Case 1: A 19-day-old male infant presented with poor feeding and decreased activity for 2 weeks, worsening with poor responsiveness for 3 days. At 5 days old, he developed poor feeding and poor responsiveness, was hospitalized, and was found to have elevated blood ammonia and thrombocytopenia. Whole-genome genetic analysis revealed a pathogenic homozygous mutation in the PCCA gene, NM-000282.4: c.1834-1835del (p.Arg612AspfsTer44), leading to a diagnosis of propionic acidemia. Case 2: A 4-day-old male infant presented with poor responsiveness and feeding difficulties since birth, with elevated blood ammonia for 1 day. He showed weak sucking and deteriorating responsiveness, with blood ammonia >200 µmol/L. Genetic testing identified two heterozygous mutations in the MMUT gene: NM_000255.4: c.1677-1G>A and NM_000255.4: ex.5del, confirming methylmalonic acidemia. Case 3: A 20-day-old male infant presented with poor feeding for 15 days and skin petechiae for 8 days. He developed feeding difficulties at 5 days old and lower limb petechiae at 12 days old, with blood ammonia measured at 551.6 µmol/L. Genetic analysis found two heterozygous mutations in the PCCA gene: NM_000282.4: c.1118T>A (p.Met373Lys) and NM_000282.4: ex.16-18del, confirming propionic acidemia. In the first two cases, continuous hemodiafiltration was performed for 30 hours and 20 hours, respectively, before administering carglumic acid. In the third case, carglumic acid was administered orally without continuous hemodiafiltration, resulting in a decrease in blood ammonia from 551.6 µmol/L to 72.0 µmol/L within 6 hours, with a reduction rate of approximately 20-25 µmol/(kg·h), similar to the first two cases. Carglumic acid was effective in all three cases, suggesting it may help optimize future treatment protocols for organic acidemia.
Humans ; Male ; Infant, Newborn ; Propionic Acidemia/drug therapy* ; Amino Acid Metabolism, Inborn Errors/genetics* ; Mutation ; Methylmalonyl-CoA Decarboxylase/genetics* ; Citrates/administration & dosage* ; Carbon-Carbon Ligases/genetics* ; Glutamates

Objective:To construct a decision tree model to predict the risk of breast cancer in patients with pathological nipple discharge.Methods:A total of 157 patients with pathological nipple discharge,who were diagnosed and treated at Weifang Municipal Hospital of Traditional Chinese Medicine from January 2019 to April 2024 and met the inclusion criteria,were selected.A risk prediction model for concurrent breast cancer in patients with pathological nipple discharge was developed using Logistic regression analysis.A decision tree was then constructed,and the predictive performance of the model was assessed based on the area under the receiver operating characteristic curve(AUC).Re-sults:The incidence of concurrent breast cancer among patients with pathological nipple discharge was 24.2%.Accord-ing to the results of binary Logistic regression analysis,elevated CEA and CA 153 levels in nipple discharge,as well as bloody discharge,emerged as independent risk factors for the development of breast cancer in such patients(P<0.05).Based on these findings,a decision tree model was constructed to predict the risk of concurrent breast cancer in patients with pathological nipple discharge.The validation results showed that the Logistic regression model had an AUC value of 0.800,while the decision tree model achieved an AUC value of 0.889.Conclusions:The decision tree model,built upon the identified influencing factors,exhibits strong predictive power for the risk of developing concurrent breast can-cer in patients with pathological nipple discharge,thus facilitating more precise preoperative diagnoses by clinicians for these patients.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

This study aimed to explore the pharmacological mechanism of Yourenji Capsules(YRJ) in improving osteoporosis by combining network pharmacology and proteomics technologies. The SD rats were randomly divided into a blank control group and a 700 mg·kg~(-1) YRJ group. The rats were subjected to gavage administration with the corresponding drugs, and the blank serum, drug-containing serum, and YRJ samples were compared using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) to analyze the main components absorbed into blood. Network pharmacology analysis was conducted based on the YRJ components absorbed into blood to obtain related targets of the components and target genes involved in osteoporosis, and Venn diagrams were used to identify the intersection of drug action targets and disease targets. The STRING database was used for protein-protein interaction(PPI) network analysis of potential target proteins to construct a PPI network. Gene Ontology(GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed using Enrichr to investigate the potential mechanism of action of YRJ. Ovariectomy(OVX) was performed to establish a rat model of osteoporosis, and the rats were divided into a sham group, a model group, and a 700 mg·kg~(-1) YRJ group. The rats were given the corresponding drugs by gavage. The femurs of the rats were subjected to label-free proteomics analysis to detect differentially expressed proteins, and GO functional enrichment and KEGG pathway enrichment analyses were performed on the differentially expressed proteins. With the help of network pharmacology and proteomics results, the mechanism by which YRJ improves osteoporosis was predicted. The analysis of the YRJ components absorbed into blood revealed 23 bioactive components of YRJ, and network pharmacology results indicated that key targets involved include tumor necrosis factor(TNF), tumor protein p53(TP53), protein kinase(AKT1), and matrix metalloproteinase 9(MMP9). These targets are mainly involved in osteoclast differentiation, estrogen signaling pathways, and nuclear factor-kappa B(NF-κB) signaling pathways. Additionally, the proteomics analysis highlighted important pathways such as peroxisome proliferator-activated receptor(PPAR) signaling pathways, mitogen-activated protein kinase(MAPK) signaling pathways, and β-alanine metabolism. The combined approaches of network pharmacology and proteomics have revealed that the mechanism by which YRJ improves osteoporosis may be closely related to the regulation of inflammation, osteoblast, and osteoclast metabolic pathways. The main pathways involved include the NF-κB signaling pathways, MAPK signaling pathways, and PPAR signaling pathways, among others.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Osteoporosis/metabolism* ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Female ; Protein Interaction Maps/drug effects* ; Capsules ; Humans ; Signal Transduction/drug effects*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To construct a decision tree model to predict the risk of breast cancer in patients with pathological nipple discharge.Methods:A total of 157 patients with pathological nipple discharge,who were diagnosed and treated at Weifang Municipal Hospital of Traditional Chinese Medicine from January 2019 to April 2024 and met the inclusion criteria,were selected.A risk prediction model for concurrent breast cancer in patients with pathological nipple discharge was developed using Logistic regression analysis.A decision tree was then constructed,and the predictive performance of the model was assessed based on the area under the receiver operating characteristic curve(AUC).Re-sults:The incidence of concurrent breast cancer among patients with pathological nipple discharge was 24.2%.Accord-ing to the results of binary Logistic regression analysis,elevated CEA and CA 153 levels in nipple discharge,as well as bloody discharge,emerged as independent risk factors for the development of breast cancer in such patients(P<0.05).Based on these findings,a decision tree model was constructed to predict the risk of concurrent breast cancer in patients with pathological nipple discharge.The validation results showed that the Logistic regression model had an AUC value of 0.800,while the decision tree model achieved an AUC value of 0.889.Conclusions:The decision tree model,built upon the identified influencing factors,exhibits strong predictive power for the risk of developing concurrent breast can-cer in patients with pathological nipple discharge,thus facilitating more precise preoperative diagnoses by clinicians for these patients.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4％)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P＜0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P＜0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P＜0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P＜0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P＞0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P＜0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P＜0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Objective:To explore the genotypes and frequency distribution of thalassemia in Lingui District,Guilin City,and provide reference for the prevention and control of thalassemia in this area. Methods:The results of genetic testing for thalassemia in 1501 suspected cases at the Second Affiliated Hospital of Guilin Medical University were analyzed retrospectively. The deletional mutations of α-thalassemia were detected by gap-PCR,the non-deletional mutations of α-thalassemia and β-thalassemia mutations were detected by PCR-reverse dot blot (PCR-RDB). Results:In 1501 samples,a total of 678 cases of thalassemia carriers were detected,with a detection rate of 45.17％. Among them,379 cases were α-thalassemia (including deletional α-thalassemia and non-deletional α-thalassemia),with a detection rate of 25.25％,the most common genotype was--SEA/αα (227 cases,15.12％),followed by-α3.7/αα (53 cases,3.53％). 270 cases of β-thalassemia were detected,with a detction rate of 17.99％,and βCD41-42/βN (144 cases,9.59％) was the main genotypes,followed by βCD17/βN (66 cases,4.40％) . In addition,there were 29 cases of αβ compound thalassemia,accounting for 1.93％,and the most common genotype was--SEA/αα complex βCD41-42/βN (5 cases,0.33％). Conclusion:Lingui District in Guilin City is a high-incidence area of thalassemia,and the genotypes of carriers are complex and diverse,with genetic heterogeneity. The results of this study provide a scientific basis for genetic counseling and prenatal diagnosis in this area.