Objective To investigate the causal relationship between circadian rhythm disruption and inflammatory bowel disease(IBD)and the mediating effect of gut microbiota based on Mendelian randomization(MR).Methods Summary statistics of Genome-wide Association Study(GWAS)for circadian rhythm disruption(n=205 527)and IBD(n=214 053)were obtained from IEU OpenGWAS database.Summary statistics of GWAS for the gut microbiota were obtained from the MiBioGen database(n=18 340).Two-sample MR analysis was used to estimate the genetic correlation and causality between circadian rhythm disruption and IBD,and the mediating effect of the gut microbiota was analyzed by two-step MR analysis.Results There was a suggestive causal relationship between circadian rhythm disruption and IBD(odds ratio=1.255,P＜0.05).Rikenellaceae id.967 played a mediating role in the causal chain between them(the mediating effect was-0.028 740).Sensitivity analysis confirmed that the results were not interfered by level pleiotropy and heterogeneity.Conclusion There is a genetic correlation between circadian rhythm disruption and IBD,and gut microbiota may play a mediating role between them.

Objective To establish a mouse model of bronchiectasis with acute infection and evaluate the immunogenicity and protective effect of a self-assembling Pseudomonas aeruginosa(PA)nanoparticle vaccine rePO-FN based on fusion of PcrV-OprI(rePO)protein with self-assembling ferritin(Ferritin).Methods ① SPF-grade female C57BL/6 mice(aged 6～8 weeks,weighing 18～20 g)were randomly allocated into normal saline group,and low-,medium-and high-dose elastase groups(n=6).A mouse model of bronchiectasis was established via intratracheal instillation of different doses of elastase(30 μL of normal saline containing 0.65,1.30 and 2.60 IU elastase)for 3 consecutive days.At 14 and 21 d after modeling,ELISA and HE staining were performed respectively to detect the concentration of IL-6 and to observe pathological changes in lung tissue in order to confirm the modeling.② A recombinant plasmid encoding the gene of fusion protein rePO-FN was constructed and expressed in E.coli.The target protein was purified via affinity chromatography and renatured to obtain the desired protein.The physicochemical properties of the rePO-FN protein were characterized using SDS-PAGE protein gel electrophoresis,dynamic light scattering,molecular sieve chromatography,and transmission electron microscopy.③ C57BL/6J mice were randomly divided into PBS group,rePO group,rePO-FN group,and Ferritin group(n=10).The mice in the above groups were immunized intramuscularly with 100 μL PBS buffer alone or containing 10 μg of corresponding proteins on days 0,7,and 14.ELISA was used to measure the specific antibodies in serum.In 7 d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the PBS,rePO,and rePO-FN groups.After establishing a bronchiectasis model by intratracheal instillation of 2.60 IU of elastase in C57BL/6J mice as described above,the mice were randomly divided into bronchiectasis PBS group,bronchiectasis rePO group,and bronchiectasis rePO-FN group(n=10).Immunization was conducted at the same dose and procedure as described above,in 21 d after bronchiectasis modeling.At the 7th d after the final immunization,an acute PA infection model was used to compare the survival rates and bacterial colonization among the groups.Results ①Repeated intratracheal instillation of elastase significantly increased the concentration of IL-6 in the lung tissue when compared to the content of the normal saline group(P＜0.05).Pathological observations revealed varying degrees of bronchial wall destruction,alveolar fusion,edema,neutrophil infiltration,and hemorrhage,with the severity increasing with elastase dose,which confirming successful establishment of the mouse model of bronchiectasis.② Well-dispersed rePO-FN nanoparticles were successfully prepared,with an average particle size of 91.28 nm,a Zeta potential of approximately-6.5 mV,and a polydispersity index(PDI)of 0.306.Molecular sieve chromatography determined the elution volume of rePO-FN protein to be 8.80 mL,corresponding to a molecular weight of approximately 1 400 kDa.③ Under acute PA XN-1 strain infection,the survival rate of the rePO-FN immunization group and the bronchiectasis rePO-FN immunization group were significantly higher than that of the PBS control group(P＜0.05).Additionally,bacterial colonization in the lung tissues was significantly lower in the rePO-FN immune group and the bronchiectasis rePO-FN immune group under acute PA XN-1 strain infection than that in the rePO group and the bronchiectasis rePO group(P＜0.05).Conclusion Our vaccine rePO-FN can effectively trigger a strong humoral immune response and provide significant protection against PA infection in a mouse bronchiectasis model.

Objective:To investigate the clinical outcomes of sublingual gland flap in the repair of postoperative jaw defects because of chronic phosphorous osteomyelitis(PNJ)and medication-related osteonecrosis of the jaw(MRONT).Methods:3 patients with PNJ and 2 with MRONJ were treated by sublingual gland flap in the repair of the postoperative jaw defet.The treatment effects were evalua-ted by clinical obseration.Results:In the 5 patients the wound healed well within 2 weeks postoperatively,with no infection and with normal sublingual gland function after surgery.Conclusion:The use of sublingual gland flap is an effective and feasible method for re-pairing local defects in the mandibles after surgery for chronic PNJ and MRONJ.

Objective:To investigate the anatomy of rectus femoris muscle flap and the anterolateral thigh muscle flap and their clinical application in reconstruction of large soft tissue defects after the removal of oral malignant tumour.Methods:From December 2006 to June 2009, 8 specimens of Chinese adult cadavers fixed in 10% formaldehyde were dissected to perform anatomy of anterolateral thigh region at the School of Basic Medical Sciences, Kunming Medical University. Anatomical images were analysed using Image-Pro Plus 6.0. Then, a retrospective study was performed on 19 patients who had postoperative defects after oral malignant tumour surgery and the defects were reconstructed with the rectus femoris muscle flap and the anterolateral thigh muscle flap from March 2020 to July 2022 at the Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital, Kunming Medical University. The postoperative defects of the 19 patients ranged from 3.0 cm×6.0 cm to 5.0 cm×10.0 cm. Ten rectus femoris muscle flaps, 8 anterolateral thigh muscle flaps and 1 combined rectus femoris muscle flap and anterolateral thigh muscle flap were used. The muscular flaps sized from 4.0 cm × 8.0 cm to 6.0 cm × 11.0 cm. Regular postoperative outpatient follow-ups were conducted.Results:The lengths of vessels of the harvested rectus femoris muscle flap and anterolateral thigh muscle flap were 63.4 mm± 12.9 mm and 112.5 mm± 19.6 mm, respectively. The starting outer diameters of the lateral circumflex thigh artery, the oblique branch of the lateral circumflex thigh artery and the descending branch of the lateral circumflex thigh artery were 2.92 mm±0.72 mm, 1.88 mm±0.23 mm and 2.29 mm±0.43 mm, respectively. Postoperative follow-up lasted for 7 to 32 months, with 17.5 months in average. Seventeen flaps were completely survived and the rectus femoris muscle flap was completely mucosalised 5 weeks after surgery. However, 2 rectus femoris muscle flaps had necrosis of which one was changed to a tongue flap reconstruction and the other encountered flap necrosis during postoperative radiotherapy and healed after debridement and dressing changes. There was no postoperative complication in the donor sites. Other than the 2 patients, all other 17 patients had satisfactory clinical outcomes.Conclusion:Both of the starting outer diameters and length of vessels of the femoris muscle flap and the anterolateral thigh muscle flap meet the requirements for reconstruction of maxillofacial defects, and both muscular flaps are simple to prepare, in good reconstructive results with few complication, as well as an excellent outcome. They are feasible approaches for reconstruction of large soft tissue defects left after the removal of an oral malignant tumour.

The influence of β-cell function on cardiovascular autonomic neuropathy (CAN), an important diabetes-related complication, is still unclear. In this study, we aimed to investigate the association between residual β-cell function and CAN in patients newly diagnosed with type 2 diabetes. We enrolled 90 newly-diagnosed type 2 diabetic patients and 37 participants with normal glucose tolerance as controls. The patients were divided into a CAN+ group (diabetic patients with CAN, n = 20) and a CAN- group (diabetic patients without CAN, n = 70) according to the standard Ewing battery of tests. Fasting and postprandial plasma glucose, insulin, and C-peptide were measured. Homeostasis model assessment-beta cells (HOMA-B) and HOMA-insulin resistance (IR) were calculated. The prevalence of CAN in this population was 22.2%. Compared with the CAN- group, the CAN+ group had significantly lower fasting plasma insulin (6.60 ± 4.39 vs 10.45 ± 7.82 μ/L, P = 0.029), fasting C-peptide (0.51 ± 0.20 vs 0.82 ± 0.51 nmol/L, P = 0.004), and HOMA-B (21.44 ± 17.06 vs 44.17 ± 38.49, P = 0.002). Fasting C-peptide was correlated with the Valsalva ratio (r = 0.24, P = 0.043) and the 30:15 test (r = 0.26, P = 0.023). Further analysis showed that fasting C-peptide (OR: 0.041, 95% CI 0.003-0.501, P = 0.012) and HOMA-B (OR: 0.965, 95% CI 0.934-0.996, P = 0.028) were independently associated with cardiovascular autonomic nerve function in this population. The patients with fasting C-peptide values < 0.67 nmol/L were more likely to have CAN than those with C-peptide levels ≥0.67 nmol/L (OR: 6.00, 95% CI 1.815-19.830, P = 0.003). A high prevalence of CAN was found in patients with newly-diagnosed type 2 diabetes. Decreased β-cell function was closely associated with CAN in this population.
Adult ; Asian Continental Ancestry Group ; Blood Glucose ; analysis ; Diabetes Mellitus, Type 2 ; complications ; metabolism ; Diabetic Neuropathies ; etiology ; Fasting ; physiology ; Female ; Glucose ; metabolism ; Humans ; Insulin ; metabolism ; Insulin Resistance ; physiology ; Insulin-Secreting Cells ; metabolism ; Male ; Middle Aged

Objective To explore the value of MR T2 mapping imaging in evaluation of the effection of Zhitong-Jiangu recipes in treatment of cartilage injury in osteoarthritis.Methods The models of osteoarthritis in the knee of New Zealand white rabbits were made with intra-articular injection of papain.Totally 48 New Zealand white rabbits were randomly divided into normal control group,model control group,glucosamine hydrochloride treatment group and Zhitong-Jiangu recipes treatment group.MR T2 mapping was performed on the knee and the content of MMP-1 in articular cartilage was analyzed with immunohistochemistry 4 weeks after treatment.The differences of T2 value and MMP-1 content of articular cartilage among the four groups were compared.The correlation among the different intervention methods,MMP-1 content of articular cartilage and the T2 value of articular cartilage were analyzed.Results T2 value of articular cartilage in the model control group was significantly higher than that in the other three groups (all P＜0.01),and there was no significant difference of T2 value among the other three groups.The MMP-1 content of articular cartilage in glucosamine hydrochloride treatment group and Zhitong-Jiangu recipes treatment group was lower than that in model control group (both P＜0.05),and was higher than that in normal control group (both P＜0.05).There was no significant difference between the two groups.The relationship between MMP-1 content and T2 value of articular cartilage was nonlinear.With the increase of MMP-1 content,T2 value first increased slowly and then increased rapidly (P＜0.05).Conclusion MR T2 mapping imaging is helpful to evaluating the efficacy of Zhitong-Jiangu recipes in treatment of cartilage injury in osteoarthritis in rabbit models.The relationship between MMP-1 content and T2 value of articular cartilage may be nonlinear.

AIM:TodetecthemoglobinA1c(HbA1c)andparametersofbloodglucosefluctuationinChinesenewlydiag-nosed type 2 diabetes mellitus (T2DM) patients, and further to specify the factors that were related to mean blood glucose (MBG) in this population.METHODS:Newly diagnosed T2DM patients (n=90) from 4 hospitals in Guangdong province were enrolled, and subjected to 3 d continuous glucose monitoring (CGM) after testing for HbA1c and other laboratory tests.Blood glucose data collected during CGM were used to calculate MBG and parameters of blood glucose fluctuation.RESULTS: Correlation analysis revealed that MBG was significantly related to all parameters of blood glucose fluctuation, HbA1c, fast plasma glucose ( FPG) and 2 h postprandial glucose (P<0.01), but not to sex, age or blood lipid profile.Further analysis utilizing step-wise general linear model showed that HbA1c, absolute means of daily difference ( MODD) , difference between maximal and minimal glucose ( DMMG) and FPG had the strongest relation to MBG.CONCLUSION: Factors affecting MBG of the newly diagnosed T2DMpatients in our country include HbA1c, FPG, DMMG and MODD, and thus it may be prone to misleading results that only HbA1c is applied to estimate MBG in this population.

OBJECTIVETo evaluated the manganese (Mn), cobalt (Co) and molybdenum (Mo) levels in blood and urine among general population in China, and thereby to analyze their prevalent features.

METHODSFrom 2009 to 2010, a total of 18 120 subjects of general population aged 6-60 years were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and their blood and urine samples were also collected.Inductive coupled plasma mass spectrometry (ICP-MS) was applied to test the Mn, Co and Mo levels of blood and urine samples, and the Mn, Co, Mo distribution in blood and urine among groups of population in different ages and genders were then analyzed.

RESULTSAmong general population in China, the geometric mean (GM) of Mn concentration in blood was 8.98 µg/L. The Mn concentration in blood among males and females were separately 8.14 µg/L and 9.88 µg/L (Z = -18.84, P < 0.01). The GM of Mn concentration in urine was 0.63 µg/L. The Mn concentration in urine among males and females were separately 0.62 µg/L and 0.63 µg/L (Z = -0.67, P > 0.05). The geometric mean (GM) of Co concentration in blood was 0.194 µg/L. The Co concentration in blood among males and females were separately 0.166 µg/L and 0.225 µg/L (Z = -23.04, P < 0.01). The GM of Co concentration in urine was 0.282 µg/L. The Co concentration in urine among males and females were separately 0.260 µg/L and 0.307 µg/L (Z = -7.35, P < 0.01). The GM of Mo concentration in blood was 0.25 µg/L. The Mo concentration in blood among male and female group were separately 0.27 µg/L and 0.23 µg/L (Z = -5.03, P < 0.01). The GM of Mo concentration in urine was 27.7 µg/L. The Mo concentration in urine among males and females were 29.8 µg/L and 25.6 µg/L (Z = -6.31, P < 0.01), respectively.

CONCLUSIONThe Mn, Co and Mo levels in blood and urine varied by gender and area among general population in China, the study provided basic data evidence for the following Mn, Co and Mo biological monitoring studies in near future.

Adolescent ; Adult ; Child ; China ; epidemiology ; Cobalt ; Environmental Exposure ; Environmental Monitoring ; Female ; Humans ; Male ; Manganese ; Middle Aged ; Molybdenum

OBJECTIVETo investigate the level of zinc (Zn) and copper (Cu) in whole blood among general population from 8 provinces in China, and to analyze the characteristics of distribution among different regions.

METHODSThis cross-sectional study was performed in 8 provinces from eastern, middle and western China between 2009 and 2010, including 13 110 subjects from 24 regions, and the blood and urine samples were collected. The ICP-MS was applied to test the content of ICP-MS in blood samples, and the results were used to analyze the characteristics of contents and distributions of Zn and Cu among population from different ages, genders and regions groups.

RESULTSTotally, the mean (95%CI) contents of Cu and Zn in blood were 795 (791-799)µg/L and 3 996(3 976-4 015) µg/L, respectively. The characteristics of distribution of Cu content were as followed, the content of males were lower than it of females (male:767 µg/L; female: 822 µg/L, t = -13.302, P < 0.01). The contents of blood Cu in groups of people aging 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were separately 860(853-868), 758(748-769), 734(728-734), 782(774-790), 811(795-827) and 820(815-826) µg/L. The differences showed statistical significance (F = 78.77, P < 0.01). The blood Cu content of people in eastern China (800µg/L) were also significantly higher than it in middle (774 µg/L)and western China (782 µg/L) (F = 10.94, P < 0.01). Distribution of blood Zn content showed characteristics as follows: the Zn content was higher in males than in females (male 4 085 µg/L and female 3 908 µg/L, t = 8.78, P < 0.01). The contents of blood Zn in groups of people aging 6-12, 13-16, 17-20, 21-30, 31-45 and 46-60 years old were separately 3 306 (3 261-3 350), 3 888 (3 839-3 937), 3 948 (3 902-3 994), 4 272(4 228-4 315), 4 231(4 180-4 281) and 4 250 (4 205-4 294)µg/L, which showed significant statistical differences (F = 233.68, P < 0.01). The blood Zn content of people in eastern China (3 938 µg/L) were significantly lower than it in middle (4 237 µg/L)and western China (4 105 µg/L) (F = 53.16, P < 0.01). In addition, the study also compared the relation between content of Cu and Zn and the frequency of eating seafood. The results found that the frequency of eating seafood could influence the content of Cu and Zn (Cu: F = 13.54, P < 0.01; Zn: F = 200.20, P < 0.01).

CONCLUSIONThe contents and distributions of Cu and Zn in blood differs among people from different groups in ages, genders and regions. The baseline data of this study provided reliable scientific evidence for further research.

Adolescent ; Adult ; Child ; China ; epidemiology ; Copper ; blood ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Zinc ; blood