ObjectiveTo explore the mechanism of Shaoyaotang in the prevention and treatment of colitis-associated carcinogenesis （CAC） based on myeloid-derived suppressor cells （MDSCs）-related immunosuppressive microenvironment. MethodsA total of 140 six-week-old SPF FVB male mice were randomly divided into seven groups： Blank group， Shaoyaotang without model group （7.12 g·kg^-1）， model group， sulfasalazine group （0.52 g·kg^-1）， Shaoyaotang low-dose group （3.56 g·kg^-1）， Shaoyaotang medium-dose group （7.12 g·kg^-1） and Shaoyaotang high-dose group （14.24 g·kg^-1）， with 20 mice in each group. The blank control group and the Shaoyaotang without model group received a single intraperitoneal injection of physiological saline （10 mg·kg^-1）， while the other five groups were given a single intraperitoneal injection of azoxymethane （AOM） （10 mg·kg^-1）. After 1 week， the mice were given drinking water containing 2% dextran sulfate sodium （DSS） for 1 week， followed by normal drinking water for 2 weeks. This cycle was repeated three times over a total period of 14 weeks to establish the CAC mouse model. Each group was administered gavage once daily for 2 weeks starting on the 14^th day of the experiment， followed by three times a week until the end of the experiment. The body weight of the mice was recorded weekly. Mice were sacrificed on the 28^th and 98^th days of the experiment. After dissection， the colon length， colon weight， spleen weight， tumor size， and tumor number were measured. Hematoxylin and eosin （HE） staining was used to assess the pathological morphology of colon tumor tissue. Flow cytometry was used to detect MDSCs， regulatory T cells （Tregs）， CD4⁺ T cells， CD8⁺ T cells， and the CD4⁺/CD8⁺ T cell ratio in the spleen. Immunohistochemistry was used to detect the expression levels of programmed cell death protein-1 （PD-1）， programmed cell death ligand 1 （PD-L1）， phosphorylated AMP-activated protein kinase （p-AMPK）， phosphorylated nuclear factor-κB （p-NF-κB）， and hypoxia-inducible factor 1α （HIF-1α） in the colon tissue. ResultsOn day 14， compared with the blank group， the body weight of the model group was significantly reduced （P<0.01）， reaching its lowest point on day 28 （23.39 ± 0.95 ） g. On days 28 and 98， compared with the blank group， the colon length in the model group was significantly shortened （P<0.01）， the colon index significantly increased （P<0.01）， the spleen index significantly increased （P<0.01）， and the tumor load significantly increased （P<0.01）. HE staining showed that in the model group， tumor cells， a large number of inflammatory cell infiltrates， goblet cell disappearance， and crypt loss were observed. In each dose group of Shaoyaotang， the damage to the colonic mucosa， inflammatory cell infiltration， and crypt structure destruction were alleviated. Compared with the model group， the body weight of mice in each dose group of Shaoyaotang increased. On day 98， the colon length was significantly increased （P<0.01）， the colon index significantly decreased （P<0.01）， the spleen index significantly decreased （P<0.01）， and the tumor burden significantly decreased （P<0.01） in each Shaoyaotang dose group. On days 28 and 98， MDSCs and Tregs in the spleen of the medium- and high-dose Shaoyaotang groups were significantly reduced （P<0.01）， while CD4⁺ T cells and the CD4⁺/CD8⁺ T cell ratio were significantly increased （P<0.01）. The proportion of CD8⁺ T cells in the spleen and the expression levels of PD-1 and PD-L1 in the colon tissues of mice in each Shaoyaotang dose group were significantly increased to varying degrees （P<0.05， P<0.01）. On days 28 and 98， the expression of p-AMPK-positive cells in the colon tissue of the medium- and high-dose Shaoyaotang groups was significantly increased （P<0.01）， while the expression of p-NF-κB and HIF-1α was significantly reduced （P<0.01）. ConclusionShaoyaotang can regulate MDSC recruitment and modulate the immune function of T lymphocyte subsets to inhibit the occurrence and development of AOM/DSS-induced CAC in mice. The mechanism may be related to the activation of the AMPK/NF-κB/HIF-1α pathway.

It is proposed that cold qi-induced accumulation encapsulates the core pathogenesis of the inflammation-cancer transformation in inflammatory bowel disease （IBD）. Cold pathogens may serve as the initiating factor. When first invading the intestines， cold pathogens obstruct the flow of qi； over time， the lingering cold impairs the middle jiao （焦）， eventually leading to the accumulation of cold-phlegm and blood stasis. Based on the progressive nature of this transformation， the process can be divided into three stages， active stage， remission stage， and carcinogenic stage. In the active stage， the main pathogenesis involves stagnation of cold qi and accumulation of damp-heat in the intestines； in the remission stage， cold qi impairs the spleen， disrupting its transport and transformation functions； and in the carcinogenic stage， the mechanisms include cold-induced accumulation， phlegm accumulation from cold， and stagnation of cold and blood stasis. Accordingly， the treatment strategies are proposed.In the active stage， regulating qi， relieving stagnation， and harmonizing cold and heat； in the remission stage， warming yang， dispersing cold， tonifying qi， and strengthening the spleen； and in the carcinogenic stage， promoting qi circulation， dispersing cold， resolving phlegm， activating yang， and eliminating stasis to remove accumulation. These approaches aim to interrupt the transformation of IBD into colorectal cancer.

Objective:To explore the clinical characteristics of interleukin-6 (IL-6) and interleukin-8 (IL-8) in cerebrospinal fluid (CSF) of children with bacterial meningitis (BM) and provide reference for clinical diagnosis and treatment of BM.Methods:The clinical data of BM children hospitalized in Women and Children′s Medical Center Affiliated to Guangzhou Medical University from December 2019 to March 2022 were collected and retrospectively analyzed in this case series study.Cytokines in CSF of these children were detected at least twice during the treatment. t test, Mann-Whitney test or analysis of variance were carried out for statistical analysis. Results:There were 40 patients included in this study.The age of onset was 2(1, 8) months, ranging from 2 days to 8 years, and the length of time from onset to hospitalization was (15±17) days, ranging from 1 day to 69 days.The main symptoms at the onset were fever (40 cases, 100%), poor mental state (16 cases, 35.0%), convulsion (9 cases, 22.5%), and vomiting (9 cases, 22.5%).According to pathogens, the patients were divided into the Streptococcus agalactia group (GBS group, 9 cases), Streptococcus pneumoniae group (SP group, 9 cases), other bacteria group (9 cases), and unknown bacteria group (13 cases).The levels of cytokines in the CSF of BM children were increased, along with significantly elevated levels of IL-6 and IL-8 within 1 st week of BM, followed by the peak at 2 nd-3 rd weeks, and then levels of IL-6 and IL-8 presented an overall decreasing trend with the progression of BM.The level of IL-6 in CSF of 10 cases significantly decreased in the 4 th week of BM [within 2 weeks: 773.5(164.1, 1 781.2) ng/L vs. 4 th week: 10.8(2.2, 21.1) ng/L, P=0.005].Such statistical differences didn′t occur to the level of IL-8 [within 2 weeks 182.9(33.6, 657.7) ng/L vs. 4 th week: 92.9(22.6, 226.6) ng/L, P=0.303].After effective antibiotic therapy, 6 patients had elevated white blood cell count in CSF during the 4 th-20 th weeks, with or without repeating intermittent fever.Among them, 4 cases of GBS and 1 case of SP were negative for pathogens in CSF during the retest after treatment, and the levels of IL-6 and IL-8 [(149.1-4 218.6) ng/L and (124.2-1 890.3) ng/L, respectively] in CSF were elevated.Low-dose glucocorticoid was administered for anti-inflammatory treatment, with additional gamma globulin for 1 case and Ibuprofen instead for 1 case.Subsequently, the fever completely subsided.The white blood cell count in CSF decreased significantly ( P=0.024). Conclusions:The levels of IL-6 and IL-8 in CSF increase significantly in the acute phase of BM and generally decrease with the progression of BM.If they are still significantly elevated in the later course of BM, it should be noted that an intracranial hyperinflammatory response may occur, especially when the pathogenic bacteria are GBS or SP.

Objective:To evaluate the feasibility of using a visual positioning system for both motion phantom and clinical quality control.Methods:A phantom experiment was conducted using the Dynamic Thorax Phantom from CIRS. Different ranges of motion were simulated to assess the discrepancies between camera-recorded positions and actual movements. Visual markers were also attached to the treatment bed and the collimator head, and their movements were simulated as part of the experiment. The experiment was repeated for three times. Discrepancies between system measurements and manual measurements were recorded and analyzed to assess the accuracy and reliability of the system.Results:In the motion phantom test, the deviation between the actual motion distance of the phantom and the system's recorded measurement was (0.18±0.07) mm. For linear motion analysis along the X, Y, and Z axes on the treatment table, the measurement errors were (0.14±0.08) mm, (0.15±0.09) mm, and (0.16±0.08) mm, respectively. Additionally, the measurement error in the rotational direction of the treatment couch was 0.18°±0.09°. For the rotational direction of the collimator head, the measurement error was 0.11°±0.02°. Conclusion:The system demonstrates good accuracy and stability, and has potential clinical application value.

Objective:To explore the application effect and evaluation of virtual reality technology in oral implant therapy training.Methods:In November 2018, one adult patient (female, 36 years old) with missing right mandibular first molar was treated in the Department of Implantology, School and Hospital of Stomatology, Fujian Medical University. The three-dimensional virtual models of mandible and implant surgery tools were established, and the virtual reality software (Unity 3D 5.5.1) was imported. Combined with the virtual reality head mounted display, a virtual reality training system simulating the dental implant treatment process was independently developed. Ten refresher doctors and 20 graduate students in Department of Implantology, School and Hospital of Stomatology, Fujian Medical University from September 2018 to December 2019 were recruited as the experimental objects (no clinical experience was found). According to the level and seniority of doctors, they were randomly divided into virtual training group and conventional training control group, which made the two groups comparable, with 15 in each group. Subjective scores (including anatomical structure, surgical field of vision, cavity preparation, implant placement and process mastery) were given after the corresponding training in the two groups, and the virtual reality training system was used to test. The mesial and distal direction, buccolingual direction, depth and angle deviation of implants before and after the training were analyzed, and the differences between the two groups were compared.Results:The subjective scores of five dimensions in the virtual training group were significantly higher than those in the conventional training control group ( P<0.05). In the virtual training group, the mesial and distal, buccolingual, depth and angle deviation of implants were (0.73±0.33), (0.78±0.41), (0.61±0.32) mm and 6.66°±3.87°. All of them were significantly lower than those in the control group [(0.85±0.32), (1.12±0.38), (0.89±0.24) mm and 9.68°±3.74°] ( P<0.05). Conclusions:The self-developed virtual reality system of oral implant has good application effect, good operability and predictability. It can be effectively carried out in implant education and training, and it can strengthen skills of doctors, and is conducive to the practical operation.

Objective To evaluate the efficacy and safety of combined use of ticagrelor and cilostazol for patients with acute coronary syndrome (ACS) complicated with upper digestive tract diseases following percutaneous coronary intervention ( PCI).Methods A total of 262 consecutive ACS patients complicated with upper digestive tract diseases followed-up for one-year after PCI were included in this study.The patients were allocated into control group (combined use of ticagrelor and aspirin , n＝184) and cilostazol group ( combined use of ticagrelor and cilostazol , n ＝78) for antiplatelet treatment.The basic characteristics of the patients , change of the treatment regimens , cardiovascular events and hemorrhagic events were compared between two groups .Results After one year of follow-up, 16.8%(31/184)patients in control group and 3.8%(3/78)in cilostazol group changed antiplatelet regimens (χ2＝8.200,P＝0.004).There was no statistical difference in use of statins and ACEI/ARB between two groups(P＞0.05).The rate of proton pump inhibitor use in control group was significantly higher than that in cilostazol group [82.1%(151/184) vs.52.6%(41/78), χ2＝24.35, P＝0.000].However, the dosage of β-blockers in cilostazol group was significantly higher than that in control group [(39.1 ±12.4) mg vs.(28.6 ±10.1) mg, t ＝7.174,P＝0.000].No statistical difference was found in total cardiovascular events between two groups [21.7%(40/184) vs.12.8%(10/78),χ2＝2.822,P＝0.121].The incidence of gastrointestinal hemorrhage in control group was significantly increased compared with cilostazol group [12.0%(22/184) vs.2.6%(2/78),χ2＝5.807,P ＝0.018], however, there was no significant difference in hemorrhagic events concerning the thrombolysis for myocardial infarction between two groups [17.4%(32/184) vs.9.0%(7/78), χ2＝3.063,P＝0.089].Conclusion Combined use of cilostazol and ticagrelor is effective and safe for ACS patients with gastrointestinal hemorrhage or a higher risk of hemorrhage .

Objective To compare the efficacy of cardiac resynchronization therapy (CRT) on chronic heart failure (CHF) patients with different left bundle branch block (LBBB) morphologies. Methods Patients(n=45)who were treated with CRT were enrolled. According to the intrinsic ECG morphologies, patients were divided into 1)genuineLBBB group (n=32) who present negative dominant V1 and V2 lead wave (QS or rS);mid-QRS notching or slurring in at least 2 leads of Vl, V2, V5, V6, I and aVL as well as QRS duration≥140 ms in male or≥130 ms in female and 2)falseLBBB group (n=10) who meet traditional standards but fail to meet“genuine”LBBB diagnostic standard. The QRS duration, echocardiographic indi?ces and New York Heart Association (NYHA) Functional Classification were evaluated at the 12 months follow-up. CRT re?sponder was defined as patient with≥1 decrease in NYHA class and/or with≥15%reduction in left ventricular end-systolic volume (LVESV). CRT super-responder was defined as patient with≥30%reduction in LVESV. Results There was no dif?ference in basic characteristics of patients between groups. At the 12 months follow-up, 20 patients in genuine LBBB group and 6 patients infalseLBBB group were identified as responders (P>0.05). Compared with those infalseLBBB group, the responders ingenuineLBBB group showed better improvement in left ventricular ejection fraction and left ven?tricular end diastolic diameter (LVEDD) (both P<0.05). Conclusion Left bundle branch block morphology is less predic?tive for the efficacy of CRT. However, patients who show response to CRT withgenuineLBBB profile may get more bene?fits from CRT treatment than the patients withfalseLBBB profile.

BACKGROUNDPericytes, located on microvessels, help to maintain vascular stability and blood-brain barrier integrity. The influence of pericytes on microvessels after spinal cord injury (SCI) is less clear. Therefore, the aim of this study was to investigate whether pericytes took a protective effect on microvessels in melatonin-treated SCI.

METHODSC57BL/6 mice were randomly divided into three groups: sham group, SCI group, and melatonin group (n = 27 per group). Functional recovery was evaluated using the Basso Mouse Scale. Motor neurons were observed using hematoxylin and eosin staining. Pericyte coverage was analyzed using immunofluorescence. Permeability of blood-spinal cord barrier (BSCB) was assessed by administration of Evan's Blue. Protein levels of occludin, aquaporin-4 (AQP4), angiopoietin-1 (Ang1), intercellular cell adhesion molecule-1 (ICAM-1), Bcl-2, and Bax were determined using Western blotting. Mimicking the pathological conditions of SCI, melatonin-treated primary pericytes were subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Secretion of Ang1 was analyzed using an enzyme-linked immunosorbent assay, and the expression of ICAM-1 was detected by immunofluorescence.

RESULTSMelatonin treatment improved locomotor functional outcome and rescued motor neurons. Pericyte coverage was significantly reduced after SCI; melatonin treatment alleviated the loss of pericyte coverage and rescued perfused microvessels 7 days after injury. The permeability of BSCB and loss of occludin were attenuated, and edema formation and upregulation of AQP4 were inhibited, after melatonin treatment. The expression of Ang1 and Bcl-2 was improved, while the expression of ICAM-1 and Bax was inhibited, in melatonin-treated SCI mice. Furthermore, the secretion of Ang1 was increased and the expression of ICAM-1 was inhibited in melatonin-treated pericytes after OGD/R.

CONCLUSIONSMelatonin ameliorated the loss of blood vessels and disruption of BSCB to exert a protective effect on SCI, which might be mediated by increased pericyte coverage. The upregulation of Ang1 in pericytes could inhibit inflammation and apoptosis to protect the microvessels.

Angiopoietin-1 ; metabolism ; Animals ; Enzyme-Linked Immunosorbent Assay ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Melatonin ; pharmacology ; therapeutic use ; Mice ; Mice, Inbred C57BL ; Microvessels ; cytology ; Occludin ; metabolism ; Pericytes ; drug effects ; metabolism ; Random Allocation ; Spinal Cord Injuries ; drug therapy ; metabolism

Objective To investigate the neural circuit of inhibitory control in late-onset depressed patients(LOD) by functional magnetic resonance imaging(fMRI). Methods Fourteen late-onset depressed patients (LOD group) and thirteen elderly healthy subjects( control group) were recruited. The two groups were age, gender, and education matched. All the subjects performed a visual Go/Nogo task during the fMRI scan. Erect or inverted isosceles triangular figures were used for stimuli. The two groups were instructed to press a button as quickly and correctly as possible when the erect triangular figures(Go) were presented, but not to response when the inverted triangular figures(Nogo) were presented. The differences of brain activation between the two groups were compared. Results ( 1 ) During Go trials, there were no significant differences in reaction time and hit rate between the two groups (P ＞ 0.05 ). During Nogo trials, however, the late-onset depressed patients showed much higher false alarm rate(0.09 ±0.06) compared with control group(0.04 ±0.02) (P＜0.05＝. (2) During Go trials , LOD group showed significantly greater activity in left postcentral gyrus, left inferior parietal lobule, right precentral gyrus, left paracentral lobule, right inferior parietal lobule, right anterior cingulate cortex, left middle frontal gyrus, right middle frontal gyrus, right superior frontal gyrus compared with the control group. Whereas during Nogo trials, LOD group exhibited greater activity in left inferior parietal lobule and left middle frontal gyrus compared with the control group. Conclusion This study suggests that inhibitory control dysfunction in late-onset depressed patients may be closely related to frontostriatal circuit impairment. Over activation in left middle frontal gyrus, right middle frontal gyrus and right anterior cingulate cortex may contribute to the pathogenesis of late-onset depression.

This study explored the accuracy of using visual evoked potentials (VEP) technology for visual acuity estimation. The enrolled 726 patients with post-traumatic unilateral decrease in visual acuity included the injured eyes served as the experimental group, and the healthy eyes as the control group. The least signal visual angle (LSVA), and amplitude and latency of P(100) were chosen as test indexes. The results under different experimental conditions were recorded by PRVEP technology. All data collected were processed and analyzed by SPSS software. The results showed that the coincidence between subjective and VEP visual acuity was 96.7% in control group, but there was very significant difference in experimental group. It was concluded that with the regression formulation for the amplitude of P(100) and vision under LSVA, visual acuity can be estimated more accurately and impartially.