Triptolide （TP）， the core active component of the traditional Chinese medicine Tripterygium wilfordii ， exhibits remarkable pharmacological activities including anti-inflammatory， immunosuppressive and anti-tumor effects， and holds broad application prospects in the treatment of major diseases such as autoimmune diseases and malignant tumors. However， TP has a narrow therapeutic window and causes multi-organ toxicities including liver， kidney and reproductive toxicities， which severely restrict its safe clinical application and new drug development. Therefore， toxicity reduction and efficacy enhancement has become a core scientific problem urgently to be solved in this field. This paper systematically reviews the four core strategies for TP toxicity reduction and efficacy enhancement， including structural modification， dosage form improvement， herbal compatibility， and external therapies of traditional Chinese medicine. Among them， structural modification optimizes the toxic and efficacy characteristics of TP from the molecular structure level， with typica l derivatives including （5 R ）-5-hydroxy triptolide， ZT01， PG490-88， etc. Dosage form modification achieves toxicity reduction and efficacy enhancement via targeted and sustained-controlled drug release of diverse delivery systems. It includes triptolide preparations such as nanoparticles， liposomes， microemulsion gels and liquid crystals， possessing favorable clinical transformation potential. The herbal compatibility and external therapies of traditional Chinese medicine conform to the holistic view of traditional Chinese medicine and have a profound clinical application foundation， but their mechanisms of action are insufficiently elucidated， and they lack unified standardized specifications and high-quality evidence-based proof. In the future， we should rely on multi-omics technology to elucidate the toxic and efficacy mechanisms， integrate technologies to optimize preparations， improve the evaluation system and promote clinical transformation.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

The core pathogenesis of childhood IgA vasculitis nephritis （IgAVN） lies in the intermingled conditions of heat， stasis and deficiency. Deficiency is the fundamental cause， while heat acts as the predominant manifestation at the initial stage， and stasis serves as the key factor leading to protracted illness. Based on this understanding， the overall therapeutic principle of clearing heat and cooling blood， dissolving stasis and unblocking collaterals， reinforcing healthy qi and consolidating the root is established. A self-formulated Qingre Zhixue Formula （清热止血方） is used as the basic prescription. According to the characteristics of different disease stages， childhood IgAVN is further classified into three main syndrome types， including blood heat with stasis obstruction， deficiency of both qi and yin， and deficiency of both spleen and kidney， with corresponding syndrome-based treatments. Throughout the treatment process， emphasis is placed on dissolving stasis and unblocking collaterals， while protecting the spleen and stomach of children and maintaining healthy qi. This paper provides new perspectives for diagnosis and treatment of childhood IgAVN with traditional Chinese medicine.

Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.

Protozoan infections(e.g.,malaria,trypanosomiasis,and toxoplasmosis)pose a considerable global burden on public health and socioeconomic problems,leading to high rates of morbidity and mortality.Due to the limited arsenal of effective drugs for these diseases,which are associated with devastating side effects and escalating drug resistance,there is an urgent need for innovative antiprotozoal drugs.The emergence of drug repurposing offers a low-cost approach to discovering new therapies for pro-tozoan diseases.In this review,we summarize recent advances in drug repurposing for various human protozoan diseases and explore cost-effective strategies to identify viable new treatments.We highlight the cross-applicability of repurposed drugs across diverse diseases and harness common chemical motifs to provide new insights into drug design,facilitating the discovery of new antiprotozoal drugs.Chal-lenges and opportunities in the field are discussed,delineating novel directions for ongoing and future research.

Objective To analyze the clinical data of patients with neurosyphilis(NS)and explore factors influencing their activity of daily living(ADL).Methods The clinical data of 90 patients with NS was retrospectively analyzed,and the ADL scores at admission were assessed by using the Barthel index(BI).The patients were divided into no-dependency,mild-dependency,and moderate-to-severe-dependency groups.The influencing factors of ADL were explored through comparative analysis and multiple linear regression analysis.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of clinical indicators for poor ADL recovery(BI score≤60)at discharge in patients.Results Among the 90 NS patients,the average age was 54.17±12.45 years,with 70 males(77.78%).The most common clinical manifestation was abnormal mental behavior(44.44%),followed by limb sensory or motor disorders(25.56%)and dysarthria(16.67%).Based on the BI scores,41 patients(45.6%)were independent,31 patients(34.4%)had mild dependence,and 18 patients(20.0%)had moderate to severe dependence.The comparison results of the three groups showed that the neutrophil-to-lymphocyte ratio(NLR)was gradually increased[2.80(1.97,4.73)vs.3.80(2.28,4.89)vs.5.37(3.76,7.20)]which was higher in the moderate-to-severe-dependency group than in the independent and the mildly-dependent group(P<0.05);cerebrospinal fluid protein concentration[427(341,644)mg/L vs.553(425,830)mg/L vs.933(641,1706.5)mg/L]was gradually increased and there were significant differences in pairwise comparisons(P<0.05).Multiple linear regression analysis showed that NLR(β=-0.242,P=0.018)and cerebrospinal fluid protein concentration(β=-0.461,P<0.001)were negatively correlated with ADL at admission.The area under curve(AUC)for cerebrospinal fluid protein concentration in predicting poor ADL recovery at discharge was 0.806(95%CI:0.708-0.883,P<0.001),with an optimal cutoff value of 620 mg/L,sensitivity of 86.7%,and specificity of 69.4%.Conclusion The main clinical manifestations of NS patients are psychiatric/behavioral abnormalities.Elevated NLR and cerebrospinal fluid protein concentration may be associated with the decreased ADL.Early active intervention of inflammatory response and cerebrospinal fluid protein abnormalities may provide a new way to improve the prognosis of patients.

Objectives:When heparin-induced thrombocytopenia(HIT)is diagnosed before heart transplantation,recommendation varies according to small sample observations from other countries.In China,recent HIT is considered as a relative contradiction for heart transplantation and clinical study results is not yet available.Methods:A total of 325 patients who received heart transplantation in Fuwai Hospital from January 1,2022 to July 31,2024 were retrospectively analyzed,124 of whom received instrumental circulation and heparin before transplantation,and 15 of whom had suspected HIT before surgery.Diagnostic strategy was based on clinical investigation,antibody detection and expert opinion.Results:All 15 patients used intra-aortic balloon pump(IABP)preoperatively,6 were diagnosed with HIT,contributing 4.8%of those who used mechanical circulation support before heart transplantation.Three patients were tested positive for HIT-Ab just before surgery.Three different anticoagulation strategies:bivalirudin,heparin,and combined bivalirudin and heparin was used in each of the 3 patients,respectively.Their clinical features varied significantly.The first patient experienced challenging bleeding issue and cervical vein embolization.The second patient experienced low-limb embolization and the third patient experienced spleen artery embolization.Thrombocyte count returned to normal range at day 8,6 and 10 respectively post operation.Conclusions:HIT is not rare in patients using IABP and other mechanical circulation support devices before heart transplantation.Diagnosis and treatment of HIT is challenging for patients awaiting heart transplantation.

Objective To evaluate the efficacy and safety of different surgical approaches for extracting high-positioned supernumerary teeth in the maxillary anterior midline region.Three surgical methods,the labial approach,the palatal approach,and a longitudinal incision beside the upper lip frenum were compared.Methods A total of 102 patients were recruited from the Department of Oral and Maxillofacial Surgery at the Affiliated Stomatological Hospital of Anhui Medical University between January and September 2024.They were randomly assigned via a random-digit table to three groups:the labial approach group(n=32),the palatal approach group(n=34),and the longitudinal incision beside the upper lip frenum group(n=36).Operation time,bone removal volume,post-operative midfacial swelling,degree of pain,and patient satisfaction across the three groups were recorded and compared.Results The average operation time in the labial approach group((20.50±3.02)min)and the longitudinal incision group((21.66±2.31)min)were both significantly shorter than that in the palatal approach group((29.19±3.40)min).In contrast,the palatal approach group demonstrated markedly lower postoperative swelling and pain scores(P＜0.05),along with the highest patient satisfaction,as reflected in the OHIP-14 scale.However,the palatal approach required the greatest bone removal volume,measuring(91.19±9.86)mm3.Conclusion Despite the palatal approach yielding superior outcomes in terms of postoperative pain control,swelling reduction,and patient satisfaction,it necessitated longer operation time and involved greater bone removal.Meanwhile,the labial approach and the longitudinal incision beside the upper lip frenum were comparable in all measured parameters,showing no statistically significant differences.Therefore,when extracting high midline impacted teeth in the maxillary anterior region,the choice of surgical approach should balance safety,minimal invasiveness,and patient satisfaction.

Objective:To analyze the epidemiological and clinical characteristics of Mycoplasma pneumoniae ( Mp) infection among hospitalized children with acute respiratory tract infections (ARTIs) in a single center in Beijing and provide reference for the prevention and treatment of Mp infection. Methods:Nasopharyngeal aspirate (NPA) samples of hospitalized children with ARTIs were collected from Beijing Friendship Hospital during two periods: from April 2018 to March 2019 and from September 2020 to August 2022. qPCR was used to detect Mp nucleic acids, and for Mp-positive samples, the mixed infections with 15 common respiratory viruses were detected. Statistical analysis was conducted using Chi-square test, Fisher′s exact test, and independent samples t-test. Results:From April 2018 to March 2019, 1 572 NPA samples were collected, with 104 positive for Mp (6.62%). From September 2020 to August 2022, 622 samples were collected, with 22 Mp-positive samples (3.54%). There was statistically significant difference in the positive rates between the two time periods ( P<0.05). From April 2018 to March 2019, the positive rate of Mp was higher in children aged ≥5 years than in those <5 years [13.03% (46/353) vs 4.76% (58/1 219), P<0.05]; the positive rates in summer (9.54%, 35/367) and autumn (7.93%, 33/416) were higher than those in spring (3.03%, 11/363) and winter (5.87%, 25/426), with statistically significant differences ( P<0.05); co-infections with other respiratory viruses were detected in 42 out of the 104 Mp-positive cases (40.38%), primarily with human rhinovirus (35.71%, 15/42) or human coronavirus NL63 (19.05%, 8/42). From September 2020 to August 2022, Mp infections mainly occurred in children aged ≥5 years [72.73% (16/22)], and co-infections with other respiratory viruses were detected in four cases (18.18%, 4/22). The Mp-infected children were mainly diagnosed with pneumonia, and there was no significant difference in clinical symptoms between Mp-infected patients with or without viral coinfection. Conclusions:The positive rate of Mp among hospitalized children with ARTIs in Beijing from September 2020 to August 2022 is significantly lower than that observed from April 2018 to March 2019. Mp is an important cause of ARTIs in children, especially in patients aged ≥5 years. Mp infection is often accompanied by viral co-infections, with high incidence in summer and autumn.

Objective:To analyze the clinical features of postnatal cytomegalovirus (pCMV) infection in very preterm infants or very low birth weight infants.Methods:This was a case-control study. A total of 50 very preterm or very low birth weight infants who were hospitalized and diagnosed with pCMV infection in the Neonatal Intensive Care Unit of Children′s Hospital, Zhejiang University School of Medicine from January 2019 to June 2024, were enrolled as the pCMV group. Meanwhile, through propensity score matching, each infant in the pCMV group was paired with a very preterm or very low birth weight infant without cytomegalovirus infection during the same period, constituting the control group, also consisting of 50 cases. Subsequently, the pCMV group was divided into a treated subgroup and an untreated subgroup according to antiviral treatment. Clinical data of all enrolled infants, including clinical features, laboratory test results, and clinical outcomes were collected. Differences in relevant parameters were analyzed using with χ2 test or continuity-corrected χ2 test or Fisher′s exact test, independent-samples t test, Mann-Whitney U test as appropriate. Logistic regression was employed to analyze the risk factors, and Spearman correlation analysis was applied for non-normal distribution data or ordinal data. Results:There were no significant differences between the pCMV group and the control group in terms of gestational age, birth weight, proportion of male infants, Apgar score at the 1 st minute and 5 th minute and days of breastfeeding during the first 3 weeks of life (all P>0.05). Compared with the control group, the duration of hospital stay and invasive mechanical ventilation were both longer in the pCMV group (both P<0.05). The risks of bronchopulmonary dysplasia, retinopathy of prematurity, and hearing impairment were all higher in the pCMV group when compared with the control group(all P<0.05). The body weight and body length of the infants in the pCMV group were both lower than those of in the control group at the corrected gestational age of 36 weeks (both P<0.05). pCMV infections were associated with the increased incidence of both necrotizing enterocolitis ( OR=11.50, 95% CI 1.94-68.30, P=0.007) and severe intraventricular hemorrhage ( OR=6.82, 95% CI 1.19-38.97, P=0.031) in very preterm infants or very low birth weight infants. In the treated group, the platelet count was significantly improved after 6-8 weeks of antiviral treatment compared with that before treatment ((245±19)×10 9/L vs. (119±14)×10 9/L, t=5.37, P<0.001). Conclusions:Very preterm infants or very low birth weight infants with postnatal cytomegalovirus infection have longer hospital stay and duration of invasive mechanical ventilation, and are highly susceptible to bronchopulmonary dysplasia, retinopathy of prematurity, hearing impairment, and growth restriction. Antiviral treatment can effectively ameliorate thrombocytopenia in these infants.