OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics. Our endeavor involved the implementation of a bioisosterism strategy, leading to the discovery of an assemblage of halogen-containing biphenyl-diarylpyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Notably, compound A12 demonstrated exceptional efficacy against both WT HIV-1 (EC₅₀ = 1.9 nmol/L) and seven mutant strains (EC₅₀ = 1.7-157 nmol/L), surpassing that of the lead compound 6 and comparable to etravirine. Furthermore, this analog exhibited minimal adverse effects with significantly reduced cytotoxicity (CC₅₀ = 195 μmol/L) and a high selectivity index (SI = 102,608), superior to those of etravirine (CC₅₀ > 4.6 μmol/L, SI > 1436) and rilpivirine (CC₅₀ = 3.98 μmol/L, SI = 3989). It displayed low inhibition of CYP (IC₅₀ = 6.99-25 μmol/L) and hERG (IC₅₀ > 40 μmol/L), indicating a safer profile compared to etravirine and rilpivirine. No acute toxicity or organ pathological damage was observed at a single dose of 2 g/kg. Additionally, A12 exhibited favorable oral bioavailability (F = 29.2%) and an extended elimination half-life (T _1/2 = 13.56 h), enabling convenient oral administration at minimal doses. These findings indicated that A12 could serve as a promising drug candidate for HIV treatment.

Objective    To investigate the radiomics features to distinguish invasive lung adenocarcinoma with micropapillary or solid structure. Methods    A retrospective analysis was conducted on patients who received surgeries and pathologically confirmed invasive lung adenocarcinoma in our hospital from April 2016 to August 2019. The dataset was randomly divided into a training set [including a micropapillary/solid structure positive group (positive group) and a micropapillary/solid structure negative group (negative group)] and a testing set (including a positive group and a negative group) with a ratio of 7∶3. Two radiologists drew regions of interest on preoperative high-resolution CT images to extract radiomics features. Before analysis, the intraclass correlation coefficient was used to determine the stable features, and the training set data were balanced using synthetic minority oversampling technique. After mean normalization processing, further radiomics features selection was conducted using the least absolute shrinkage and selection operator algorithm, and a 5-fold cross validation was performed. Receiver operating characteristic (ROC) curves were depicted on the training and testing sets to evaluate the diagnostic performance of the radiomics model. Results    A total of 340 patients were enrolled, including 178 males and 162 females with an average age of 60.31±6.69 years. There were 238 patients in the training set, including 120 patients in the positive group and 118 patients in the negative group. There were 102 patients in the testing set, including 52 patients in the positive group and 50 patients in the negative group. The radiomics model contained 107 features, with the final 2 features selected for the radiomics model, that is, Original_ glszm_ SizeZoneNonUniformityNormalized and Original_ shape_ SurfaceVolumeRatio. The areas under the ROC curve of the training and the testing sets of the radiomics model were 0.863 (95%CI 0.815-0.912) and 0.857 (95%CI 0.783-0.932), respectively. The sensitivity was 91.7% and 73.7%, the specificity was 78.8% and 84.0%, and the accuracy was 85.3% and 78.4%, respectively. Conclusion    There are differences in radiomics features between invasive pulmonary adenocarcinoma with or without micropapillary and solid structures, and the radiomics model is demonstrated to be with good diagnostic value.

Objective To evaluate the bioequivalence and safety of ibuprofen arginine granules test and reference formulations in Chinese healthy volunteers under fasting and postprandial conditions,and to provide evidence for consistency evaluation and clinical application of the drugs.Methods A single-center,single-dose,randomized,open-label,fasting and postprandial,two-period,two-crossover trial design was used.Twenty-four healthy Chinese volunteers were enrolled in the fasting and postprandial trial,respectively.The test preparation and reference preparation of ibuprofen arginine granules 0.4 g were taken orally in a randomized crossover single dose.Data analysis was performed using Phoenix WinNonlin 8.3.Results In the fasting group,the main pharmacokinetic parameters of ibuprofen in plasma after administration of the test and reference formulations of ibuprofen arginine granules were as follows:Cmax were(51.07±7.43)and(50.10±7.64)μg·mL-1;AUC0-,were(122.78±20.62)and(119.94±21.03)μg·h·mL-1;AUC0_∞ were(125.84±21.31)and(122.64±21.87)μg·h·mL-1,respectively.In the postprandial group,the main pharmacokinetic parameters of ibuprofen in plasma after administration of the test and reference formulations of ibuprofen arginine granules were as follows:Cmax were(17.47±3.56)and(17.89±4.47)μg·mL-1;AUC0-twere(114.33±17.12)and(122.13±29.46)μg·h·mL-1;AUC0_∞ were(134.04±36.72)and(133.96±30.35)μg·h·mL-1,respectively.The 90％confidence intervals of the geometric mean ratio of the two preparations were as follows:Cmax 97.96％-106.02％,AUC0_t 98.77％-105.14％,AUC0-∞ 99.34％-105.19％in fasting group;in postprandial group,Cmax was 92.37％-103.05％,AUC0-t was 93.31％-99.56％,AUC0-∞ was 93.89％-102.91％.Conclusion The test preparation and reference preparation of ibuprofen arginine granules in this study are bioequivalent in healthy adult Chinese volunteers.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) infection posed a huge threat and burden to public healthcare in late 2022. Non-drug measures of traditional Chinese medicine (TCM), such as acupuncture, cupping and moxibustion, are commonly used as adjuncts in China to help in severe cases, but their effects remain unclear. OBJECTIVES: To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was designed as a multicenter, assessor-blind, randomized controlled trial. Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group. The treatment group received individualized TCM non-drug measures in combination with prone position ventilation, while the control group received prone position ventilation only for 5 consecutive days. MAIN OUTCOME MEASURES: The primary outcome measures were the percentage of patients with improved oxygen saturation (SpO₂) at the end of the 5-day intervention, as well as changes of patients' respiratory rates. The secondary outcome measures included changes in SpO₂ and total score on the self-made respiratory symptom scale. The improvement rate, defined as a 3-day consecutive increase in SpO₂, the duration of prone positioning, and adverse events were recorded as well. RESULTS: Among the 198 patients included in the intention-to-treat analysis, 159 (80.3%) completed all assessments on day 5, and 39 (19.7%) patients withdrew from the study. At the end of the intervention, 71 (91%) patients in the treatment group had SpO₂ above 93%, while 61 (75.3%) in the control group reached this level. The proportion of participant with improved SpO₂ was significantly greater in the intervention group (mean difference [MD] = 15.7; 95% confidence interval [CI]: 4.4, 27.1; P = 0.008). Compared to the baseline, with daily treatment there were significant daily decreases in respiratory rates in both groups, but no statistical differences between groups were found (all P ≥ 0.05). Compared to the control group, the respiratory-related symptoms score was lower among patients in the treatment group (MD = -1.7; 95% CI: -2.8, -0.5; P = 0.008) after day 3 of treatment. A gradual decrease in the total scores of both groups was also observed. Thirty-one adverse events occurred during the intervention, and 2 patients were transferred to the intensive care unit due to deterioration of their illness. CONCLUSION: TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19. The combined therapy significantly increased SpO₂ and improved symptom scores compared to prone positioning alone, thus improving the patients' respiratory function to help them recover. However, the improvement rate did not differ between the two groups. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR2300068319). Please cite this article as: Yin X, Jin Z, Li F, Huang L, Hu YM, Zhu BC, Wang ZQ, Li XY, Li JP, Lao LX, Mi YQ, Xu SF. Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial. J Integr Med. 2024; 22(6): 637-644.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Acupuncture Therapy/methods* ; China ; COVID-19/complications* ; Medicine, Chinese Traditional/methods* ; Moxibustion/methods* ; Oxygen Saturation ; Prone Position ; Respiration, Artificial ; Treatment Outcome

The resin ethanol extract of Gegen Qinlian Decoction(GGQLD) has been found to significantly alleviate the intestinal toxicity caused by Irinotecan, but further research is needed to establish its overall quality and clinical medication standards. This study aimed to establish an HPLC characteristic fingerprint of the resin ethanol extract of GGQLD, predicted the targets and signaling pathways of its pharmacological effects based on network pharmacology, identified core compounds with pharmacological relevance, and analyzed potential quality markers(Q-markers) of the resin eluate of GGQLD for relieving Irinotecan-induced toxicity. By considering the uniqueness, measurability, and traceability of Q-markers based on the "five principles" of Q-markers and combining them with network pharmacology techniques, the overall efficacy of the resin ethanol extract of GGQLD can be characterized. Preliminary predictions suggested that the four components of puerarin, berberine, baicalin, and baicalein might serve as potential Q-markers for the resin etha-nol extract of GGQLD. This study provides a basis and references for the quality control and clinical mechanism of the resin ethanol extract of GGQLD.
Irinotecan ; Network Pharmacology ; Drugs, Chinese Herbal/therapeutic use*

italic>Astragalus is a commonly used Chinese medicinal material in traditional Chinese medicine (TCM), and with the increase of planting area in recent years, the damage of Astragalus root rot has worsened year by year, which seriously affecting its quality and yield. Fusarium oxysporum is one of the main pathogens causing root rot in astragalus. In this study, UPLC-Q-TOF-MS based metabolomic approach combined with multivariate statistical analysis were used to analyze the metabolite changes of Astragalus in response to F. oxysporum infection. The results showed that 62 metabolites in the Astragalus had significant changes after inoculation of F. oxysporum. Polar metabolites included 40 flavonoids, 8 saponins, 2 nucleosides, 1 vitamin, 1 organic acid, 1 amino acid; while lipid metabolites included 3 fatty acids, 1 diradylglycerols, 2 lysophosphatidylcholine, 1 lysophosphatidylglycerol, 1 phosphatidylinositol, 1 sterol lipid. Among these differential metabolites, the relative content of flavonoids, vitamin B₂, tryptophan and salicylic acid were increased, while the relative content of saponins were decreased. Correlation analysis showed that the flavonoids were positively correlated with each other, and positively correlated with most lipids, but negatively correlated with most saponins. In addition, studies have shown that F. oxysporum infection is not an influencing factor for the generation of malonyl substitution of flavonoid. This study elucidates the effect of F. oxysporum infection on Astragalus from the perspective of plant metabolism, which provides a basis for exploring the interaction mechanism between the Astragalus and F. oxysporum and further promoting molecular breeding.

Abstract: Objective　To evaluate the potential transmission risk of schistosomiasis in Yunnan Province, and to provide strategic basis for the prevention and control. Methods　Based on the prevalence of schistosomiasis, the social and environmental factors that may lead to the epidemic, 1-3 villages from 3 provincial-level and 15 county-level counties (cities and districts) were selected as the evaluated villages in 2021. The risk of schistosomiasis spread was analyzed comprehensively by consulting, reviewing and collecting routine surveillance data of schistosomiasis in the villages, combined with snail and wild feces survey. The risk level was evaluated for the positive snails, positive wild feces, resident infection, average density of live snails and snail frame occurrence rate. Results　Totally 7 snail counties schistosomiasis transmission was blocked of 18 epidemic counties and the rest were eliminated counties. A total of 152 447 snail frames were investigated and 3 043 frames with snails, 15 895 snails were captured and included 15 727 live snails in the 32 evaluated villages. The total area of snail was 58.87 hm2 and the area of reoccurrence was 34.19 hm2 with snail frame occurrence rate of 2.00% and average density of live snails 0.103 2/0.11 m2, and no positive snails were found by loop-mediated isothermal amplification (LAMP) assay. A total of 1 374 wild feces were collected in 27 evaluated villages of 14 epidemic counties, mainly from cattle, dogs, sheep, equine animals, pigs and so on, all of which were negative. According to the risk assessment of epidemic spread, Yongle Village and Yongsheng Village in Eryuan County, Zhiming Village in Chuxiong City were Ⅱ risk, and the rest were Ⅲ risk. Conclusions　Although the risk of transmission is low in Yunnan Province, the risk of transmission and spread still exists. It is necessary to strengthen the risk monitoring, control of snail and effective management of livestock to prevent the rebound of the epidemic.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.
Humans ; Retrospective Studies ; Esophageal Neoplasms/pathology* ; Carcinoma/drug therapy* ; Prognosis ; Treatment Outcome ; Chemoradiotherapy/methods* ; Radiotherapy Dosage