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Objective: To conduct a comparative analysis of the efficacy, safety, and cytokine changes associated with three distinct dose escalation regimens of allergen-specific immunotherapy (AIT), and to provide valuable insights into the implementation of safer and more effective accelerated immunotherapy in clinical practice. Methods: A prospective study of subcutaneous immunotherapy (SCIT) was conducted at Renmin Hospital of Wuhan University, involving patients with allergic rhinitis visited from 2019 to 2022. Participants were allocated to one of three treatment groups based on their preferences: conventional immunotherapy (CIT, 23 cases), cluster immunotherapy (CLIT, 25 cases), or rush immunotherapy (RIT, 18 cases). The RIT group received a single subcutaneous injection of 150 mg of omalizumab one week before commencing treatment. Subjective evaluation indices, including the Combined Symptom and Medication Score (CSMS), Visual Analogue Scale (VAS), and single symptom score, were recorded alongside objective evaluation indices (e.g., sIgE, tIgE, Th1/2 and Th17 cytokines) and adverse reactions. Assessments were conducted at baseline, and at 1, 7, and 15 weeks after treatment. SPSS 22.0 software was used for data processing and analysis. Results: The study included a total of 66 patients, comprising 37 males and 29 females, who completed the treatment regimen. In all three groups, CSMS and VAS scores showed significant reductions at 1, 7, and 15 weeks post-treatment (all P <0.05). Notably, the RIT group demonstrated a significantly lower VAS score (4.33±0.94) compared to the CIT (9.48±1.37) and CLIT (9.44±1.33) groups at 1 week post-treatment ( P <0.05). Additionally, the RIT group (0.62±0.23) exhibited a lower CSMS score than the CIT (1.54±0.21) and CLIT (1.06±0.22) groups at 15 weeks post-treatment ( P <0.05). Furthermore, at the point of reaching the maintenance dose, the RIT group (0.61±0.20) demonstrated superior improvement in nasal itching symptoms compared to the CIT (1.78±0.38) and CLIT groups (1.56±0.32), with P <0.05. The incidence of local adverse reactions in the RIT group (36/11.76%) was lower than that in the CIT (69/20.00%) and CLIT groups (62/16.53%), with P <0.05. Notably, none of the three groups reported grade 3/4 systemic adverse reactions, and there was no statistically significant difference in systemic adverse reactions among the three groups. Following treatment, IL-4, IL-5, IL-6, IL-17, sIgE, sIgE/tIgE, and Eos% exhibited varying degrees of decrease in all three groups, whereas IL-10, TNF, and IFN-γ did not show significant changes. Conclusions: All three distinct dose escalation regimens of SCIT demonstrated substantial clinical efficacy. Of note, the approach of combining a single injection of omalizumab with RIT significantly improved early-stage efficacy and exhibited the advantages of safety, effectiveness, and convenience, establishing it as a reliable immunotherapy method.

Dry eye is a common ocular surface disease worldwide that affects the patients' visual quality and life quality. Correctly distinguishing its etiology, severity and subtypes is the basis for precise diagnosis and effective treatment. This article summarizes the challenges and bottlenecks in the development of dry eye precise diagnosis, and discusses the current situation and development trend of dry eye diagnosis from traditional evaluation methods to novel diagnostic techniques, aiming to provide reference and guidance for promotion of clinical precise diagnosis of dry eye.

Objective: The study aims to investigate the characteristic baseline information about genetic lineages, drug-resistance genes, virulence genes and evolutionary relationships of food-borne Listeria monocytogenes (Lm) isolates from Nanshan district of Shenzhen. Methods: The whole genomes of 46 Lm isolates during 2009-2019 were extracted and sequenced (Illumina PE-150, 100×). The CLC Genomics Workbench 12.0 was used to assemble and align Lm genomes, analyze their housekeeping genes, drug-resistance genes and virulence genes, and construct a k-mer phylogenetic tree. Results: After assembly, all genomes satisfied analytical conditions (contigs N50>20 kb). The medians of GC content, gene count and gene size were 38.3%, 5 960 and 2 952 608 bp, respectively. Based on the Lm genomic reference database, the local k-mer phylogenetic tree had 14 clusters of which the genetic distance was wide. The 46 Lm isolates were classified as Lineage 1 (21), Lineage 2 (23) and Lineage 3 (2). The most common ST type of Lineage 1 was ST87, followed by ST3, ST59, ST224 and ST429, whereas the major ST types of Lineage 2 included ST8 and ST9, the rest being ST121, ST155, ST199, ST204 and ST321. However, Lineage 3 only had ST299. The part of Lm strains carried five drug-resistance genes, such as fosX (17), tetM (6), dfrG (4), catB3 (1) and mefA (1). Furthermore, all strains possessed nine virulence genes, including flaA, iap, actA, hly, mpl, prfA, plcA, plcB and inlB. Nevertheless, six isolates and three of them respectively carried the mutant inlA and inlJ, and other two isolates lacked inlC. Conclusion: The food-borne Lm isolates from Nanshan district of Shenzhen presented genetic and evolutionary diversity. Noted that the drug-resistant strains, which also owned abundant virulence genes with specific functions, could lead to serious infections, particularly those isolates from raw poultry and Flammulina velutipes. It was implied that the local region was at risk due to Listeriosis by food. This study offered reference for prevention, control and treatment of Lm infection to the Greater Bay Area.

Objective: To explore the expression and significance in regulating immune balance of programmed cell death protein 1 (PD-1) and its ligands PD-L1, PD-L2 in allergic rhinitis (AR). Methods: Eighty-two patients who received outpatient treatment due to high nasal reaction symptoms or were hospitalized due to nasal septum deviation and underwent nasal septum correction surgery in Department of Otorhinolaryngology Head and Neck Surgery of Renmin Hospital of Wuhan University from May 2018 to May 2019 were enrolled, including 42 males and 40 females, with the age ranging from 14 to 38 years old. Blood, inferior turbinate nasal mucosal tissue and relevant clinical data were collected. Patients were divided into AR group and control group due to clinical manifestation, skin prick test and detection of specific IgE (sIgE) in serum. Immunohistochemistry was used to detect the expression of PD-1 and its ligands in nasal mucosa of the two groups. Flow cytometry was used to detect the proportions of PD-1(+)CD4(+)T cells, PD-L1(+) myeloid dendritic cells (mDCs), PD-L2(+)mDCs and Th2 cells in peripheral blood of the two groups. The expression levels of total IgE, sPD-1, sPD-L1 and sPD-L2 in serum of the two groups were detected by ELISA. The measurement data of normal distribution or normal distribution after the logarithm conversion to Ln were compared by t test. Pearson correlation or Spearman correlation was used to analyze the correlation among the indicators. P< 0.05 was considered statistically significant. Results: The expression of PD-1 and its ligands on the surface of immune cells in the nasal mucosa of the AR group was significantly higher than that of the control group. The ratio of PD-1(+)CD4(+)T cells, PD-L1(+)mDCs and Th2 cells in peripheral blood of AR group was significantly higher than that of the control group ((15.24±6.45)% vs (8.71±5.33)%, (8.79±2.01)% vs (5.74±2.90)%, (7.89±1.95)% vs (2.52±1.34)%, all P< 0.05). There was no significant difference in the ratio of PD-L2(+)mDCs between the two groups. Correlation analysis found that the proportion of PD-1(+)CD4(+) T cells was positively correlated with the Visual Analogue Scale (VAS) score of AR, total IgE concentration and the serum sIgE concentration ( r value was 0.501, 0.541, 0.608, respectively, all P< 0.05). The proportion of PD-L1(+)mDCs was positively correlated with the VAS score of AR and the serum sIgE concentration ( r value was 0.604, 0.563, respectively, all P< 0.05). The proportion of Th2 cells in peripheral blood was positively correlated with the proportion of PD-L1(+)mDCs and PD-1(+)CD4(+)T cells ( r value was 0.538, 0.623, respectively, all P< 0.05). Serum total IgE, sPD-1 and sPD-L1 in the AR group were significantly higher than those in the control group ((6.34±1.38) ng/ml vs (4.89±1.10) ng/ml, (4.40±1.01) pg/ml vs (3.79±1.21) pg/ml, (3.88±0.25) pg/ml vs (3.57±0.23) pg/ml, all P< 0.05), and there was no significant difference in sPD-L2 levels between the two groups. Correlation analysis showed that sPD-L1 was positively correlated with total IgE and sIgE concentration ( r values was 0.32, 0.45, respectively, all P< 0.05). Conclusions: PD-1 and PD-L1 are highly expressed on the surface of immune cells in peripheral blood and nasal mucosa of AR patients, and sPD-1 and sPD-L1 expression levels in peripheral blood of AR patients are increased. The PD-1/PD-L1 signaling pathway promote AR inflammatory response by inducing Th2 type immune response.

Objective: To understand the characteristics of HIV/AIDS epidemic in Guangxi Zhuang Autonomous Region (Guangxi) with a purpose to accurately provide scientific basis for prevention and control measures, 2010-2017. Methods: Data were retrieved from case reporting cards of Guangxi during 2010 to 2017 through National HIV/AIDS Comprehensive Response Information Management System. Data was analyzed using epidemiological methods such number of cases, proportion and rate. χ (2) test was used for statistical analysis. Results: The HIV positive rate was 12.53 per ten thousand (85 182/67 959 000) in Guangxi during 2010 to 2017. The number of newly diagnosed HIV/AIDS cases and the number of death yearly respectively increased by 22.34 % (2 602/11 648) and 32.83 % (952/2 900) in 2011 compared with 2010, and both showed a six-year continuous downward trend (the number of newly diagnosed cases respectively 12 229 cases, 10 877 cases, 9 460 cases, 9 190 cases, 8 848 cases, 8 680 cases, and the number of death respectively 3 888 cases, 3 316 cases, 2 914 cases, 2 717 cases, 2 595 cases, 2 600 cases) from 2012 to 2017. But proportion of late discovery remained above 50.00 % (50.53 % -57.06 % ) for eight-years continuously. The ratio of male and female was 2.47 ∶ 1 (60 639/24 543). The ratio of males and females aged 50 and over was 2.71∶1 (28 654/10 557). Proportion of the cases in 25-49 years old group and 50 years old group accounting for 47.40 % (40 377/85 182) and 46.03 % (39 211/85 182) respectively. The occupation was farmers accounting for 68.40 % (58 262/85 182), housekeeping, housework and unemployment accounting for 11.21 % (9 546/85 182), student accounting for 0.86 % (729/85 182). Heterosexual transmission accounted for 90.60 % (77 171/85 182, homosexual transmission accounted for 3.13 % (2 669/85 182), injection drug use transmission accounted for 4.60 % (3 924/85 182) and mother-to-child transmission accounted for 0.73 % (619/85 182). Conclusions: The number of newly diagnosed cases and the number of death yearly showed a continuous downtrend for six-years from 2012 to 2017. However, proportion of late discovery remained above 50.00 % for eight-years. The major route of infection was heterosexual transmission. With the change of HIV/AIDS newly epidemic mode in Guangxi, there are many new challenges for HIV/AIDS prevention and control work. Strategy of targeted intervention modes should be innovated for a new breakthrough.

Nowadays, diabetes is quickly emerging as one of the biggest health-related catastrophes over the world. Its impact on people's quality of life has been gradually taken seriously. In the past few years, the connection linking dry eye to diabetes has been substantially confirmed by a series of studies. However, many areas remain uncertain due to the complex and diverse pathogeneses of diabetes related dry eye syndrome. Furthermore, the slow progression of dry eye symptoms easily conceals its connection with diabetes, which brings great challenges to timely diagnosis and effective interventions. This article aims at improving the clinical understanding of this kind of disease and standardizing its diagnosis and treatment by outlining the correlation between diabetes and dry eye. (Chin J Ophthalmol, 2017, 53: 645-647) .

Objective: To analyze the epidemiological characteristics and spatial distribution of human brucellosis in Fujian province during 2011-2016, and provide evidence for the prevention and control of the disease. Methods: The surveillance data of human brucellosis in Fujian during 2011-2016 was analyzed with software R 3.3.1, ArcGIS 10.3.1, GeoDa 1.8.8 and SaTScan 9.4.3. Results: During 2011-2016, a total of 319 human brucellosis cases were reported, the incidence increased year by year ( F =11.838, P =0.026) with the annual incidence of 0.14/100 000. The male to female rate ratio of the incidence was 2.50 ∶ 1. Farmers and herdsmen accounted for 57.37 % . The incidence was 0.40/100 000 in Zhangzhou and 0.32/100 000 in Nanping, which were higher than other areas. The number of affected counties (district) increased from 12 in 2011 to 28 in 2016, showing a significant increase ( F =13.447, P =0.021). The Moran's I of brucellosis in Fujian between January 2011 and December 2016 was 0.045, indicating the presence of a high value or low value clustering areas. Local spatial autocorrelation analysis showed that, high-high clustering area (hot spots) were distributed in Zhangpu, Longhai, Longwen, etc , while high-low clustering areas were distributed in Nan'an and Jiaocheng, etc . Temporal scanning showed that there were three clustering areas in areas with high incidence, the most possible clustering, occurring during January 1, 2013- December 31,2015, covered 6 counties, including Yunxiao, Pinghe, Longhai, etc , and Zhangpu was the center, ( RR =7.96, LLR =92.62, P <0.001). Conclusions: The epidemic of human brucellosis in Fujian is becoming serious, and has spread to general population and non-epidemic areas. It is necessary to strengthen the prevention and control of human brucellosis in areas at high risk.

Objective: To explore the role of σ1 receptor (σ1R) in the clinical prognosis of cervical cancer,and provide a theoretical basis for σ1R targeted molecular therapy through observing the inhibition of synthetic σ1R-specific ligand compounds on the growth of cervical cancer cells. Methods: (1) Immunohistochemical or immunocytochemistry staining were respectively used to detect the expression and localization of σ1R protein. (2) The Cancer Genome Atlas (TCGA) data set was used to validate our results. (3) Two series of 4 novel σ1R ligand compounds were synthesized by altering the N-terminal substituents on the piperidine ring of the prezamicol analogue, named as 14a, 14e, 15c and 15f. Methyl thiazolyl-tetrazolium (MTT) assay was detect the anti-proliferative effect of the four compounds on HeLa and SiHa cells. Compound 14a with potent inhibitory activity and the highest specificity of σ1R was selected for further experiments. Scratch test was observed the migration effect of compound 14a on HeLa and SiHa cells. Flow cytometry was determined cell cycles and apoptosis. Results: (1) Immunostaining of σ1R protein was located in the cytoplasm and nucleus of cervical epithelium. The expression of cervical squamous cell carcinoma (SCC) was significantly higher than those of high-grade squamous intraepithelial lesion (HSIL) or normal cervical tissues. There was no significant difference in the expression of σ1R between HSIL and normal cervical tissues. σ1R expression in cervical adenocarcinoma (AC) was higher than that in SCC ( P= 0.020). The nuclear expression rate of σ1R in AC (10/18) was higher than that of SCC (27.1%, 19/70; P= 0.024). The median overall survival (MOS) of σ1R-positive SCC patients was lower than that of σ1R-negative patients [(45.8±3.1) vs (51.7±2.9) months, P= 0.045]. MOS of the patients with σ1R nuclear positive SCC was lower than that of non-nuclear staining [(38.9±3.8) vs (48.7±2.1) months, P= 0.022]. MOS of the patients with σ1R nuclear positive AC was lower than that of non-nuclear staining [(35.0±6.3) vs (44.2±4.2) months, P= 0.034]. (2) Analysis of TCGA data showed that σ1R expression of in SCC was correlated with age ( P= 0.005). σ1R expression in AC was significantly associated with advanced stage, lymphnode metastasis and vascular invasion (all P< 0.05). MOS of AC patients with σ1R overexpression was significantly lower than that of the patients with low expression ( P= 0.034). There was no significant difference in the MOS of different expression of σ1R mRNA in SCC patients( P= 0.930). (3) MTT assay showed that these four compounds could suppressed the growth of HeLa and SiHa cells in time- and dose-dependent manner. The growth inhibition rates of HeLa and SiHa cells at 48 hours treated by combination of different concentrations of nedaplatin (NDP) with compound 14a (6 μmol/L) were significantly higher than those treated by NDP alone. Compound 14a (30 μmol/L) significantly inhibited the migration (both P< 0.01) and induced the apoptosis of HeLa or SiHa cells (both P< 0.01). Conclusions: σ1R is over-expressed in cervical cancer and HSIL. σ1R nuclear expression is an important marker of AC. σ1R over-expression, especially σ1R nuclear expression is associated with the poor prognosis of cervical cancer. Our study is mostly consistent with cervical cancer data of TCGA. These results suggest that the novel synthetic prezamicol analogues 14a for σ1R could inhibit the growth of cervical cancer cells and cell migration through inducing apoptosis and arresting cell cycle in G(0)/G(1) period, enhance NDP-induced cytotoxicity.

Objective: To discuss the relationship between lingual tonsil hypertrophy and laryngopharyngeal reflux. Methods: Ninety-two patients who received throat surgery in Nanfang Hospital between October 2015 and October 2016 were enrolled. Twenty-six healthy volunteers were recruited as normal controls. All participants were assessed with the reflux finding score(RFS) and the size of lingual tonsils were evaluated using a clinical grading system proposed by Friedman under electronic laryngoscope. The score of reflux symptom index(RSI), personal history and medical history were gathered. Biopsy specimens of lingual tonsils were taken from all participants for the immunohistochemical stain of pepsin.SPSS 19.0 software was used for statistical analysis. Results: There were 46.2% (12/26) pepsin-positive and 53.8% (14/26) pepsin-negative volunteers in normal controls. There were 87.0% (80/92) pepsin-positive and 13.0% (12/92) pepsin-negative patients in study group. The severity of lingual tonsil hypertrophy and expression intensity of pepsin in patients were significantly higher in volunteers ( Z =-3.636, Z =-5.273, P <0.01). The severity of lingual tonsil hypertrophy was positively associated with the pepsin level in patients ( r =0.556, P <0.01). The patients with pepsin-positive expression showed significant correlation between lingual tonsil hypertrophy and the positive rate of RSI and RFS ( r =0.258, r =0.225, P <0.05). Analysis of correlated factors indicated that lingual tonsil hypertrophy was associated with smoking (χ(2)=8.502, P <0.05). Conclusions: The expression of pepsin can be detected in lingual tonsil tissues. The lingual tonsil hypertrophy is closely related to laryngopharyngeal reflux.

Objective: To compare the differences of the sites of airway obstruction in OSAHS patients between awake and sleep state by using the VOTE classification system. Method: Forty OSAHS patients diagnosed by PSG underwent awake Müller's maneuver and drug-induced sleep endoscopy (DISE). Video and compare the observation. Its findings were described using the VOTE classification system which include the following features: level, degree and configuration of obstruction. Associations were analyzed between different degrees of obstruction, BMI, AHI, minimal SaO₂ and average SaO₂. Result: Our patients had 52.5% complete velum collapse and 30.0% complete oropharyngeal lateral wall collapse in awake Müller's maneuver. In DISE, airway closure of 95.0% cases related to velum occurred collapse in concentric configuration, and 90.0% cases showed completely obstructive. We found that 60.0% complete oropharyngeal lateral wall collapse and 17.5% complete tongue base collapse. There was a significant difference in the VOTE scores between DISE and awake Müller's maneuver, and the VOTE scores of DISE were higher in all levels ( P <0.05). No association was found between degrees of obstruction, AHI, BMI, minimal SaO2 and average SaO₂ in Müller's maneuver ( P >0.05). Complete velum collapse was just significantly associated with AHI and minimal SaO₂ in DISE ( P <0.05). Conclusion: The VOTE scores of DISE were higher than awake Müller's maneuver, reflected by more obstructive levels and severe degree. The difference between different degrees of obstruction, BMI, AHI, minimal SaO₂ and average SaO₂ was not significant., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To understand HIV-1 subtype characteristics and transmission clusters in elderly male clients and female sex workers (FSWs) of low-cost commercial sex venues in Guangxi Zhuang Autonomous Region, China. Methods: A cross sectional survey was conducted in FSWs and elderly male clients (≥50 years) of low-cost commercial sex venues in 4 cities and 9 counties in Guangxi Zhuang Autonomous Region by convenient sampling in 2012. The blood sample was collected from each case for HIV-1 antibody detection. The pol gene fragments were amplified and sequenced from viral RNA template extracted from plasma samples. The phylogenetic tree was constructed and the subtypes were identified. Results: A total of 4 048 elderly male clients and 784 FSWs were surveyed, and 116 HIV-1 infections were detected, the positive rate was 2.5% (103/4 048) in the clients and 1.7% (13/784) in FSWs. The gene amplification and sequencing of HIV-1 detected in 84 blood samples indicated that 53 pol gene sequences were successfully determined (48 blood samples from elderly male clients and 5 blood samples from FSWs). Among 53 pol sequences, 48(90.6% ), 4(7.5% ), and 1(1.9% ) sequences were identified as CRF01&#95;AE, CRF08&#95;BC, and CRF07&#95;BC, respectively. Two transmission clusters were identified among CRF01&#95;AE, including 4 sub-clusters. One transmission cluster was identified among CRF08&#95;BC. The transmission cluster or sub-cluster were from the infected individuals at same low-cost commercial sex venue, or different low-cost commercial sex venues in the same town, or same place, or adjacent villages and towns. Conclusions: CRF01&#95;AE was the predominant HIV-1 subtype among elderly male clients and FSWs of low-cost commercial sex venues in Guangxi Zhuang Autonomous Region, circulating in same venue or adjacent villages and towns. The HIV-1 positive male clients and FSWs might play an important role in the spread of the strains.

Objective: To explore the relationship between the liver fibrosis criteria and TCM Syndrome, type in the patients suffering from non-alcoholic fatty liver., Methods: Seventy-nine patients with non-alcoholic fatty liver diagnosed by B ultrasonography were classified by TCM Syndrome Differentiation and their liver fibrosis criteria was determined and compared with those of the health subjects as control., Results: Levels of procollagen III (PCIII), hyaluronic acid (HA), collagen IV (CIV) and laminin (LN) in the fatty liver group were significantly higher than those in the control group (P < 0.05, P < 0.01). In respect to the TCM Syndrome-types, PCIII, CIV and LN in patients of Phlegm-stasis combined type were significantly higher than those in patients of other two Syndrome-types (P < 0.05, P < 0.01), while HA was insignificantly different (P > 0.05)., Conclusion: There was trend of liver fibrosis in fatty liver patients. It was indicated that the Phlegm-stasis combined Syndrome-type possibly was the main TCM pathologic factor of the increasing of fibrosis criteria for non-alcoholic fatty liver.

Objective: To investigate the effects of TNP-470 on human salivary adenoid cystic carcinoma cell line ACC M in vitro., Methods: Cell proliferation was assessed by MTT assays and dye exclusion counting. Morphological changes of apoptosis were observed with fluorescent microscope. DNA ladder, apoptosis rate and cell cycle were examined by DNA agarose gel electronphores and fluorescence flow cytometry (FCM), respectively., Results: The 50% inhibitory concentrations (IC50) of TNP-470 on ACC-M cells proliferation by MTT assays and dye exclusion counting were 40.68microg/ml and 46.38microg/ml. Apoptosis were observed by fluorescent microscope. DNA electrophoresis for the cells treated with TNP-470 showed brighter DNA ladder; Sub-G1 peak and G2/M arrest were also determined by FCM (P<0.01)., Conclusion: TNP-470 has the effect of inducing apoptosis in ACC-M cells in vitro, which may be one of its antitumor mechanisms.

Serum adenosine deaminase (ADA) of 74 liver cirrhosis patients and 100 healthy subjects as control were examined with improved Martinek microassay and peripheral T lymphocyte subsets of 38 liver cirrhosis patients and 60 healthy subjects studied by indirect immunofluorescence assay (IFA) for exploring the relationship between them and syndrome types of TCM. The result showed that level of ADA of liver cirrhosis patients was higher than that of control (P < 0.01) and increased in following order: the type of Liver-energy Depression and Spleen Deficiency, that of Heat-Stagnation and Blood Stasis and that of Yin-Deficiency and Microvessel Obstruction. The difference of serum ADA among the types were significant (P < 0.01). The result also showed that OKT8 of liver cirrhosis patients was higher, the ratio of OKT4/OKT8 was lower than the healthy subjects (P < 0.05-0.01), but the difference among the types were not significant (P > 0.05). Serum ADA seemed to be one of the reference indexes in differentiating syndrome types of TCM, determining the patient's condition and prognosis.