OBJECTIVE: To investigate the efficacy and safety of stanozolol combined with avatrombopag in the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients with relapsed/refractory tumors. METHODS: Twenty-five patients with relapsed/refractory CIT admitted to the Hematology Department of Xiyuan Hospital, China Academy of Chinese Medical Sciences between March 2023 to December 2023 were enrolled. These patients received a combined therapy of stanozolol and avatrombopag. The clinical efficacy, onset time, changes in platelet levels and blood cell counts before and after treatment, and adverse reactions of patients were evaluated. RESULTS: The combination therapy demonstrated remarkable efficacy with a total effective rate of 100%. Among the 25 patients, 19 achieved complete remission and 6 achieved partial remission. The median onset time was 42.5（range: 35-48）days. The average platelet count of the 25 patients increased from (25.73±17.75)×10⁹/L before treatment to (146.4±49.59)×10⁹/L after 3 months of treatment, with a statistically significant difference ( P < 0.05). 18 patients who previously required platelet transfusion were all weaned off platelet transfusion after 3 months of treatment, with a median time to be free from platelet transfusion was 26 (range: 18-51) days. During the treatment, both neutrophils and hemoglobin exhibited various degrees of elevation. Two patients experienced a slight increase in alanine aminotransferase(ALT) levels, which normalized after treatment with oral hepatoprotective drug. One patient had a PLT increase exceeding 350×10⁹/L, and the treatment with avatrombopag was suspended, and aspirin and other drugs were given to prevent thrombosis. No thrombose events or CIT-related bleeding events were observed in all patients. CONCLUSION The combination therapy of stanozolol and avatrombopag is significantly effective for treating relapsed/refractory CIT patients, with a high response rate and good safety, making it a suitable clinical treatment option.
Humans ; Thrombocytopenia/chemically induced* ; Stanozolol/therapeutic use* ; Male ; Female ; Neoplasms/drug therapy* ; Middle Aged ; Thiophenes/therapeutic use* ; Adult ; Platelet Count ; Treatment Outcome ; Antineoplastic Agents/adverse effects* ; Recurrence ; Thiazoles

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Objective To investigate the role of the neutrophil-to-lymphocyte ratio(NLR)in predicting the in-hospital mortality risk of patients with acute aortic dissection(AAD)in multicenter hospitals.Methods A multicenter retrospective cohort study was conducted.Clinical data were collected from 2642 AAD patients who were hospitalized in five teaching hospitals:Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,Henan Provincial People's Hospital,Fuwai Central China Cardiovascular Hospital,the Third Affiliated Hospital of Xinxiang Medical University,and the Second Affiliated Hospital of Chongqing Medical University between August 2010 and December 2021.According to the quartiles of serum NLRlevels,the patients were divided into four groups:first quartile(Q1,n=660),second quartile(Q2,n=661),third quartile(Q3,n=661),and fourth quartile(Q4,n=660).The clinical characteristics and biochemical indicators of each group were compared.Partial correlation analysis was used to assess the relationship between NLR and cardiovascular parameters.Restricted cubic splines,Kaplan-Meier survival analysis,and Cox regression models were employed to evaluate the association between NLR levels and in-hospital mortality risk in AAD patients.Results The median age of all patients was 54[interquartile range(IQR):46-63]years,including 2096 males and 546 females.Compared with Q1-Q3 groups,patients inQ4group had a lower incidence of smoking history and diabetes history,and were more likely to have DeBakey type Ⅰ AAD(P＜0.05).Additionally,the levels of aspartate aminotransferase,high-density lipoprotein cholesterol,creatinine,and D-dimer in Q4 group were higher,while the levels of triglycerides and C-reactive protein(CRP)were lower(P＜0.01).The results of partial correlation analysis showed that the plasma NLR level was positively correlated with D-dimer(r=0.43,P＜0.01)and creatinine(r=0.16,P＜0.01).The restricted cubic spline function in the Cox model revealed a significant non-linear relationship between the plasma NLR level and clinical outcomes in AAD patients(P＜0.01).Kaplan-Meier survival analysis indicated that patients in Q4 group had the highest in-hospital mortality rate compared with Q1-Q3 groups(P＜0.0001).Furthermore,multivariate Cox regression analysis demonstrated that compared with Q1 group,the hazard ratio(HR)of NLR in Q4 group was 1.77(95％CI 1.33-2.37,P＜0.001),which was an independent risk factor for the primary endpoint events.Conclusion A higher plasma NLR level is significantly associated with the occurrence of cardiovascular events in AAD patients,and this association remains significant even after adjusting for potential confounding factors such as the multicenter visiting hospitals.

Homeobox(HOX)genes encode a group of proteins that are highly conserved and closely related to the axial differentiation of embryos.The disorder of segmental development caused by HOX genes deficiency or abnormal expression has been observed in drosophila and mice.However,subsequent studies have found that proteins encoded by the HOX gene family are also involved in the regulation of tumor genesis and development.The roles of the whole HOX family had been reviewed by the author in the past,and through the in-depth researches,the author paid attention to the pivotal role of HOXB9 and made new progress in the study of post-translational modifications of this protein.Taking HOXB9 as a clue,this review summarizes the tumor-related signaling pathways and the modulating effects of post-translational modification of HOXB9 on tumor progression,as well as the possible research directions in the future.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective To explore the effect of modified Shaoyao Gancao Decoction combined with acupuncture on Oswestry Disability Index(ODI)of patients after surgery for osteoporotic vertebral compression fracture(OVCF).Methods A total of 94 patients with OVCF of liver-kidney deficiency and yin-blood deficiency type were randomly divided into an observation group and a control group,with 47 cases in each group.Both groups were treated with surgical treatment by percutaneous balloon kyphoplasty or percutaneous vertebroplasty.After the operation,the control group was given acupuncture therapy,and the observation group was treated with modified Shaoyao Gancao Decoction combined with acupuncture therapy.Both groups were treated for 12 weeks(3 months in total).The changes of pain visual analogue scale(VAS)score,ODI score,bone mineral density(BMD)of lumbar vertebrae 2-4(L2-4),femoral neck,Wards triangle and total hip,and serum levels of bone metabolism indicators of type I collagen C-terminal peptide(CTX-1),bone alkaline phosphatase(BALP)and blood calcium in the two groups at different observation time points after operation were observed.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 3 months of treatment,the total effective rate of the observation group was 100.00%(47/47),and that of the control group was 87.23%(41/47).The intergroup comparison(tested by Fisher's exact test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)On the seventh day,first month and third month after operation,the pain VAS score and thoracolumbar function of ODI scores of the two groups were significantly lower than those at the previous observation time point(P＜0.05),and the decrease of VAS score and thoracolumbar ODI score in the observation group was significantly superior to that in the control group on the seventh day,first month and third month after operation(P＜0.05 or P＜0.01).(3)After treatment(one month after operation),the BMD values of L2-4,femoral neck,Wards triangle and total hip in the two groups were significantly higher than those before treatment(P＜0.05),and the increase of BMD values in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment(one month after operation),the serum levels of bone metabolism indicators of CTX-1,BALP and calcium of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of serum CTX-1,BALP and calcium levels in the observation group was significantly superior to that in the control group(P＜0.01).Conclusion Modified Shaoyao Gancao Decoction combined with acupuncture exerts certain effect for the treatment of OVCF patients with liver-kidney deficiency and yin-blood deficiency type.The combined therapy can significantly relieve postoperative pain symptoms,improve BMD and bone metabolism,promote the recovery of thoracolumbar function,and effectively enhance the overall efficacy.

Purpose::Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI.Methods::A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region ( n =21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. Results::In 2019, there were 27.16 million (95% uncertainty intervals ( UI): 23.36 -31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298 -401) and 599 per 100,000 population (95% UI: 573 -627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% --0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% -0.06%). TBI caused 7.08 million (95% UI: 5.00 -9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 -117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. Conclusions::The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.

Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.

This article reports on the clinical and genetic characteristics of monozygotic twins with Marshall-Smith syndrome(MRSHSS)due to a mutation in the NFIX gene,along with a review of related literature.Both patients presented with global developmental delays,a prominent forehead,shallow eye sockets,and pectus excavatum.Genetic testing revealed a heterozygous splicing site mutation c.697+1G>A in both children,with parents showing wild-type at this locus.According to the guidelines of the American College of Medical Genetics and Genomics,this mutation is considered likely pathogenic and has not been previously reported in the literature.A review of the literature identified 32 MRSHSS patients with splicing/frameshift mutations.Accelerated bone maturation and moderate to severe global developmental delay/intellectual disability are the primary clinical manifestations of patients with MRSHSS.Genetic testing results are crucial for the diagnosis of this condition.