OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance （IR） in type 2 diabetes mellitus （T2DM） rats. METHODS T2DM rat model was established by intraperitoneal injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal control group， model group， Qingxue xiaozhi jiangtang formula low-dose and high-dose groups （6.525， 13.05 g/kg， calculated by raw material） and metformin group （positive control， 0.18 g/kg）， with 8 rats in each group. Administration groups were given relevant medicine intragastrically； normal control group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 6 weeks. Body mass and fasting blood glucose （FBG） were determined， and oral glucose tolerance test was conducted. Serum fasting insulin （FINS） level was measured to calculate the insulin resistance index （HOMA-IR） and insulin sensitivity index （ISI）. Additionally， the level of serum lipids， liver function， oxidative stress indicators and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase （PERK） and forkhead box O1 （FOXO1） protein in liver tissue of rats were determined. RESULTS Compared with model group， the body weight， ISI， the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue xiaozhi jiangtang formula high-dose group and metformin group （P＜0.05）； FBG， blood glucose level at 120 minutes of glucose loading， area under the curve of glucose， FINS， HOMA-IR， low-density lipoprotein cholesterol， total cholesterol， triglyceride， alanine transaminase， aspartate transaminase， alkaline phosphatase， malondialdehyde， interleukin-6， tumor necrosis factor-α， and C-reactive protein levels were significantly reduced （P＜ Δ0.05）； the pathological damage of liver tissue had significantlyimproved， and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased （P＜0.05）. CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism， inflammation factor and oxidative stress levels， and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.

Objective:To compare the characteristics of cerebrospinal fluid (CSF) oligoclonal band electrophoresis examination results between patients with multiple sclerosis (MS) and Guillain-Barré syndrome (GBS), and to provide a basis for the differential diagnosis of the two types of neurological demyelinating diseases.Methods:Case analysis.The retrospective study method was used, and the patients who visited Beijing Tiantan Hospital, Capital Medical University from January 2020 to August 2023 were selected as the research subjects, including 70 MS patients[19 males and 51 females, aged 34 (28, 44) years] and 70 GBS patients [44 males and 26 females, aged 50 (36, 61) years]. The oligoclonal band electrophoresis and immunoglobulin G(IgG) index (IgG I) were performed on the clinical specimens from MS and GBS patients, and CSF routine, CSF biochemistry (glucose, chloride, protein), lactate, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), rubella virus (RV), toxoplasma gondii (TOX), Epstein-Barr virus (EBV), and coxsackievirus were detected simultaneously. The enumeration data were treated with the chi-square test. The measurement data didn′t accord with normal distribution, and were treated with the Mann-Whitney U test. Results:The positive rate of oligoclonal band (OCB) electrophoresis in MS and GBS patients were 80.00% (56/70) and 4.29% (3/70), respectively. The positive rate in MS patients was significantly higher than that in GBS patients (χ 2=82.289, P<0.001). The white blood cells count [5.50 (3.00, 11.00)/μl] and the level of chlorine [127 (125, 128) mmol/L] in CSF of MS patients was higher than that of GBS patients [3.50(2.00, 7.00)/μl, 126(124, 128) mmol/L] ( U=-2.245, P<0.05; U=-2.028, P<0.05), while the levels of CSF protein [33.40(27.61, 39.17)mg/L], glucose [3.59(3.36, 3.88) mmol/L], and lactate [1.55(1.40, 1.73) mmol/L] of MS patients were lower than those of GBS patients [6.71(43.78, 138.30) mg/L, 3.97(3.55, 4.54) mmol/L, 1.80(1.60, 2.00) mmol/L]( U=-6.747, P<0.001; U=-3.651, P<0.001; U=-4.531, P<0.001). The levels of IL-6 [3.36(2.34, 5.02) pg/ml], IL-8 [55.40(46.75, 66.40) pg/ml], and TNF-α [5.63(4.25, 6.63) pg/ml] in CSF of MS patients were lower than those of GBS patients [6.12(3.61, 11.73) pg/ml, 120.00(74.90, 187.80) pg/ml, 6.57(5.25, 8.03) pg/ml]( U=-3.463, P<0.05; U=-5.225, P<0.001; U=-2.785, P<0.05). The positive rates of CMV IgG, TOX IgG, and EBVCA IgG in CSF of MS patients were 36.36% (24/66), 0 and 0, respectively,and the positive rates of those of GBS patients were 85.71% (54/63), 30.16% (19/63), and 19.05% (12/63), respectively. The positive rates of CMV IgG, TOX IgG, and EBVCA IgG in CSF of MS patients were significantly lower than those of GBS patients (χ 2=32.839, P<0.001; χ 2=23.343, P<0.001; χ 2=13.861, P<0.001). Conclusions:The MS patients mainly showed the higher positive rates of OCB. The GBS patients showed elevated CSF protein levels but no significant increase in white blood cell count, namely albuminocytologic dissociation in CSF. Meanwhile, the GBS patients showed elevated levels of intrathecal immunity and inflammation indicators, and a higher positive rate of pathogen antibodies.

OBJECTIVE To systematically evaluate the efficacy and safety of the four most common cell therapies， namely purified CD34+ （PCCs）， bone marrow mononuclear cells （BMMNCs）， bone marrow mesenchymal stem cells （BMMSCs） and peripheral blood mononuclear cells （PBMNCs） in the treatment of critical limb ischemia （CLI）. METHODS PubMed， Scopus， Embase， Cochrane Central Register of Controlled Trials （CENTRAL） and Web of Science databases were searched from the establishment of each database to June 2023 to collect randomized controlled trials （RCTs） comparing the efficacy and safety of four different cell therapies， namely PCCs， BMMNCs， BMMSCs and PBMNCs， with other cell therapies or standard therapy （ST） in the treatment of CLI. The outcomes indexes included amputation rate， ankle-brachial index （ABI）， transcutaneous oxygen partial pressure （TCPO2）， ulcer healing rate， pain-free walking distance （PFWD） and angiogenesis. After data extraction from clinical studies that met the inclusion criteria， the RoB 2.0 tool was used to assess the risk of bias， and Stata 15.0 software was used for statistical analysis. RESULTS Meta-analysis included 22 studies， involving 1 318 patients. The treatment groups involved 4 types of cell therapies， namely PCCs，BMMNCs， BMMSCs， and PBMNCs. Network meta-analysis showed that the amputation rates of the four cell therapies groups were lower than that of ST group， and only the difference in PBMNCs group was statistically significant（P＜0.05）. Four cell interventions were better than ST in improving ABI （P＜0.05）， and BMMNCs had the most significant effect on improving ABI. PBMNCs and BMMNCs groups had statistically significant differences in improving TCPO2， compared with ST group and BMMSCs group （P＜0.05）. Four cell interventions were better than ST in improving ulcer healing rate， among which BMMNCs group had no statistical difference with ST group （P＞0.05）； ulcer healing rates of the other three groups were higher than that of ST group （P＜0.05）， and those of PBMNCs and BMMSCs groups were significantly higher than that of BMMNCs group （P＜ 0.05）. BMMSCs group had a significantly better effect on improving the PFWD of patients than the ST group after transplantation， with statistical significance （P＜0.05）， but there was no significant difference in PBMNCs and BMMNCs groups compared with ST group （P＞0.05）. The three cell therapies of BMMSCs， BMMNCs and PBMNCs had a significantly better effect on angiogenesis than the ST group， and the BMMSCs group had a significantly better effect than the BMMNCs and PBMNCs groups， with statistical significance （P＜0.05）. CONCLUSIONS The four cell therapies can improve the prognosis of CLI patients to varying degrees. PBMNCs show the lowest amputation rate after transplantation and have the most significant effect on improving TCPO2 and improving the ulcer healing rate. BMMNCs possess the most significant effect on improving ABI. BMMSCs represent obvious advantages in PFWD and angiogenesis.

Artificial intelligence (AI) has been utilized in soft-tissue analysis and prediction in orthodontic treatment planning, although its reliability has not been systematically assessed. This scoping review was conducted to outline the development of AI in terms of predicting soft-tissue changes after orthodontic treatment, as well as to comprehensively evaluate its prediction accuracy. Six electronic databases (PubMed, EBSCOhost, Web of Science, Embase, Cochrane Library, and Scopus) were searched up to March 14, 2023. Clinical studies investigating the performance of AI-based systems in predicting post-orthodontic soft-tissue alterations were included. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and Joanna Briggs Institute (JBI) appraisal checklist for diagnostic test accuracy studies were applied to assess risk of bias, while the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) assessment was conducted to evaluate the certainty of outcomes. After screening 2500 studies, four non-randomized clinical trials were finally included for full-text evaluation. We found a low level of evidence indicating an estimated high overall accuracy of AI-generated prediction, whereas the lower lip and chin seemed to be the least predictable regions. Furthermore, the facial morphology simulated by AI via the fusion of multimodality images was considered to be reasonably true. Since all of the included studies that were not randomized clinical trials (non-RCTs) showed a moderate to high risk of bias, more well-designed clinical trials with sufficient sample size are needed in future work.
Artificial Intelligence ; Reproducibility of Results

Objective:To investigate the virological testing results of patients with corneal graft at the time of repeat keratoplasty and the diagnostic efficacy of multiple viral examinations.Methods:A case-control study was conducted.A total of 14 consecutive patients diagnosed with corneal graft failure were enrolled as graft failure group from March 2018 to December 2018 in Peking University Third Hospital, and 15 consecutive patients diagnosed with bullous keratopathy (BK) were enrolled as BK group in the meantime.All patients had unilateral involvement and indications for keratoplasty.Serum samples were collected from venous blood on the day of surgery, and specimens of aqueous humor and corneal tissue were obtained during corneal transplantation.Viral DNA in aqueous humor and corneal specimens was detected by real-time polymerase chain reaction (PCR).The level of viral antibodies in serum and aqueous humor was determined by enzyme-linked immunosorbent assay and the Goldmann-Witmer coefficient (GWC) was calculated.The tested viral species included herpes simplex virus (HSV), herpes zoster virus (VZV), and cytomegalovirus (CMV).For graft failure group, the relevance between elevated intraocular pressure, multiple previous keratoplasty surgeries, histories of viral keratitis and any positive result of viral analyses in this study were measured by the kappa consistency test.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University Third Hospital (No.2017299-02).Written informed consent was obtained from each subject.Results:At the time of keratoplasty, 9 out of 14 eyes in the graft failure group tested positive for at least one type of virus, with 6 eyes positive for CMV and 3 eyes positive for VZV.Positive aqueous humor PCR analysis detected VZV in 5 out of 14 eyes.Corneal tissue PCR analysis detected CMV in 5 out of 14 eyes.Positive GWC calculations detected CMV in 3 out of 10 eyes.The concordance between viral DNA and antibody detection was poor.All eyes in BK group were negative for the virological test, except for 2 eyes (2/15) with elevated aqueous humor GWC for CMV.The prevalence of viral infection was 64.2%(9/14) in graft failure group, which was significantly higher than 13.3%(2/15) in BK group ( P=0.014).In graft failure group, 7 eyes (7/14) had elevated intraocular pressure, 3 eyes (3/14) had multiple keratoplasty surgeries, and 6 eyes (6/14) had viral keratitis before this keratoplasty.However, none of these factors showed significant relevance with positive virological results (kappa=0.143, -0.155, -0.286). Conclusions:Viral infection has become a major cause of corneal graft failure.A combination of various virological analyses during keratoplasty can help to clarify the etiology and the viral infection status, and ultimately guide subsequent treatment.

Objective:To investigate the relationship between triglyceride glucose index (TyG) and body inflammation.Methods:The data were obtained from a baseline survey in population in Xi'an in natural population cohort study in northwest China established in 2018-2019. Based on TG and FPG, TyG/TyG-BMI was constructed to reflect insulin resistance (IR) in the body, and systemic immune-inflammation index (SII) reflecting inflammation in the body was constructed using neutrophil, lymphocyte, and platelet counts. A logistic regression model was used to explore the relationship between the TyG and the SII.Results:A total of 11 491 subjects were included in the analysis. After adjusting for covariates, each unit increase in the TyG increased the risk of high SII by 21% ( OR=1.21, 95% CI:1.12-1.30). The risk of high SII in the group with the TyG in Q4 was 1.34 times higher than that in the group Q1 ( OR=1.34, 95% CI:1.18-1.52). Both sensitivity analysis and subgroup analysis further confirmed the stability of the association between the TyG and the SII. In the population with a BMI ranging from 18.5 to 23.9 kg/m 2, for every unit increase in the TyG as a continuous variable, the risk for high SII increased by 31% ( OR=1.31, 95% CI:1.18-1.45). As a categorical variable, the risk for high SII in the Q4 group was 1.52 times higher than that in the Q1 group ( OR=1.52, 95% CI:1.27-1.83). In a population with BMIs ranging from 24.0 to 27.9 kg/m 2, for every unit increase in the TyG as a continuous variable, the risk for high SII increased by 20% ( OR=1.20, 95% CI:1.07-1.35), and there was no significant difference when it was a categorical variable. Conclusions:The increase in IR is closely related to the development of inflammation in the body, and BMI may regulate their relationship. Early prevention of elevated IR levels before overweight or obesity may have a positive effect on the control of inflammation in the body.

Objective:To investigate the value of positron emission tomography/computed tomography (PET/CT) in diagnosis of retroperitoneal lymph node metastasis for early cervical cancer.Methods:Retrospectively analyze the preoperative PET/CT examination results and postoperative pathological results of patients with early cervical cancer who underwent surgical treatment from May 5, 2019 to August 31, 2020, and analyze the clinical characteristics, so as to explore the high risk factors of PET/CT in the diagnosis of retroperitoneal lymph node metastasis.Results:The accuracy, sensitivity, specificity and area under the curve (AUC) of PET/CT in the diagnosis of retroperitoneal lymph node metastasis were 75.2%, 60.0%, 81.3% and 0.707, respectively. Univariate analysis showed that 2009 International Federation of Gynecology and Obstetrics (FIGO) stage, tumor diameter >4 cm, lymphovascular space involvement (LVSI) positive, depth of invasion, high squamous cell carcinoma antigen (SCC-Ag) level and cytological grade were important factors for PET/CT in the diagnosis of retroperitoneal lymph node metastasis ( P<0.05); Multivariate analysis showed that tumor diameter >4 cm was an independent risk factor for PET/CT diagnosis of retroperitoneal lymph node metastasis ( P=0.015). Conclusions:PET/CT has a certain diagnostic value in the evaluation of retroperitoneal lymph node metastasis, but it can not fully reflect the facticity of lymph node metastasis; tumor diameter > 4cm is an independent risk factor for PET/CT in the diagnosis of retroperitoneal lymph node metastasis.

Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.

Objective:To explore the performance of the commonly used whole blood C-reactive protein (CRP) detection systems and give related recommendation on the performance requirements of detection systems.Methods:A total of 7 540 venous blood samples from 26 maternal, child and children′s hospitals were collected to conduct this multi-center study on the analytical performance of 5 commonly used whole blood CRP detection systems from March to April in 2019. The blank check, carryover, repeatability, intermediate precision, linearity, sample stability, influence of hematocrit/triglyceride/bilirubin, comparison with SIEMENS specific protein analyzer and trueness were evaluated. The 5 systems included BC-5390CRP autohematology analyzer, AstepPLUS specific protein analyzer, Ottoman-1000 Automated Specific Protein POCT Workstation, i-CHROMA Immunofluorometer equipment Reader and Orion QuikRead go detecting instrument. The 5 systems were labeled as a, b, c, d and e randomly.Results:Within the 5 systems, all values of blank check were less than 1.00 mg/L, the carryovers were lower than 1.00%. The repeatability of different ranges of CRP concentrations including 3.00-10.00, 10.00-30.00 and>30.00 mg/L were less than 10.00%, 6.00% and 5.00%, respectively, and the intermediate precision was less than 10.00%. The linearity correlation coefficients of the 5 systems were all above 0.975, while the slope was within 0.950-1.050. Whole blood samples were stable within 72 hours both at room temperature (18-25 ℃) and refrigerated temperature (2-8 ℃). The CRP results were rarely influenced by high triglyceride or bilirubin, except for the immmunoturbidimetric test based on microparticles coated with anti-human CRP F(ab) 2 fragments. When triglyceride was less than 15.46 mmol/L, the deviation of CRP was less than 10.00%. When bilirubin was less than 345.47 μmol/L, the deviation of CRP was less than 10.00%. CRP was more susceptible to Hct on the systems without Hct correction. The deviation of CRP between different Hct dilution concentration and 40% dilution concentration can reach as high as 67.48%. The correlation coefficients ( r) of 5 systems were all more than 0.975 in the range of 0-300.00 mg/L compared with Siemens specific protein analyzer. All systems passed the trueness verification using the samples with specified values of 12.89 and 30.60 mg/L. Conclusion:The performance of 5 systems can basically meet the clinical needs, but it is suggested that the whole blood CRP detection system without automatic Hct correction should be modified manually.

Objective:To evaluate the effect of quantitative analysis of optical signal in the near infrared fluorescence molecular navigation surgery for oral squamous cell carcinoma (OSCC).Methods:SCC9, HSC3 and epithelial cell lines (Leuk-1) were co-cultured with indocyanine green (ICG) for 6 hours in vitro in order to verify whether the quantitative analysis of near infrared optical signal could distinguish tumor cells from normal cells. A total of 16 BALB/c male mice (5-6 weeks, 20-25 g) were selected and fed in clean grade equipment and were equally divided into two groups. SCC9 and HSC3 cells were inoculated into the back of each mouse at a concentration of 1×10 6 cells/ml to establish a subcutaneous graft tumor model. The 5 mg/kg ICG was injected into the caudal vein to each of the tumor bearing mouse and the difference between OSCC and normal tissues was then analyzed by near infrared optical signal quantitative analysis (Paired t test). Ten patients with OSCC were enrolled in the Department of Stomatology of the First Affiliated Hospital of Bengbu Medical College from November 2019 to July 2020, including 6 patients with tongue squamous cell carcinoma and 4 patients with buccal squamous cell carcinoma.The patients were 6 males and 4 females and the range of age was from 46 to 71 years with an average age of 58.6 years. These patients were injected ICG (0.75 mg/kg) via the cubital vein at 6-8 h before surgery. Intraoperatively, the fluorescence intensities (FI) of near infrared signal were measured at tumor, peritumor tissues (2.0 cm beyond the tumor boundary) and normal tongue or buccal mucosa respectively. The signal background ratios (SBR) from the three site groups were assessed using one-way ANOVA followed by the Tukey post hoc test for multiple comparisons. Results:In vitro, the levels of near infrared FI in HSC3 and SCC9 groups were higher than that in Leuk-1group ( P<0.01). In vivo, the result showed that the SBR of OSCC and normal tissues was 8.67±0.35. Clinical studies showed that the intensity of tumor [(408.23±101.51) arbitrary units (AU)] was significantly higher than those of peritumoral [(253.12±64.89) AU] and normal tissues [(261.50±80.47) AU] respectively. The SBRs of near infrared FI of tumor and peritumoral tissues, tumor and normal tissues were 1.61±0.53 and 1.56±0.48 respectively, while that of peritumoral and normal tissues was 0.96±0.17. Conclusions:The quantitative analysis of near infrared optical signal could distinguish OSCC from normal cells and could locate the OSCC tissue intraoperatively. Optical signal quantification and ICG near infrared fluorescence molecular technology possessed the feasibility in primary OSCC resection.