ObjectiveThis paper aims to conduct a secondary analysis of a randomized controlled trial on the treatment of myelodysplastic syndrome （MDS） with deficiency of both the spleen and kidney and blockage of toxin and blood stasis with an arsenic-containing traditional Chinese medicine compound， by applying the mixed model for repeated measure （MMRM） and the method of stratified composite outcome with win ratio. The analysis includes the assessment of hematological efficacy and the composite outcome evaluation of adverse reactions， so as to more comprehensively assess the therapy of this regimen. MethodsThe MMRM and win ratio methods were used to evaluate the efficacy of a prospective，multi-center，double-blind，randomized controlled study. The blood routine （hemoglobin concentration，neutrophil count， and platelet count） and biochemical indexes （aspartate aminotransferase，alanine aminotransferase，serum creatinine，and serum ferritin） of the patients were detected at the time of enrollment and at the end of each course of treatment in the laboratory department of Xiyuan Hospital. The patients' syndromes at the time of enrollment and after treatment were recorded and scored according to the therapy standard of traditional Chinese medicine for diseases and syndromes. MMRM was used to analyze the blood routine indexes of the experimental group and the control group. This method has the advantages of high data reliability and dynamic efficacy under intervention and time. The win ratio method was used to evaluate the composite outcome of traditional Chinese medicine syndrome scores and biochemical indexes according to the priority and to verify the clinical safety of arsenic-containing traditional Chinese medicine compound. ResultsThe results of MMRM analysis showed that the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly compared with that before treatment in the group，while that in the placebo group decreased significantly （P<0.01）. When compared with that after treatment in the placebo group，the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly，and the mean difference of least squares （LS） was statistically significant （P<0.01）. When compared with those before treatment in the group，there were no statistically significant differences in the neutrophil count and platelet count in both groups. After treatment，there were no statistically significant differences in the neutrophil count， platelet count， and the mean difference of LS between the two groups. The analysis results of win ratio showed that the group with arsenic-containing traditional Chinese medicine compound had a significant advantage in the comparison of composite outcomes，with a win ratio （95% CI） of 2.01 （1.24-3.27） （P<0.01），and that the possibility of "winning" in terms of safety was 2.01 times that of the placebo group. The safety advantage of the group with arsenic-containing traditional Chinese medicine compound mainly came from the traditional Chinese medicine syndrome scores，renal function indexes， and iron reserve capacity indexes，and the number of winning times was less than that of losing times in the comparison of liver function outcomes. ConclusionThe MMRM analysis proves that the arsenic-containing traditional Chinese medicine compound can significantly improve the hemoglobin concentration of patients with myelodysplastic syndrome with refractory cytopenia and multilineage dysplasia （MDS-RCMD） of the type of deficiency of both the spleen and kidney and blockage of toxin and blood stasis. This conclusion is not interfered with by time trends and individual relationships and methodologically improves the credibility of the therapy of the arsenic-containing traditional Chinese medicine compound in treating MDS. Four outcomes are evaluated by the win ratio method，namely traditional Chinese medicine syndromes，liver function，renal function， and iron reserve capacity，proving that the arsenic-containing traditional Chinese medicine compound has the comprehensive advantages of improving the survival quality of the patients and reducing adverse reactions. The win ratio outcome provides clear comparative indexes for the evaluation of adverse reactions，making it easier for regulatory authorities，medical staff， and patients to understand the safety of the arsenic-containing traditional Chinese medicine compound in clinical application.

Antibody-negative autoimmune encephalitis （AE） in children poses certain challenges for clinical diagnosis and treatment due to the lack of characteristic autoantibodies. This study conducts a retrospective analysis of the clinical data of a boy， aged 7 years， who had the main manifestations of “irritability， vomiting， pyrexia， and lethargy”. Video electroencephalography showed diffuse slow waves， with the presence of type 2 cerebrospinal fluid oligoclonal bands， and the boy was tested negative for related autoantibodies in blood and cerebrospinal fluid. Finally the boy was diagnosed with antibody-negative AE. After admission， the boy received first-line immunotherapy with methylprednisolone and intravenous immunoglobulin， combined with tocilizumab for intensive treatment， and the symptoms were rapidly relieved. At 1 week after discharge， the boy experienced memory loss， and head MRI suggested cerebral atrophy. After 1 month of adjuvant hyperbaric oxygen therapy， the boy’s memory recovered to the level before disease onset， and reexaminations of MRI and video electroencephalography obtained normal results.No recurrence was observed during follow-up for 6 months， and the boy achieved satisfactory academic performance.This case suggests that for children with antibody-negative AE， first-line immunotherapy combined with tocilizumab can rapidly control inflammation， and the addition of hyperbaric oxygen therapy can effectively improve subsequent cerebral structural and cognitive abnormalities， with few adverse reactions， which provides a new clinical approach for the treatment of this type of disease.

Objective: To present the plotting of trend analysis charts and the application of multi-rule trend analysis method for monitoring the quality of whole blood, washed red blood cells, and leukocyte-depleted suspended red blood cells. Methods: Samples of whole blood, washed red blood cells, and leukocyte-depleted suspended red blood cells were collected in accordance with relevant protocols and requirements. The results of blood quality testing were compiled. The trend line charts were plotted for the deviation rates of volume, hemoglobin (Hb) content, supernatant protein content, and leukocyte residual count. In addition, the trend line chart were plotted for hematocrit and post-storage hemolysis rate. Results: The trend analysis rules for the deviation rate of volume from the standard were: 1 categorized as out-of-control, (3 of 4) as warning, R as warning, 8 as alert, and 12 as alert. For Hb content deviation rate, the rules were: <0% categorized as out-of-control; <20% but ≥0% (for whole blood) or <10% but ≥0% (for washed red blood cells and leukocyte-depleted suspended red blood cells) as a warning. For supernatant protein content deviation rate, the rules were: ≥0.0% as out-of-control, and >-10% but <0.0% as a warning. For hematocrit, the rules were: 1 as out-of-control and (3 of 4) as warning. For leukocyte residual count deviation rate, the rules were: >0.0% as out-of-control, and >-10% but ≤0.0% as a warning. For post-storage hemolysis rate, the rule was: ≥0.8% out-of-control. Conclusion: The application of multi-rule trend analysis facilitates the timely identification of trend abnormalities and factors causing deviations in the collection and preparation processes of whole blood, washed red blood cells, and leukocyte-depleted suspended red blood cells, thereby providing reliable numerical evidence for their correction and adjustment.

Objective To comprehensively evaluate the causal relationship between gut microbiota and 9 respiratory diseases, explore whether there are common mechanisms among these 9 respiratory diseases, and delves into the potential commonalities of pre-chronic obstructive pulmonary disease (pre-COPD) by focusing on COPD, emphysema, and chronic bronchitis. Methods Mendelian randomization was used to explore the causal relationship between gut microbiota and 9 respiratory diseases, sensitivity analysis was conducted, and robustness was verified. Single nucleotide polymorphisms of common gut microbiota were mapped to genes to explore their common mechanisms. Results Mendelian randomization studies found that 66 gut microbiota had a causal relationship with 9 respiratory diseases, and 15 gut microbiota might be potential common mechanisms for these 9 respiratory diseases, with a total of 85 potential genes. GO functional enrichment analysis found that these genes were mainly enriched in biological functions such as synaptic transmission, synaptic membrane, cytokine activity, and growth factor binding. KEGG enrichment analysis showed that these genes were mainly enriched in glutamatergic synapses, relaxin signaling pathway, calcium signaling pathway, Rap1 signaling pathway, and PI3K-Akt signaling pathway. Allisonella and Prevotellaceae might be protective factors for pre-COPD, while Howardella might be a risk factor. Ten protective genes and six risk genes for the pre-COPD were identified. Conclusion This study further confirms the correlation between the lung-gut axis and the lung-colon connection, explores the potential common mechanisms of 9 respiratory diseases, investigates the potential mechanisms of pre-COPD based on the common gut microbiota of COPD, chronic bronchitis, and emphysema, and provides some ideas for the early prevention and treatment of COPD, and diagnosis of pre-COPD from the perspective of gut microbiota.

ObjectiveTo assess the performance of preoperative serum Golgi protein 73 （GP73） in diagnosing liver fibrosis degree in patients with resectable hepatocellular carcinoma （HCC）， to investigate its value in predicting postoperative survival， and to provide a basis for risk stratification and individualized decision-making in this population. MethodsA total of 631 patients with HCC who underwent liver resection at The First Hospital of Jilin University from March 1， 2009 to December 31， 2022 were enrolled. The demographic， pathological， and serological features of the patients were collected， and the serum level of GP73 was measured before surgery. Scheuer score determined by liver biopsy was used as the gold standard for diagnosing liver fibrosis； the Spearman correlation analysis was used to investigate the correlation between GP73 and liver fibrosis； the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to assess the value of serum GP73 and compound serological markers in the diagnosis of liver fibrosis， and the Delong test was used for comparison of AUC. With all-cause mortality as the outcome， X-Tile 3.6.1 software was used to determine the optimal cut-off value of GP73； the univariate and multivariate Cox regression analyses were used to identify independent influencing factors for prognosis， and a nomogram model was constructed. Ten-fold cross-validation was used for internal validation； index of concordance （C-index）， integrated discrimination improvement （IDI） index， and net reclassification improvement （NRI） index were calculated； calibration curve and decision curve analysis were used to assess the predictive performance of the model. ResultsThe serum level of GP73 was positively correlated with Scheuer liver fibrosis stage （r_s=0.255， P<0.001）. Serum GP73 had a significantly higher AUC than gamma-glutamyl transferase-to-platelet ratio （0.704 vs 0.634， Z=2.00， P=0.046） and S index （0.704 vs 0.637， Z=1.98， P=0.048） in the diagnosis of significant liver fibrosis， with no significant difference compared with aspartate aminotransferase-to-platelet ratio index （AUC=0.722） and fibrosis-4 index （AUC=0.695） （both P>0.05）. During a median follow-up time of 48.66 months， 239 patients （37.9%） died. GP73 had an optimal cut-off value of 65 ng/mL in predicting postoperative mortality in patients with resectable HCC， and high GP73 expression （≥65 ng/mL） alone achieved a C-index of 0.617 for predicting the prognosis of HCC patients， which was better than the C-index of 0.551 for Barcelona Clinic Liver Cancer （BCLC） stage （P<0.001）. The multivariate Cox regression analysis showed that serum GP73 （hazard ratio ［HR］=2.56， 95% confidence interval ［CI］： 1.86 — 3.52， P<0.001）， sex （HR=1.58， 95%CI： 1.10 — 2.28， P=0.014）， vascular invasion （HR=1.69， 95%CI： 1.30 — 2.21， P<0.001）， total bilirubin （HR=1.49， 95%CI： 1.16 — 1.93， P=0.002）， and maximum tumor diameter （HR=1.07， 95%CI： 1.04 — 1.11， P<0.001） were independent risk factors for all-cause mortality after hepatectomy in patients with HCC. In order to assess whether the addition of GP73 to the other four variables could further improve model performance， the model based on GP73， sex， vascular invasion， total bilirubin， and maximum tumor diameter was defined as the GP73-included model， and the model based on all five variables except GP73 was defined as the GP73-excluded model. The GP73-included model achieved an AUC of 0.704 （95%CI： 0.656 — 0.753） for predicting 5-year survival rate after surgery， and ten-fold cross-validation showed that this model had a mean C-index of 0.716 （95%CI： 0.682 — 0.750）， which was higher than the C-index of the GP73-excluded model （C-index=0.682， 95%CI： 0.645 — 0.719， P=0.008） and BCLC stage （C-index=0.551， 95%CI： 0.523 — 0.580， P<0.001）. Compared with the GP73-excluded model， the GP73-included model yielded an IDI index of 0.039 （95%CI： 0.016 — 0.069， P<0.001） and an NRI index of 0.259 （95%CI： 0.179 — 0.335， P<0.001）， and compared with BCLC stage， the GP73-included model had an IDI index of 0.112 （95%CI： 0.069 — 0.163， P<0.001） and an NRI index of 0.272 （95%CI： 0.169 — 0.380， P<0.001）. Calibration curve and decision curve analyses showed that the GP73-included model had good calibration and net clinical benefit. ConclusionGP73 can be used as a serological biomarker for diagnosing liver fibrosis in patients with resectable HCC， and preoperative GP73 level has a certain value in predicting the survival of these patients after hepatectomy. The integrated prognostic model incorporating GP73 can help to optimize postoperative risk stratification， thereby providing a basis for decision-making in precise treatment of HCC.

To address the challenges faced by current brain midline segmentation techniques, such as insufficient accuracy and poor segmentation continuity, this paper proposes a deep learning network model based on a two-stage framework. On the first stage of the model, prior knowledge of the feature consistency of adjacent brain midline slices under normal and pathological conditions is utilized. Associated midline slices are selected through slice similarity analysis, and a novel feature weighting strategy is adopted to collaboratively fuse the overall change characteristics and spatial information of these associated slices, thereby enhancing the feature representation of the brain midline in the intracranial region. On the second stage, the optimal path search strategy for the brain midline is employed based on the network output probability map, which effectively addresses the problem of discontinuous midline segmentation. The method proposed in this paper achieved satisfactory results on the CQ500 dataset provided by the Center for Advanced Research in Imaging, Neurosciences and Genomics, New Delhi, India. The Dice similarity coefficient (DSC), Hausdorff distance (HD), average symmetric surface distance (ASSD), and normalized surface Dice (NSD) were 67.38 ± 10.49, 24.22 ± 24.84, 1.33 ± 1.83, and 0.82 ± 0.09, respectively. The experimental results demonstrate that the proposed method can fully utilize the prior knowledge of medical images to effectively achieve accurate segmentation of the brain midline, providing valuable assistance for subsequent identification of the brain midline by clinicians.
Humans ; Brain/diagnostic imaging* ; Deep Learning ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Magnetic Resonance Imaging/methods* ; Neural Networks, Computer

Diabetic foot (DF) is one of the most serious chronic complications of diabetes. The incidence rate among global diabetes patients is as high as 15% to 25%, and about 50% of patients will develop contralateral foot ulcers within 5 years after the first unilateral ulcer. As a non-invasive prevention and control solution, the application progress of functional insoles is mainly reflected in the following aspects:(1) Material innovation. The application of new composite materials and smart materials has significantly enhanced the pressure reduction effect and comfort. (2) Structural optimization. The development of multi-layer design and local pressure reduction structure has achieved more precise pressure distribution regulation. (3) Manufacturing process. 3D printing and parametric design have enabled the personalized customization of functional insoles. (4) Intelligent monitoring. It integrates functions such as pressure sensing and temperature monitoring, achieving real-time monitoring and early warning of foot conditions. Clinical research has confirmed that personalized functional insoles could reduce the incidence of foot ulcers and shorten the healing time of ulcers. At present, the research hotspots mainly focus on the development of smart materials, the construction of multi-functional integration and remote monitoring systems. However, in-depth research is still needed in the aspects of biomechanical mechanisms, standardized evaluation systems and long-term efficacy assessment. The development of future functional insoles should focus on the coordinated advancement of "personalization-intelligence-standardization", with the aim of providing more effective solutions for the prevention and treatment of DF.
Humans ; Diabetic Foot/therapy* ; Foot Orthoses

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins