about 1 month after operation. 3 cases (3.61%)had poor wound healing, and the other 80 cases (96.39%)were grade A healing. There was no abnormal skin sensation in the operation area in all the 83 cases.No serious complications such as skin necrosis infection and important vascular injury occurred in all the patients 3 to 6 months after the operation. In the patient satisfaction survey, 70 patients were satisfied, 9 were satisfied, 4 were average, the satisfaction rate of the patients was 95.18%.Conclusions:The high speed rotary excision combined with multi-technology in the treatment of nape-fat-pad has short operation time, good curative effect, few complications and high patient satisfaction.

Objective:To explore the surgical experience of high speed rotary excision combined with multi-technology in the treatment of adult nape-fat-pad.Methods:A total of 83 patients with nape-fat-pad in our department from March 2016 to September 2019 were selected for the study. In this marked area, 0. 2 percent lidocaine with 1∶10 000 epinephrine was used for local tumescent anesthesia, then a skin incision of about 0.5 cm was made directly under the fat pad and/or about 2 cm from it. First, use a fork knife to separate the fat pad at multiple planes and angles, then cut off with a rotary excision and sucked out thoroughly. Second, use a thin liposuction tube to pump the transition area between the nape-fat-pad and normal fat until the transition is natural and smooth. Finally, fix the skin in the separation area with oil nail, apply pressure with "8-form" bandage and sleep on the rice pillow for 1 week after surgery. The appearance of the neck, postoperative complications and patient satisfaction were followed up 3-6 months after the operation.Resuts:83 patients had varying degrees of pain and swelling for 1-2 months after operation, 76 cases(91.57%) of the patients had complete disappearance of swelling in about 1 month, 12 cases(14.46%)had cyanosis and ecchymosis, which improved in about 3 weeks, 5 cases(6.02%) had a sense of subcutaneous cord or induration, and recovered completely in 2-3 months. Subcutaneous effusion was found in 2 patients(2.41%) in the early stage of operation and absorbed about 1 week.4 cases (4.82%) had a slight "sense of step" in the operative and normal fat transition area about 1 month after operation. 3 cases (3.61%)had poor wound healing, and the other 80 cases (96.39%)were grade A healing. There was no abnormal skin sensation in the operation area in all the 83 cases.No serious complications such as skin necrosis infection and important vascular injury occurred in all the patients 3 to 6 months after the operation. In the patient satisfaction survey, 70 patients were satisfied, 9 were satisfied, 4 were average, the satisfaction rate of the patients was 95.18%.Conclusions:The high speed rotary excision combined with multi-technology in the treatment of nape-fat-pad has short operation time, good curative effect, few complications and high patient satisfaction.

BACKGROUND AND PURPOSE: It is essential to develop a reliable predictive serum biomarker for Parkinson's disease (PD). The accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. The purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. METHODS: Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. RESULTS: The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutoff age than in the group above the cutoff age. CONCLUSIONS: Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.
alpha-Synuclein ; Humans ; Multiple System Atrophy ; Parkinson Disease ; ROC Curve ; Supranuclear Palsy, Progressive

INTRODUCTIONPatients with metastatic nasopharyngeal carcinoma (NPC) have variable survival outcomes. We have previously shown that an elevated peripheral blood lymphocyte-to-monocyte ratio (LMR) is associated with an increased metastatic risk in patients with primary NPC. The present study aimed to investigate the prognostic value of pretreatment LMR in a large cohort of metastatic NPC patients.

METHODSClinical data of 672 patients with metastatic NPC diagnosed between January 2003 and December 2009 were analyzed. The peripheral lymphocyte and monocyte counts were retrieved, and LMR was calculated. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate COX proportional hazards analyses were performed to evaluate the association of LMR with overall survival (OS).

RESULTSUnivariate analysis revealed that an elevated absolute lymphocyte count (≥1.390×10(9)/L) and LMR (≥2.475) as well as a decreased monocyte count (<0.665×10(9)/L) were significantly associated with prolonged OS. Multivariate Cox proportional hazard analysis showed that LMR (hazard ratio [HR]=0.50, 95% confidence interval [CI]=0.41-0.60, P<0.001), absolute lymphocyte count (HR=0.77, 95% CI=0.64-0.93, P=0.007), and monocyte count (HR=1.98, 95% CI=1.63-2.41, P<0.001) were independent prognostic factors. By stratification analyses, only LMR remained a significant predictor of prognosis.

CONCLUSIONWe identified pretreatment LMR as an independent prognostic factor for patients with metastatic NPC. Independent validation of our findings is needed.

Introduction:Patients with metastatic nasopharyngeal carcinoma (NPC) have variable survival outcomes. We have previously shown that an elevated peripheral blood lymphocyte-to-monocyte ratio (LMR) is associated with an increased metastatic risk in patients with primary NPC. The present study aimed to investigate the prognostic value of pretreatment LMR in a large cohort of metastatic NPC patients. Methods:Clinical data of 672 patients with metastatic NPC diagnosed between January 2003 and December 2009 were analyzed. The peripheral lymphocyte and monocyte counts were retrieved, and LMR was calculated. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate COX proportional hazards analyses were performed to evaluate the association of LMR with overall survival (OS). Results:Univariate analysis revealed that an elevated absolute lymphocyte count (≥1.390 × 109/L) and LMR (≥2.475) as well as a decreased monocyte count (<0.665 × 109/L) were significantly associated with prolonged OS. Multivariate Cox proportional hazard analysis showed that LMR (hazard ratio [HR]=0.50, 95%confidence interval [CI]=0.41–0.60, P<0.001), absolute lymphocyte count (HR=0.77, 95%CI=0.64–0.93, P=0.007), and monocyte count (HR=1.98, 95%CI=1.63–2.41, P<0.001) were independent prognostic factors. By stratification analyses, only LMR remained a significant predictor of prognosis. Conclusion:We identified pretreatment LMR as an independent prognostic factor for patients with metastatic NPC. Independent validation of our findings is needed.