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.

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.

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.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

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.