Objective To explore the correlation between serum glycosylated hemoglobin(HbA1c),lym-phocyte activation gene-3(LAG-3)and thyroid nodules in patients with type 2 diabetes mellitus(T2DM).Methods A total of 120 T2DM patients with thyroid nodules admitted to the Third Hospital of Hebei Medi-cal University from July 2021 to July 2022 were included as the study group,and 100 simple T2DM patients(without thyroid nodules)were included as the control group during the same period.According to the patho-logical examination results of thyroid nodules,the study group was grouped into a benign nodule group(85 ca-ses)and a malignant nodule group(35 cases).Enzyme linked immunosorbent assay was applied to detect the serum LAG-3 level of all study subjects.Fully automated glycated hemoglobin analyzer was applied to detect HbA1c level in all study subjects.Spearman method was applied to analyze the correlation between serum HbA1c,LAG-3,and thyroid imaging report and data system(TI-RADS)scores in patients with T2DM and thyroid nodules.Multivariate Logistic regression was applied to analyze the influencing factors of T2DM with thyroid nodules.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of HbA1c and LAG-3 levels in T2DM with thyroid nodules.Results Compared with the control group,the level of HbA1c in the study group was obviously higher(P<0.05),while the level of LAG-3 was obviously lower(P<0.05).Compared with the benign nodule group,the serum LAG-3 level in the malignant nodule group was obviously lower(P<0.05),while the level of LAG-3 was obviously lower(P<0.05).Spearman analysis showed a positive correlation between HbA1c level and TI-RADS score in T2DM patients with thyroid nod-ules(r=0.378,P<0.001),while the serum LAG-3 level was negatively correlated with TI-RADS score(r=-0.472,P<0.001).The results of multivariate Logistic regression analysis showed that HbA1c was a risk factor for the occurrence of thyroid nodules in T2DM patients(P<0.05),and LAG-3 was a protective factor for the occurrence of thyroid nodules in T2DM patients(P<0.05).The combination of HbA1c and LAG-3 in the diagnosis of T2DM with thyroid nodules was superior to their individual diagnosis(Zcombination-HbA1c=2.542,P=0.011;Zcombination-LAG-3=3.098,P=0.002).Conclusion Patients with T2DM combined with thyroid nodules have obviously lower serum LAG-3 level and higher HbA1c level,and the two are related to the malignancy of thyroid nodules.

Objective:To explore the mechanism by which Pien Tze Huang improves liver Kupffer cell damage induced by lipopolysaccharide (LPS) by regulating the expression of miR-155.Methods:LPS induced liver Kupffer cells to establish a cell injury model to simulate septic liver injury. RT-qPCR was used to detect the expression of miR-155 in damaged cells, and RT-qPCR, Western Blot, ELISA and flow cytometry were used to evaluate the inflammatory response and apoptosis of damaged cells. Then we treated LPS-induced Kupffer cells with Pien Tze Huang at different concentrations (0 mg/L, 5 mg/L, 10 mg/L and 15 mg/L), and detected the expression of miR-155 in the cells, the inflammatory response of the cells and Apoptosis rate. MiR-155 was silenced in the cell injury model, and RT-qPCR, Western Blot, ELISA and flow cytometry were used to evaluate the effect of miR-155 on inflammatory response and apoptosis of model cells. Overexpression of miR-155 in damaged cells treated with Pien Tze Huang was used to detect changes in cellular inflammatory response and apoptosis. Data are expressed in the form of mean ± standard deviation, and each group of data is analyzed using t test or one-way analysis of variance.Results:In the LPS-induced liver Kupffer cell injury model, the expression of miR-155 was significantly increased ( P<0.05), the expression levels of pro-inflammatory factors IL-6 and TNF-α were significantly increased, and the anti-inflammatory factor IL-10 was significantly increased. was inhibited ( P<0.05), and the cell apoptosis rate was significantly increased ( P<0.05). After Pien Tze Huang treatment, the expression of miR-155 in damaged liver cells was inhibited ( P<0.05), the levels of cellular inflammatory factors IL-6 and TNF-α were inhibited, and the expression of anti-inflammatory factor IL-10 was promoted ( P<0.05). Inhibit cell apoptosis ( P<0.05). Silencing miR-155 reduced the inflammatory response and apoptosis rate of cells ( P<0.05). Overexpression of miR-155 can reverse the effect of Pien Tze Huang on liver cell injury ( P<0.05). Conclusions:In the model of LPS-induced liver Kupffer cell injury, Pien Tze Huang can inhibite the inflammatory response and apoptosis of cells by inhibiting the expression of miR-155.

Objective:To explore the prevalence and independent associated factors of vascular calcification (VC) in non-dialysis chronic kidney disease (CKD) patients of stage 3-5.Methods:It was a single-center cross-sectional observational study. Non-dialysis stage 3-5 CKD patients ≥18 years old who were admitted to the Department of Nephrology, the First Affiliated Hospital of Sun Yat-sen University from May 1, 2022 to December 31, 2022 with VC evaluation were enrolled. The patients' general information, laboratory examination and imaging data were collected. Coronary artery calcification (CAC), thoracic aorta calcification (TAC), abdominal aorta calcification (AAC), carotid artery calcification and aortic valve calcification (AVC) were evaluated by cardiac-gated electron-beam CT (EBCT) scans, lateral lumbar x-ray, cervical macrovascular ultrasound and echocardiography, respectively. The differences in clinical data and the prevalence of VC at different sites of patients with different CKD stages were compared, and the prevalence of VC at different sites of patients in different age groups [youth group (18-44 years old), middle-aged group (45-64 years old) and elderly group (≥65 years old)] and patients with or without diabetes were compared. Multivariate logistic regression analysis was used to analyse the independent associated factors of VC for different areas.Results:A total of 206 patients aged (51±14) years were included, including 129 (62.6%) males. There were 44 patients with CKD stage 3 (21.4%), 51 patients with CKD stage 4 (24.8%), and 111 patients with CKD stage 5 (53.9%). CKD was caused by chronic glomerulonephritis [104 cases (50.5%)], diabetic kidney damage [35 cases (17.0%)], hypertensive kidney damage [29 cases (14.1%)] and others [38 cases (18.4%)]. Among 206 patients, 131 (63.6%) exhibited cardiovascular calcification, and the prevalence of CAC, TAC, AAC, carotid artery calcification, and AVC was 37.9%, 43.7%, 37.9%, 35.9% and 9.7%, respectively. The overall prevalence of VC in young, middle-aged and elderly patients was 24.6%, 73.6% and 97.4%, respectively. With the increase of age, the prevalence of VC in each site gradually increased, and the increasing trend was statistically significant (all P<0.001). The overall prevalence of VC in CKD patients with diabetes was 92.5% (62/67), and the prevalence of VC at each site in the patients with diabetes was significantly higher than that in the patients without diabetes (all P<0.001). Multivariate logistic regression analysis revealed that age (every 10 years increase, OR=2.51, 95% CI 1.77-3.56, P<0.001), hypertension ( OR=5.88, 95% CI 1.57-22.10, P=0.009), and diabetes ( OR=4.66, 95% CI 2.10-10.35, P<0.001) were independently correlated with CAC; Age (every 10 years increase, OR=6.43, 95% CI 3.64-11.36, P<0.001) and hypertension ( OR=6.09, 95% CI 1.33-27.84, P=0.020) were independently correlated with TAC; Female ( OR=0.23, 95% CI 0.07-0.72, P=0.011), age (every 10 years increase, OR=3.90, 95% CI 2.42-6.29, P<0.001), diabetes ( OR=5.37, 95% CI 2.19-13.19, P<0.001) and serum magnesium ( OR=0.01,95% CI 0-0.35, P=0.014) were independently correlated with AAC. Moreover, age and diabetes were independently correlated with carotid artery calcification, AVC and overall VC Conclusions:The prevalence of VC in non-dialysis CKD patients of stage 3-5 is 63.59%, of which CAC reaches 37.9%, TAC is the most common one (43.7%), while AVC is the least one (9.7%). Age and diabetes are the independent associated factors for VC of all sites except TAC, while hypertension is an independent associated factor for both CAC and TAC.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective:To explore the damage of panretinal photocoagulation (PRP) to the subbasal nerve plexus (SNP) and its related mechanisms by comparing SNP changes in wide-field mosaic between before and after PRP treatment in diabetic patients.Methods:A randomized controlled study was conducted.Fifty-seven patients (114 eyes) with type 2 diabetes mellitus and binocular diabetic retinopathy (DR) stage IV to receive PRP treatment in Shanxi Eye Hospital from April to November 2019 were enrolled.The subjects were randomly divided into horizontal-vertical laser group and vertical-horizontal laser group according to a random number table.Twenty-nine eyes from 29 patients were assigned to the horizontal-vertical laser group with the photocoagulation sequence of temporal-nasal-inferior-superior.Twenty-eight eyes from 28 patients were assigned to the vertical-horizontal laser group with the photocoagulation sequence of inferior-superior-temporal-nasal.The severer eyes of each subject were chosen as the treatment eye and the contralateral eyes were chosen as the control eye.Corneal confocal laser scanning microscopy (CCM) was performed before PRP treatment, 1 week after each photocoagulation, and 1 month after the completion of PRP treatment to collect images of the SNP over an area of 2-3 mm around the whorl-like pattern.Captured images at each time were merged into one image by using the Photoshop CC 2017 image processing software, and then the nerve fiber length (NFL) of whorl-like pattern was measured by Neuron J image analysis software.McGill pain questionnaire was used to investigate the pain of patients after each photocoagulation.The NFL changes of SNP at different time points were compared between different eyes and different photocoagulation sequence groups.The study protocol adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Shanxi Eye Hospital (No.201804b). Written informed consent was obtained from each patient prior to entering the study cohort.Results:After PRP treatment, there were different degrees of neural structure loss of SNP nerve fibers in 11 treatment eyes, but there was no significant change in SNP nerve fibers in the control eyes.There were significant differences in NFL between the treatment eyes and the control eyes at various time points ( Feyes=2.020, P=0.039; Ftime=4.062, P=0.001). In the horizontal-vertical laser group, different degrees of neural structure loss on the photocoagulation side were found in SNP nerve fibers after the first and second photocoagulation.In the vertical-horizontal laser group, different degrees of neural structure loss on the photocoagulation side were found in SNP nerve fibers after the third and fourth photocoagulation.There was no significant difference in NFL of treatment eyes between the two groups ( Fgroup=0.099, P=0.754), but there was a significant difference in NFL at various time points before and after treatment ( Ftime=5.231, P<0.001). There were 9 (9/57) patients who complained of pain after PRP, which occurred at the first time of photocoagulation in 7 of them. Conclusions:SNP damage may occur after PRP in patients with DR, and SNP is prone to be damaged on the photocoagulation side when performing horizontal photocoagulation.

Objective:To study the distribution and drug resistance of Carbapenem-Resistant Organism (CRO) and to analysis the risk factors of CRO 30-day mortality.Methods:A total of 181 patients with CRO infection diagnosed in Department of Hematology, Fujian Medical University Union Hospital from January 2018 to June 2020 were retrospectively investigated. The clinical and laboratory data of the patients were collected, the prognosis of patients diagnosed with CRO infection in day 30 was followed up, and the risk factors of prognosis were analyzed. The clinical significance of Carbapenem-Resistant Enterobacteriaceae (CRE) active screening was further evaluated in the CRE subgroup.Results:Among the total of 181 CRO isolates, 47.2% were CRE, 37.0% were Pseudomonas aeruginosa, and 32.6% were Klebsiella pneumoniae, which were highly resistant to carbapenem and had high MIC value, 76.8% (139/181) of CRO were MIC of imipenem resistance≥16 μg/ml. The main sources of isolates were blood and sputum. The 30-day all-cause mortality rates of patients with CRO or CRE infection were (41.4±3.7) % and (44.7±5.4) %, respectively. The COX multivariate regression analysis showed that the level of procalcitonin >0.2 ng/ml and the MIC value of imipenem resistance ≥ 16 μg/ml were independent risk factors for 30-day mortality of CRO infected patients. The CRE subgroup analysis showed that MIC value of imipenem resistance ≥16 μg/ml were independent risk factors for 30-day mortality of CRE infected patients. The 30-day cumulative survival rate of patients with CRE active screening was higher than the patients without CRE active screening [ (68.0±9.3) % vs (50.0±6.5) %, P=0.21]. Conclusion:The high MIC value of imipenem resistance isolates seriously affects the prognosis of patients with CRO infection in the hematology department, and the mortality rate was high. CRE active screening is expected for early prevention, early diagnosis, and early treatment for high-risk patients.

Objective:To evaluate the clinical efficacy and safety of modified chitosan eye drops on rabbit Candida albicans keratitis model.Methods:Ten healthy female New Zealand rabbits were used to establish the superficial Candida albicans keratitis model by the corneal surface lens method in the right eye.Slit lamp microscopy and corneal scraping and microscopic examination were performed to preliminarily determine whether the keratitis model has been successfully established, the rabbits were then randomly divided into a model group and a modified chitosan group by the random number table method.The successfully established rabbit models which were determined by fungal culture results were retained.Five normal rabbits receiving no intervention served as a normal control group.The experimental eyes in the normal control and modified chitosan groups were treated with modified chitosan eye drops, Six times a day for one week, and subsequently four times a day for one week.No treatment was administered to the model group.The changes of corneal lesions and ocular surfaces were examined by slit lamp microscopy every day.At 1, 7, 14, 21 and 28 days after modeling, the eye condition and corneal clinical scores was assessed by slit lamp microscopy.The corneal conditions in each group was observed for two weeks after drug withdrawal.Results:The corneal scraping and microscopic examination results of eight rabbits models showed that the fungal hyphae and spores were positive.The fungal culture results showed that the separated pathogen was Candida albicans.The success rate of modeling was 80%(8/10). The clinical scores in the model group at 7, 14 and 21 days after modeling were 14.50±0.58, 6.25±0.50 and 2.50±0.58, respectively, and were significantly higher than 7.25±1.26, 2.75±0.50 and 1.25±0.50 in the modified chitosan group (all at P<0.05). In the model group, corneal edema was significantly aggravated, and the central white ulcer area was enlarged within seven days after modeling.Between 7 and 28 days after modeling, the corneal ulcer was gradually healed, while the central corneal scar and neovascularization were remained.The average healing time was (24.5±2.6)days.In the modified chitosan group, the corneal infiltration was significantly alleviated within seven days after modeling, and the fungal hyphae and spores of corneal scraping were negative on the 14th day after modeling.The average healing time in the modified chitosan group was (13.5±1.3)days, which was significantly shorter than that in the the model group (P<0.01). No recurrence of keratitis was observed in the modified chitosan group after two weeks of drug withdrawal.The cure rate was 100%.In the normal control group, the conjunctival hyperemia, corneal edema, and lesions were not observed during topical administration.Conclusion:The treatment with modified chitosan eye drop is effective in a rabbit superficial Candida albicans keratitis model, and have no obvious toxic effects on ocular tissues.

Objective:To estimate the correlation between DR and diabetic corneal nerve damage by comparing changes of corneal sub-basal nerve plexus (SNP) in the whorl-like region in different DR stages.Methods:In this cross-sectional study, 66 eyes of 66 type 2 diabetes patients aged 50-65 years old in Shanxi Eye Hospital from September 2018 to January 2019 were included.The subjects were divided into non-diabetic retinopathy group (NDR), non-proliferative diabetic retinopathy group (NPDR) and proliferative diabetic retinopathy group (PDR) accordingly, the right eyes were enrolled.20 eyes of 20 age and gender matched age-related cataract patients were also included as control group.All the subjects underwent confocal corneal microscopy to observe the morphology of SNP in the whorl-like region and measure the nerve fiber length (NFL) in this area.Covariance analysis using disease course as the covariate was used to analyze the differences of NFL value among groups, and Spearman rank correlation analysis was used to analyze the correlation between NFL value and DR stages.The study protocol was approved by the Ethics Committee of Shanxi Eye Hospital.Written informed consent was obtained from each patient prior to entering the study cohort.Results:The whorl-like region were observed in all the eyes.In the control group, nerve fibers were uniform in thickness, densely distributed with regular course, and most of the tested eyes had intact whorl-like structure.Nerve fibers in different DR groups all showed generally decrease in diameter and density, with increase in tortuosity, accompanied by different degrees of whorl-like structure loss.Eyes in the NDR group and NPDR group mainly showed nerve structure loss in the whorl-like center; while some eyes in the PDR group also showed nerve structure loss in the inferior and temporal of the whorl-like region.The NFL values were (21.08±4.74), (16.47±6.35), (14.95±3.90), and (11.61±3.24)mm/mm 2 in the control group, the NDR group, the NPDR group, and the PDR group, respectively, the overall difference was statistically significant ( F=10.541, P<0.001). The NFL value in the control group was significantly higher than those in the different DR groups, the differences were statistically significant (all at P<0.01). Spearman rank correlation analysis showed that there was a significant negative correlation between NFL value and DR stages ( rs=-0.356, P=0.003). Conclusions:Diabetic SNP damage occurs earlier than DR, and progress gradually with the development of DR; Different stages of DR are accompanied by different degrees of nerve structure loss; The structure loss begins at the whorl-like center and gradually develops to downward and the temporal side.The ophthalmologists should take the condition of ocular surface into account when treating ocular fundus diseases of diabetic patients.

Objective To evaluate the effectiveness of intense pulsed light (IPL) therapy for meibomian gland dysfunction (MGD).Methods A prospective senal cases observational study was designed.Thirty patients with MGD (60 eyes)in the Tianjin Medical University Eye Hospital from October 2017 to April 2018 were enrolled.All the subjects received IPL therapy at baseline,1 week and 3 weeks after the baseline,respectively.Before each treatment and 3 months after treatment,subjective symptoms (ocular surface disease index [OSDI] questionnaire,Standard Patient Evaluation of Eye Dryness [SPEED] questionnaire),palpebral margin score,lipiview ocular surface interferometer lipid layer thickness (LLT) measurement,tear meniscus height (TMH) and noninvasive tear film breakup time (NIBUT) measurement were performed to detect and assess the IPL treatment effect.The safety of the IPL treatment was evaluated through the visual acuity and intraocular pressure.Results The OSDI score,SPEED score and the score of lipid excretion and secretion of meibomian gland before treatment were significantly higher than those of the other three time points (all at P＜0.01).The TMH before treatment was significantly lower than that of the other three time points (all at P＜0.01).No significant differences were obtained on first time NIBUT,blinking times and incomplete blink ratio among different time points (all at P＞0.05).After treatment,the average thickness of tear film lipid layer was slightly increased,and the secretion of tarsal gland was improved.There were no adverse reactions during the treatment and follow-up,no changes in corrected vision,and the intraocular pressure fluctuated within the normal range.Conclusions IPL therapy can alleviate the symptoms and signs of dry eye of MGD patients,and the effect can last for at least 3 months.IPL is an effective and safe method in treatment of MGD.

We have evaluated the plague epidemic situation in the Three Rivers Source Region,Qinghai Province in recent 20 years to provide the basis for revising the plague prevention countermeasures.We have analyzed the time distribution and the plague epidemic situation between animals and human beings during twenty years in the Three Rivers Source Region,Qinghai Province by describing epidemiology.The animal plague in the natural source of Marmot plague was extremely serious in the Three Rivers Source Region during the past 20 years.It mainly distributes in Yushu State and Tanggula County,Germu City and the serious season ran through the whole period of marmot camp ground activities and the peak was between June and August.Human plague epidemic took place between May and October each year and reached its peak between July and September.The peak covered about 41.67％ at most.It mainly endemic distributes in Nangqian and Xinghai Country.During the past 20 years,we have totally found 14 human plague epidemics in the Three Rivers Source Region,among which 48 cases took place and there were deaths of 17 cases.The fatality rate was 35.42％.The lung type was the majority among 48 cases,which startde with the glandular type.During the past 20 years the plague epidemic has been active and the animal plague epidemic broke out continuously in the Three Rivers Source Region,Qinghai Province.The variety of animals and insects infected the plague epidemic was increasing.The human plague epidemics is most serious with high fatality rate,but it is on the decline as a whole.