Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Objective:To assess the utility of whole-genome sequencing (WGS) in predicting Mycobacterium tuberculosis resistance to fluoroquinolones (FQs) and to establish a quantitative relationship between resistant gene mutations and resistance levels. Methods:A total of 296 drug-resistant tuberculosis surveillance strains with various resistance profiles, preserved by the National Tuberculosis Reference Laboratory of the Tuberculosis Prevention and Control Center at the Chinese Center for Disease Control and Prevention between 2013 and 2020, were included as study subjects. The Sensititre? MYCOTBI microplate method and WGS were used to assess the phenotypic and genotypic drug sensitivity of Mycobacterium tuberculosis to ofloxacin and moxifloxacin. Sensitivity, specificity, and concordance (Kappa value) of WGS in predicting fluoroquinolone sensitivity were calculated using phenotypic drug susceptibility testing (DST) results as the gold standard. A summary analysis was conducted on the distribution of drug resistance mutation sites and resistance levels. The paired χ 2 test was used to compare the detection rates between the two methods, with P<0.05 indicating statistical significance. Results:Among the 296 Mycobacterium tuberculosis strains with different resistance profiles, 196 were rifampicin-resistant, 50 were resistant to other drugs, and 50 were fully sensitive. WGS identified 81 strains carrying FQs resistance-related mutations, primarily at gyrA codons 94, 90, and 91. Sensitivity, specificity, and consistency (Kappa value) of WGS in predicting ofloxacin resistance were 86.5%, 98.1%, and 0.87, respectively. For moxifloxacin resistance prediction, these values were 80.0%, 99.5%, and 0.83, respectively. There was no statistically significant difference between the phenotypic DST and WGS detection rates for ofloxacin resistance (30.1% vs 27.4%, χ 2=3.06, P=0.08). However, the phenotypic DST detection rate for moxifloxacin resistance (33.8%, 100/296) was significantly higher than that of WGS (27.4%, 81/296) (χ 2=15.43, P<0.01). Analysis of the distribution of resistance mutation sites and resistance levels showed that different mutation sites corresponded to different minimum inhibitory concentrations (MICs). Multiple mutation combinations, including gyrA_D94G, gyrA_D94Y, and gyrA_D94N were mainly associated with high-level resistance, while gyrA_D94A, gyrA_A90V, and gyrA_S91P were primarily linked to low-level resistance. Conclusion:WGS demonstrates favorable sensitivity, specificity, and consistency in predicting FQs resistance and can partially predict resistance levels.

Objective:To use inductively coupled plasma mass spectrometry(ICP-MS)to screen biomarkers of element omics of thyroid cancer,and to establish a risk assessment model of element omics of thyroid cancer,so as to provide a basis for the diagnosis and treatment of thyroid cancer.Methods:A total of 200 patients with thyroid cancer who admitted to Beijing Tongren Hospital from February to November 2020 were selected as the thyroid cancer group,and 50 healthy volunteers who underwent physical examinations at hospital during the same period were selected as the healthy control group.The total amount of 28 trace elements,including iodine(I),calcium(Ca),iron(Fe),nickel(Ni),copper(Cu),zinc(Zn),selenium(Se),antimony(Sb),etc.,in their serum were determined by ICP-MS.The content of trace element,thyroid function,free triiodothyronine(FT3),free tetraiodothyronine(FT4),triiodothyronine(T3),tetraiodothyronine(T4),and thyroid volume of ultrasound examination of were analyzed,and then,a risk assessment model of elemental omics of thyroid diseases was established.Results:There were statistically significant differences in the contents of eight trace elements,including I,Ca,Fe,Ni,Cu,Zn,Se and Sb between the thyroid cancer group and the healthy control group(U=2.601,1.972,2.607,2.611,2.603,2.605,2.601,2.605,P<0.05),respectively.The I,Cr and Mn levels of female patients with thyroid cancer appeared increase,while there were significant differences in I,Mn,Fe,Ni,Cu,Zn,Se and Sb contents of male patients between the thyroid cancer group and the health control group(U=2.601,2.608,2.603,2.602,1.973,2.603,2.601,2.602,P<0.05),respectively.In thyroid cancer group,the FT3,FT4,T3,T4 correlated with I content(r=06209,0.5116,0.557,0.5923,P<0.05),respectively.There were correlations in the concentrations between Fe and Zn,between Cr and Mn,between Ca and Zn,between Se and Fe,and between Zn and Se in the thyroid cancer group(r=0.5523,0.5528,0.7158,0.5699,0.6371,0.5420,P<0.05),respectively.High concentrations of I and Mn were risk factors for thyroid cancer.The specificity and sensitivity of the risk assessment model of elemental omics of thyroid cancer were all larger than 95%.Conclusion:In patients with thyroid cancer,both of the serum Ca of female patients and serum Fe of male patients play important role besides cobalt(Co),Ni,Cu,Zn,Se and Sb play role,which can provide basis for the diagnosis and treatment of thyroid cancer.The risk assessment model based on elemental omics of thyroid cancer has favorable diagnostic performance.

Objective:To investigate the serum metabolites and their metabolic characteristics of patients with optic neuritis.Methods:Case-control study. From January 2021 to January 2022, 9 serum specimens of diagnosed patients with optic neuritis were collected in Department of Neurology from Beijing Tongren Hospital and 9 healthy subjects as the control. Among them, there were 5 females and 4 males in the optic neuritis group, aged (35.8±12.9) years; there were 5 females and 4 males in the healthy control group, aged (32.6±8.6) years. Liquid chromatography-mass spectrometry was used to detect metabolites in serum of healthy control and patients with optic neuritis. The principal component analysis (PCA) and orthogonal partial least-squares discriminination analysis (OPLS-DA) were used to analyze the differential metabolites . The variable importance projection value of OPLS-DA model and the P value of t-test was applied to find the different metabolites. Results:Thirty-seven metabolites were finally identified from serum samples. Four metabolites with variable important in projection (VIP) values larger than 1 and P values less than 0.05 were teased out, three metabolites, LysoPC (P-16∶0), LysoPC (16∶0), LysoPC (P-18∶0) belonge to phospholipid and one metabolite was L-Threonine, they were all down-regulated. The area under curve were 0.951, 0.889, 0.963 and 0.944, respectively. Conclusion:Based on metabonomic analysis, some metabolites in serum have changed, which can provide basis for biomarkers screening of optic neuritis.

Collagen contains abundant cell binding motifs, which are conducive to adhesion, migration, and differentiation, maintain cell vitality and promote cell proliferation. However, pure collagen hydrogel has some shortcomings such as poor mechanical properties, poor thermal stability and fast degradation. Numerous studies have shown that the properties of collagen can be improved by combining it with natural polysaccharides such as alginate, chitosan, hyaluronic acid and cellulose. In this paper, the research status and biological application fields of four kinds of composite hydrogels, including collagen-alginate composite hydrogels, collagen-chitosan hydrogels, collagen-hyaluronic acid hydrogels and collagen-cellulose hydrogels, were summarized. The common preparation methods of four kinds of composite hydrogels were introduced, and the future development direction of collagen-based composite hydrogels was prospected.
Hydrogels/chemical synthesis* ; Collagen/chemistry* ; Polysaccharides/chemistry* ; Alginates/chemistry* ; Hyaluronic Acid/chemistry* ; Chitosan/chemistry* ; Biocompatible Materials/chemistry* ; Humans ; Tissue Engineering/methods* ; Cellulose/chemistry* ; Tissue Scaffolds

Objective:To investigate the relationship between KRAS gene mutation, programmed death receptor ligand 1 (PD-L1) expression and prognosis of first-line concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer.Methods:The clinical data of 50 patients with locally advanced non-small cell lung cancer who were admitted to Nanping First Hospital from January 2018 to December 2021 were retrospectively analyzed. All patients were treated with first-line concurrent chemoradiotherapy. Tissue samples of patients were obtained and paraffin embedded before treatment. Real-time fluorescence quantitative polymerase chain reaction was used to detect the type of KRAS gene mutation in tissues before treatment, and the expression of PD-L1 was determined by immunohistochemistry (the percentage of positive cells in tumor cells ≥1% was positive), and the relationship between KRAS gene status, PD-L1 expression and clinical characteristics and short-term efficacy of patients was analyzed. Patients were followed up for 1 year, and progression-free survival (PFS) curves were plotted by Kaplan-Meier method, and log-rank test was used for comparison. Univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors of PFS.Results:Among the 50 patients, 11 (22.00%) were KRAS mutant, and 36 (72.00%) were PD-L1 positive. Among the 11 patients with KRAS mutation, there were 2 cases of codon 13 mutation and 9 cases of codon 12 mutation in exon 2. The objective response rate (ORR) and clinical control rate (DCR) were 76.00% (38/50) and 86.00% (43/50). There were no significant differences in patients' age, pathological type, TNM stage, ORR and DCR between KRAS mutant group and KRAS wild type group (all P > 0.05). The proportions of male patients [72.73% (8/11) vs. 38.46% (15/39)], patients with smoking history [90.91% (10/11) vs. 20.51% (8/39)] and patients with PD-L1 positive expression [100.00% (11/11) vs. 64.10% (25/39)] in KRAS mutant group were higher than those in KRAS wild type group (all P < 0.05). There were no significant differences in patients' age, pathological type, gender, smoking history, TNM stage, ORR and DCR between PD-L1 positive group and PD-L1 negative group (all P > 0.05). The median PFS time of patients in KRAS mutant group and wild type group was 8.75 and 11.32 months, and the difference in PFS between the two groups was statistically significant ( P = 0.039). The median PFS time of patients with PD-L1 positive and negative was 10.19 and 11.16 months, and there was no statistical significance in PFS between the two ( P = 0.116). Multivariate Cox regression analysis showed that KRAS gene mutation was an independent risk factor for PFS in patients with locally advanced NSCLC after first-line concurrent chemoradiotherapy ( HR = 1.449, 95% CI 1.071-1.196, P = 0.017). PD-L1 expression, smoking history and gender were not independent influencing factors for PFS (all P > 0.05). Conclusions:KRAS gene status is closely related to the prognosis of patients with locally advanced non-small cell lung cancer treated with first-line concurrent chemoradiotherapy, while PD-L1 expression is not.

Objective To explore the value of MRI in assessing regional invasion and neural spread of sinonasal and nasopharyngeal adenoid cystic carcinoma(ACC).Methods A retrospective collection of MRI and clinical data was analyzed in 22 patients with sinonasal and nasopharyngeal ACC confirmed by pathology.Results A total of 22 patients were included in the study.Invasion of the pterygopalatine fossa was observed in 15 cases,involvement of the masticatory muscles in 13 cases,skull base involvement in 13 cases,infiltration of the cavernous sinus in 9 cases,involvement of the infraorbital fissure in 9 cases,orbital involvement in 5 cases,and intracranial involvement in 6 cases.Only 3 patients presented with cranial nerve symptoms.MRI revealed thickening and enhancement of cranial nerves in 10 cases,with involvement of the maxillary and mandibular(V2,V3)branches of the trigeminal nerve(V)in 9 cases,and muscle denervation caused by nerve damage in 6 cases.Among the 12 patients who underwent surgery,9 cases were confirmed to have neural invasion by pathology,with MRI showing cranial nerve alterations in 7 cases of them,one case showed tumor involvement from the pterygopalatine fossa and medial pterygoid muscle to the cavernous sinus and Meckel cavity,while the other case showed tumor involvement from the pterygopalatine fossa to the sphenopalatine foramen.During the follow-up after treatment,4 of 11 patients experienced recurrence,all of which were accompanied by lung metastasis and pre-treatment neural invasion.Conclusion Sinonasal and nasopharyngeal ACC is characterized by a tendency for neural spread,extensive local invasion,and a high risk of recurrence.MRI is helpful in determining the extent of invasion and neural spread.

Objective:Patient risk-based statistical quality control (SQC) program was designed for 9 specific protein projects using Westgard sigma rules with run length.Methods:The cumulative coefficient of variation of immunoglobulin (Ig)G, IgA, IgM, C3, C4, rheumatoid factor (RF), antistreptolysin O (ASO), transferrin (TRF) and prealbumin (PA) from the laboratory department of Beijing Tongren Hospital between December 2018 to May 2019 were used as the estimated value of imprecision. The mean of the absolute value of the percentage difference of 10 batches in the laboratory, which was derived from the results of participating the external quality assessment (EQA), was used as the estimated value of bias. The National Center for Clinical Laboratories EQA evaluation criteria was used as an allowable total error (TEa), and the sigma value of each project (σ) was calculated. Westgard Sigma rule with run length was used to design appropriate SQC program for each project, including quality control rules, number of control measurements (N) and frequency of quality control.Results:The sigma value was larger than 6 for SQC procedure of IgG, IgA, IgM, C4 and TRF. SQC could be established with the use of 1 3s rule, number of control measurements (N)=2, number of runs (R)=1, and a run length of 1 000 patient samples. Combined with the average daily workload, internal quality control could be conducted once every 10 days for IgG, IgA, IgM and C4, every 50 days for TRF. The σ was 5.86 for C3, SQC program could be established with run length of 450 using 1 3S/2 2S/R 4s rule (N=2, R=1), combined with average daily workload, internal quality control could be conducted every 4.5 days. σ was between 3 and 4 for RF, ASO and PA. With the use of 1 3S/2 2S/R 4s/4 1s/6 X rule (N=6, R=1), SQC program with a run length of 45 and higher frequency internal quality control activities. Conclusion:It is feasible to use Westgard sigma rules with run length for the laboratories design of personalized risk-based SQC procedures, the method is very simple and intuitive. This tool is valued to be recommended to be actively applied by all clinical laboratories.

Objective:An on-line calculator for calculating the frequency of internal quality control is recommended to select quality control procedures and appropriate run lengths for general chemistry in Beijing Tongren Hospital.Methods:The cumulative controlled coefficient of variations of 10 general chemical tests in the laboratory department of Beijing Tongren Hospital for 19 consecutive months were used as the imprecision. The mean value of absolute percentage difference between the quality control results and the target value of 15 batches of 10 tests in the external quality assessment (EQA) general chemistry in 2018 was used to estimate the Bias of each test. Use the allowable range of EQA target value of the National Center for Clinical Laboratories in 2018 to estimate the total allowable error (TEa) of each test. The data were input into the Westgard internal quality control frequency calculator, and 10 different candidate statistical quality control (SQC) procedures and corresponding run lengths were calculated online, including single rule and multiple rule, number of quality control concentration levels (or test projects) ranging from 1 to 4. The SQC program with relatively simple quality control rules and long run length was selected according to the actual situation of the laboratory.Results:The 1 3s, N=3 or 1 3s, N=2 rule could be adopted for ALP and CR, and the corresponding run length was 1000. TBIL and ALT projects can adopt 1 3s, N=3 or 1 3s, N=2 rule and its corresponding run length; UA can use multiple rules 1 3S/2 2S/R 4s/4 1s, N=4 (run length 395) or 1 3S/(2of3) 2S/R 4s/3 1s N=3 (run length 259); CHO, AST and AMY can adopt two multiple rules 1 3S/2 2S/R 4s/4 1s, N=4 or 1 3S/(2of3) 2S/R 4s/3 1s, N=3 and their corresponding run length. GGT project can adopt 1 3S/2 2S/R 4s/4 1S, N=4 rule (run length 50); The run length of 10 candidate quality control rules calculated by LDH was too short, the detection performance should be improved preferentially, and the quality control rules and corresponding run length were not recommended for the time being. Conclusion:The Westgard internal quality control frequency online calculator is easy to operate. Clinical laboratories can use this calculator to select SQC program and appropriate run length. It is recommended that laboratories adjust SQC program according to the current actual situation.