Accurate identification of endogenous and exogenous substances in food,particularly in competition supplies,is crucial for ensuring food safety and fair competition,as well as for protecting the legitimate rights and professional reputations of athletes.Testosterone(T)and dehydroepiandrosterone(DHEA)are important steroid hormones that can stimulate protein synthesis,increase the number and volume of muscle cells,and promote muscle growth and recovery.Both are often illegally used in the animal husbandry industry to promote animal growth and improve meat quality.However,current research in this area remains limited,and identification technologies require further investigation.This study focused on the techniques for identifying endogenous and exogenous hormones including T and DHEA in beef.A Soxhlet extraction method was established,reducing the pretreatment cycle to 110 min while achieving high extraction efficiency,with recovery rates of 102.5%for T and 91.9%for DHEA,respectively.Based on this,a gas chromatography-combustion-isotope ratio mass spectrometry(GC-C-IRMS)method was developed for analyzing carbon isotopes in T and DHEA,eliminating the need for derivatization.By adding reference materials to the extract,simultaneous measurement of reference materials and target analytes was achieved.The measurement of caffeine reference material,T and DHEA was completed within 40 min,with a measurement repeatability of 0.02‰.Theδ13C values of T and DHEA in standard substances,which may serve as exogenous additives,were determined using elemental analysis-isotope ratio mass spectrometry(EA-IRMS).The results indicated an average δ13C value of-29.44‰±0.81‰(k=1)for 10 T standards and-30.86‰±0.87‰(k=1)for 14 kinds of DHEA standards.This approach effectively distinguished between endogenous sources and exogenous addition of these two hormones in beef,thereby providing vital technical support for the assurance and supervision of food safety.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature

Objective:To investigate the patterns of mutation evolution in patients with acute myeloid leukemia (AML) during treatment and the possible clinical significances.Methods:A retrospective case series study was conducted. A total of 103 AML patients who were hospitalized at the Affiliated Yuebei People's Hospital of Medical College of Shantou University from November 2019 to August 2021 and underwent high-throughput next-generation sequencing (NGS) technology to detect the mutations of 128 AML-related genes in bone marrow samples were selected. Based on the NGS results, the somatic gene mutations in samples of patients collected at initial diagnosis (73 cases), complete remission (CR) (30 cases), non-remission (NR) (23 cases), and recurrence (12 cases) were analyzed, and the targeted drugs involved in the gene mutations detected in NR and recurrence samples were summarized.Results:The median age [ M ( Q1, Q3)] of onset for 103 patients was 58 (48, 66) years, including 64 males (61%) and 39 females (39%); 86 cases (83%) were primary AML, and 17 cases (17%) were secondary AML; at the initial diagnosis, 51 cases (50%) had normal karyotypes, 34 cases (33%) had abnormalities, and 18 cases (17.5%) were unknown. Compared with the CR samples, the mutation frequencies of FLT3 [29% (21/73) vs. 3% (1/30)], NPM1 [27% (20/73) vs. 3% (1/30)], NRAS [22% (16/73) vs. 3% (1/30)], and IDH2 [14% (10/73) vs. 0 (0/30)] were all higher in the initial diagnosis samples, and the differences were statistically significant (all P < 0.05); compared with the initial diagnosis sample, the median number of gene mutations in each CR sample was lower [4 (2, 5) vs. 7 (5, 9)], and the difference was statistically significant ( P < 0.001). However, there was no statistically significant difference in the median number of gene mutations in each patient between the initial diagnosis samples and the NR samples, the initial diagnosis samples and the recurrence samples, and the NR samples and the recurrence samples (all P > 0.05). Analysis of 14 patients with NGS data at initial diagnosis and CR showed that the same gene mutations could be detected at initial diagnosis and CR, such as DNAH23 (3 cases), USH2A (3 cases), etc; partial gene mutations were detected at initial diagnosis but were not detected at CR, including NRAS (5 cases), FLT3 (3 cases), ANKRD26 (3 cases), NPM1 (3 cases), ETV6 (3 cases), etc; ARID1B (1 case) and DNMT3A (1 case) were negative for mutations at initial diagnosis but positive upon reaching CR. Analysis of 14 patients with NGS data at initial diagnosis and NR showed that most gene mutations persisted at initial diagnosis and NR, such as DNMT3A (5 cases), NRAS (5 cases), KRAS (3 cases), RUNX1 (3 cases), etc; the mutant genes detected at initial diagnosis but not detected at NR included USH2A (2 cases), PCLO (2 cases), ATM (2 cases), FAT1 (2 cases), etc; partial gene mutations were not detected at initial diagnosis but were detected at NR, such as FAT1 (2 cases), TCF3 (2 cases), etc. Analysis of 5 patients with NGS data at CR and recurrence showed that some gene mutations were detected at both CR and recurrence, such as BCORL1 (1 case), ARID2 (1 case), SETD2 (1 case), VEGFC (1 case), etc; FLT1 (1 case) and GNAS (1 case) gene mutations were detected at CR but not detected at recurrence; at recurrence, some gene mutations that were not detected at CR were also detected, such as ANKRD26 (1 case), WT1 (1 case), etc. Among the 23 NR samples and 12 recurrence samples, the targets of drugs approved by US Food and Drug Administration or in clinical trials were detected in 14 (61%) and 5 (42%) samples respectively, including IDH1, IDH2, FLT3, KIT, KRAS, NRAS, SF3B1, U2AF1, and SRSF2. Conclusions:The number of gene mutations in AML patients during CR is significantly less than that at initial diagnosis, some gene mutations disappear when CR is achieved through treatment, but the majority of gene mutations persist during the treatment period, including NR and recurrence, suggesting that monitoring through NGS technology can help understand the evolution of gene mutations during AML treatment and discover the potential therapeutic targets.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

Objective To evaluate the clinical outcomes of 514 cases of anterior cruciate ligament(ACL)reconstruction using hamstring tendon autograft and to observe postoperative changes and recovery of the grafts through second-look arthroscopy.Methods This retrospective study collected data from 514 patients who underwent ACL reconstruction with hamstring tendon autograft between May 2015 and June 2018,with a follow-up of at least one year.Knee function recovery and stability were assessed using the Lysholm score,International Knee Documentation Committee(IKDC)score,and Tegner score,along with the pivot shift test and Lachman test.During the second-look arthroscopy,key observations included the synovial coverage,continuity of the reconstructed ligament,and any intra-articular abnormalities.Results The time interval between ACL reconstruction and second-look arthroscopy ranged from 12 to 28 months,with an average of 20 months.Postoperative infection occurred in 2 cases,both of which were successfully treated with arthroscopic debridement and drainage.No other patients experienced infections,graft resorption,or other complications.At the second-look arthroscopy,the Lysholm score significantly improved from(43.56±9.89)preoperative to(92.21±6.12)postoperatively,the difference was statistically significant(P<0.05);The IKDC score increased from(20.32±7.87)to(85.67±10.43),the difference was statistically significant(P<0.05);The Tegner score improved from(4.31±0.82)to(6.61±1.21),the difference was statistically significant(P<0.05).Second-look arthroscopy revealed that the ligament remained intact in 375 patients,with partial tears in 139 patients,ligament tension was maintained in 447 patients,while 67 patients had laxity,the reconstructed ACL graft was deemed to be in good condition in 435 patients and suboptimal in 79 patients,there were significant differences observed in pre-and post-pivot shift test and Lachman test(P<0.05);Among the 514 patients,188(36.58%)successfully returned to sport.Conclusion ACL reconstruction using hamstring tendon autograft effectively restores knee function and stability.In patients followed for more than one years,the grafts show good vascularization and synovial coverage.Emphasis should be placed on systematic postoperative rehabilitation to optimize recovery.

Objective To explore the clinical efficacy and safety of alendronate sodium tablet combined with injection of recombinant teriparatide and calcium carbonate D3 tablet in the treatment of postmenopausal osteoporosis(PMDP).Methods The patients with postmenopausal osteoporosis were divided into control group and treatment group according to the cohort method according to the treatment regimen.The control group was treated with calcium carbonate D3 tablet(600 mg,1 tablet a day)and alendronate sodium tablet(70 mg,once a week),while the treatment group was given injection of reacombinant teriparatide(200 U/20 μg,20 μg every day)on the basis of the control group.Both groups were continuously treated for 6 months.The clinical efficacy was compared after 6 months of treatment.The bone mineral density(BMD)of lumbar spine,total hip and femoral neck and levels of bone metabolism indicators[osteocalcin(OCN),tartrate-resistant acid phosphatase-5b(TRAP-5b),procollagen type Ⅰ amino-terminal propeptide(PINP),C-terminal cross-linked peptide of type Ⅰ collagen(CTX-Ⅰ)]before treatment and after 6 months of treatment and bone pain[visual analogue scale(VAS)]and quality of life[European Foundation Osteoporosis Quality of Life Questionnaire(ECOS-16)]before treatment and after 3 and 6 months of treatment were recorded,and the adverse drug reactions within 6 months of treatment were compared.Results Fifty-two cases in treatment group and 64 cases in control group were enrolled.After treatment,the total effective rates in treatment group and control group were 87.80％(36 cases/41 cases)and 68.29％(28 cases/41 cases),respectively(P＜0.05).The BMD values of lumbar spine in treatment group and control group after treatment were(0.69±0.15)and(0.79±0.18)g·cm-2;the BMD values of total hip were(0.70±0.11)and(0.77±0.15)g·cm-2;the BMD values of femoral neck were(0.79±0.19)and(0.87±0.15)g·cm-2,respectively;the OCN levels were(7.42±1.53)and(5.37±1.16)μg·L-1;the PINP levels were(85.31±5.66)and(76.30±5.49)ng·mL-1;the TRAP-5b levels were(3.27±0.46)and(5.16±0.72)U·L-1;the CTX-Ⅰ levels were(3.37±0.54)and(5.08±0.70)ng·mL-1;the VAS scores were(1.48±0.13)and(2.07±0.24)points;the ECOS-16 scores were(24.84±4.62)and(32.71±6.07)points,and there were statistical differences in the above indicators between treatment group and control group(all P＜0.05).The main adverse drug reactions in treatment group were rash,dizziness and limb pain,and the main adverse drug reactions in control group were rash,dizziness,nausea,and limb pain,and the total incidence rates of adverse reactions in treatment group and control group were 12.20％(5 cases/41 cases)and 19.51％(8 cases/41 cases)(P＞0.05).Conclusion Alendronate sodium tablet combined with injection of recombinant teriparatide and calcium carbonate D3 tablet has a significant short-term efficacy on PMOP patients,and it can help to enhance the bone mineral density,reduce the symptoms of bone pain,and relieve the osteoporosis.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Objective To explore the clinical efficacy and safety of alendronate sodium tablet combined with injection of recombinant teriparatide and calcium carbonate D3 tablet in the treatment of postmenopausal osteoporosis(PMDP).Methods The patients with postmenopausal osteoporosis were divided into control group and treatment group according to the cohort method according to the treatment regimen.The control group was treated with calcium carbonate D3 tablet(600 mg,1 tablet a day)and alendronate sodium tablet(70 mg,once a week),while the treatment group was given injection of reacombinant teriparatide(200 U/20 μg,20 μg every day)on the basis of the control group.Both groups were continuously treated for 6 months.The clinical efficacy was compared after 6 months of treatment.The bone mineral density(BMD)of lumbar spine,total hip and femoral neck and levels of bone metabolism indicators[osteocalcin(OCN),tartrate-resistant acid phosphatase-5b(TRAP-5b),procollagen type Ⅰ amino-terminal propeptide(PINP),C-terminal cross-linked peptide of type Ⅰ collagen(CTX-Ⅰ)]before treatment and after 6 months of treatment and bone pain[visual analogue scale(VAS)]and quality of life[European Foundation Osteoporosis Quality of Life Questionnaire(ECOS-16)]before treatment and after 3 and 6 months of treatment were recorded,and the adverse drug reactions within 6 months of treatment were compared.Results Fifty-two cases in treatment group and 64 cases in control group were enrolled.After treatment,the total effective rates in treatment group and control group were 87.80％(36 cases/41 cases)and 68.29％(28 cases/41 cases),respectively(P＜0.05).The BMD values of lumbar spine in treatment group and control group after treatment were(0.69±0.15)and(0.79±0.18)g·cm-2;the BMD values of total hip were(0.70±0.11)and(0.77±0.15)g·cm-2;the BMD values of femoral neck were(0.79±0.19)and(0.87±0.15)g·cm-2,respectively;the OCN levels were(7.42±1.53)and(5.37±1.16)μg·L-1;the PINP levels were(85.31±5.66)and(76.30±5.49)ng·mL-1;the TRAP-5b levels were(3.27±0.46)and(5.16±0.72)U·L-1;the CTX-Ⅰ levels were(3.37±0.54)and(5.08±0.70)ng·mL-1;the VAS scores were(1.48±0.13)and(2.07±0.24)points;the ECOS-16 scores were(24.84±4.62)and(32.71±6.07)points,and there were statistical differences in the above indicators between treatment group and control group(all P＜0.05).The main adverse drug reactions in treatment group were rash,dizziness and limb pain,and the main adverse drug reactions in control group were rash,dizziness,nausea,and limb pain,and the total incidence rates of adverse reactions in treatment group and control group were 12.20％(5 cases/41 cases)and 19.51％(8 cases/41 cases)(P＞0.05).Conclusion Alendronate sodium tablet combined with injection of recombinant teriparatide and calcium carbonate D3 tablet has a significant short-term efficacy on PMOP patients,and it can help to enhance the bone mineral density,reduce the symptoms of bone pain,and relieve the osteoporosis.