ObjectiveTo investigate the potential therapeutic effects of Dengzhan Shengmai capsules （DZSM） on myocardial fibrosis after myocardial infarction and decipher the underlying molecular mechanisms by virtue of network robustness algorithm. MethodsA rat model of myocardial infarction was established by ligating the left anterior descending coronary artery. Successfully modeled Sprague-Dawley rats were randomly allocated into a model group， an enalapril group（3.15 mg·kg^-1）， and high- and low-dose DZSM groups（226.8，113.4 mg·kg^-1）. In addition， a sham group was set up. After four consecutive weeks of intervention， the cardiac function was assessed via echocardiography， and myocardial collagen deposition was observed through Sirius red staining. The key regulatory pathways of DZSM were analyzed by the network robustness algorithm. Enzyme-linked immunosorbent assay （ELISA） and immunofluorescence assay were employed to validate the mechanisms. ResultsCompared with the sham group， the model group exhibited decreased left ventricular ejection fraction （LVEF%） and fractional shortening （FS%） （P<0.01） and increased myocardial collagen volume fraction （CVF%） （P<0.01）. Compared with the model group， high-dose DZSM and enalapril improved LVEF% and FS% （P<0.01）. Both high- and low-dose DZSM reduced the CVF% （P<0.05， P<0.05，）. Network analysis indicated that DZSM exerted its effects by regulating neutrophil infiltration and related inflammatory pathways. Experimental validation showed that DZSM significantly reduced the protein levels of nuclear factor （NF）-κB， Janus kinase 2 （JAK2）， and signal transduction activator and transducer 3 （STAT3） in the cardiac tissue， as well as the levels of chemokine （C-X-C motif） ligand 1 （CXCL1）， interleukin （IL）-1β， neutrophil elastase-DNA complex （NE-DNA）， and myeloperoxidase-DNA complex （MPO-DNA） in the plasma. ConclusionDZSM may ameliorate myocardial fibrosis by inhibiting neutrophil infiltration and extracellular trap formation and regulating the NF-κB/JAK2/STAT3 signaling pathway.

Objective To develop predictive models based on decision tree and logistic regression algo-rithms for pulmonary multidrug-resistant organism(MDRO)infection risk in intensive care unit(ICU)pa-tients,and compare their predictive performance to provide references for pulmonary MDRO infection preven-tion.Methods A total of 350 ICU patients admitted to the hospital from January 2021 to December 2023 were enrolled and divided into an infection group(n=52)and a non-infection group(n=298)based on the pres-ence of pulmonary MDRO infection.Clinical data from both groups were collected and analyzed to identify risk factors for pulmonary MDRO infection in ICU patients.Using the risk of pulmonary MDRO infection in ICU patients as the dependent variable and the indicators with statistically significant differences in univariate anal-ysis as the independent variables,predictive models for pulmonary MDRO infection risk were developed by u-sing decision tree algorithms and logistic regression analysis.The predictive performance of these two models was compared.Results There were statistically significant differences(P＜0.05)between the infection and non-infection groups in terms of age,history of diabetes,hospital stay≥2 weeks,indwelling urinary catheter,chlorine dioxide disinfection,prolonged bedridden status,and disturbance of consciousness.Logistic regression analysis with pulmonary MDRO infection risk in ICU patients as the dependent variable showed that age ≥60 years,indwelling catheter,hypoproteinemia,and disturbance of consciousness were risk factors for pulmonary MDRO infection in ICU patients,while chlorine dioxide disinfection was a protective factor.Based on these risk factors and regression coefficients,the original warning model was established as:logit(P 1)=0.856 × age+0.928 × indwelling catheter+0.916 × chlorine dioxide disinfection+0.866× hypoproteinemia+0.986 × disturbance of consciousness-4.371.The Hosmer-Lemeshow test indicated good model fit(coefficient of de-termination R2=0.579,P=0.531).The decision tree model for pulmonary MDRO infection risk in ICU pa-tients constructed using decision tree algorithm comprised 4 layers and 9 nodes,selecting four clinical features as nodes:presence of consciousness disturbance,indwelling catheter,hypoproteinemia,and age≥60 years,with consciousness disturbance being the most significant predictor.The decision tree model showed an area under the curve(AUC)of 0.892(95％CI:0.835-0.949)on receiver operating characteristic(ROC)analy-sis,compared to 0.862(95％CI:0.812-0.912)for the logistic regression model.Delong test revealed no sig-nificant difference in predictive performance between the two models(Z=1.148,P=0.095).Conclusion Both the decision tree model and logistic regression model established for predicting the risk of pulmonary MDRO infection in ICU patients demonstrate high predictive performance with comparable efficacy.

In the field of substance detection,ion dissociation techniques have become crucial for enhancing qualitative accuracy.By applying external energy to induce dissociation of ions in the substance being analyzed,the internal structural information can be obtained,thereby improving qualitative capabilities.Current research on ion dissociation techniques primarily focuses on tandem mass spectrometry,which typically requires a vacuum environment.However,research on ambient ion dissociation techniques is less developed,with some progress made in the field of tandem ion mobility spectrometry.Recently,the development of field-induced dissociation(FID)in this area has enabled ambient dissociation of various explosive and volatile alcohol ions.Nevertheless,the limitation imposed by the maximum breakdown field of air restricts the energy of the electric field,making it challenging to dissociate ions with high energy requirements,such as those of drugs.To address this issue,in this work,an ambient heat-induced dissociation(HID)technique based on high temperatures was proposed,in which an ambient ion heat-induced dissociation unit was developed and integrated into a home-made ion trap mass spectrometer.Experiments were conducted on four representative drug samples,e.g.methamphetamine,heroin,cocaine,and ketamine.The parent ions mass spectra,low vacuum collision-induced dissociation(CID)mass spectra and ambient HID mass spectra for each sample were obtained.By analyzing and comparing the fragmentation products from ambient and low vacuum dissociation,the feasibility of the ambient HID technique was verified.This technique provided a method for ion dissociation in single mass analyzers without tandem mass spectrometry capability and offered a new research direction for the future development of tandem ion mobility spectrometry.

Ureaplasma urealyticum (UU) is one of the most commonly occurring pathogens associated with genital tract infections in infertile males, but the impact of seminal UU infection in semen on intrauterine insemination (IUI) outcomes is poorly understood. We collected data from 245 infertile couples who underwent IUI at The First Affiliated Hospital of USTC (Hefei, China) between January 2021 and January 2023. The subjects were classified into two groups according to their UU infection status: the UU-positive group and the UU-negative group. We compared semen parameters, pregnancy outcomes, and neonatal birth outcomes to investigate the impact of UU infection on IUI outcomes. There were no significantly statistical differences in various semen parameters, including semen volume, sperm concentration, total and progressive motility, sperm morphology, leukocyte count, the presence of anti-sperm antibody, and sperm DNA fragmentation index (DFI), between the UU-positive and UU-negative groups of male infertile patients (all P > 0.05). However, the high DNA stainability (HDS) status of sperm differed between the UU-positive and UU-negative groups, suggesting that seminal UU infection may affect sperm nuclear maturation ( P = 0.04). Additionally, there were no significant differences in pregnancy or neonatal birth outcomes between the two groups (all P > 0.05). These results suggest that IUI remains a viable and cost-effective option for infertile couples with UU infection who are facing infertility issues.
Humans ; Male ; Ureaplasma Infections/complications* ; Female ; Infertility, Male/therapy* ; Ureaplasma urealyticum/isolation & purification* ; Pregnancy ; Adult ; Pregnancy Outcome ; Semen Analysis ; Insemination, Artificial ; Semen/microbiology* ; China

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

OBJECTIVES: To study the clinical characteristics of rashes induced by trimethoprim-sulfamethoxazole (TMP-SMZ) in children treated for pertussis and to inform safe medication practices. METHODS: A retrospective analysis was conducted on 238 children diagnosed with pertussis and treated with TMP-SMZ at Wuhu First People's Hospital from January to August 2024. The incidence and clinical features of rashes were summarized. RESULTS: Of 238 children, 34 (14.3%) developed rashes; 19 (55.9%) were boys, and the 5 to <10-year age group accounted for the highest proportion (70.6%, 24/34). A history of allergic disease was present in 50.0% (17/34). Rashes typically appeared on or after day 7 of therapy (82%, 28/34) and were predominantly erythematous or maculopapular eruptions (97%, 33/34); 71% (24/34) were pruritic. Fever occurred in 56% (19/34); among those who were tested for respiratory viruses, 77% (10/13) were positive for viruses such as rhinovirus and adenovirus. After discontinuation of TMP-SMZ, rashes resolved within 3 days in 97% (33/34) of patients (41% within 1 day; 56% within more than 1 but within 3 days). There was no significant difference in rash incidence between photoprotection and non-photoprotection groups (P>0.05). CONCLUSIONS TMP-SMZ for pertussis can induce rashes, particularly in children aged 5 to <10 years. The eruption is usually a pruritic erythematous or maculopapular rash, with over half of cases accompanied by fever and frequent concomitant viral infections. Most rashes resolve within 3 days after drug withdrawal. The potential association between the rash and sun exposure warrants further investigation.
Humans ; Male ; Child, Preschool ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use* ; Child ; Female ; Exanthema/chemically induced* ; Retrospective Studies ; Infant ; Whooping Cough/drug therapy* ; Adolescent

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms

Objective To investigate the improvement effects of homogeneous fecal microbiota transplantation(FMT)on chemotherapy-induced diarrhea(CID)in mice.Methods Fifteen C57BL/6N mice were divided into control group,CID model group and CID+FMT group according to the random number distribution and remainder grouping method,with 5 mice per group.Control group received no intervention,and their feces were used to prepare fecal bacteria suspension.CID model group was injected intraperitoneally with fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,followed by gavage with 0.1 ml of saline on alternate days.CID+FMT group was given 0.1 ml fecal bacteria suspension gavage on alternate days for one week,followed by intraperitoneal injection of fluorouracil(65 mg/kg)for 5 consecutive days to construct the CID mouse model,with the experiment ending on the 14th day.During the experiment,the mice's food intake and body weight were recorded.At the end of the experiment,the mice were euthanized with deep carbon dioxide anesthesia,and the mice colonic specimens from cecum to anus were collected for hematoxylin and eosin(HE)staining and histopathological examination.Fecal samples were collected for 16S rRNA gene sequencing.Shannon index,Simpson index and Chao1 algorithm were used to analyze the α-diversity species of the intestinal flora in each group of mice.Similarity analysis(Anosim)was used to perform non-parametric on the inter-group differences of intestinal flora among the mice.Linear discriminate analysis size effect(LEfSe)and nonmetric multidimensional scaling(NMDS)were employed to analyze the intestinal dominant flora and the similarity classification relationships in each group of mice.Results The colonic specimen's length from cecum to anus in CID model group was significantly shorter than that in control group(P<0.05),while there was no significant difference between CID+FMT group and CID model group(P>0.05).The weight of mice in CID model group decreased by 42.04%,while control group mice gained 10.24%,with a significant difference between the two groups(P<0.05).The weight of mice in CID+FMT group decreased by 8.12%,which was significantly improved compared to CID model group(P<0.05).HE staining results revealed the intestinal mucosal structure in CID model group was severely damaged,with atrophy and deformation,accompanied by inflammatory cell infiltration,and the pathological score was higher than that of control group(P<0.05).Compared with CID model group,the intestinal mucosal integrity and crypt cells in the CID+FMT group were improved,with less damage,and the pathological score was lower than that of CID model group,but the difference was not statistically significant(P>0.05).The α-diversity analysis showed that there were significant differences in the Shannon,Simpson and Chao1 indices among the three groups(P<0.05).ANOSIM and NMDS analysis revealed that the intestinal flora in CID+FMT group was closer to the normal intestinal flora compared to CID model group.LEfSe analysis showed that the intestinal flora in CID model group was enriched in famliy_Bacteroidaceae,and the intestinal flora in CID+FMT group was similar to that of control group,with an enrichenment of familiy_Enterobacteriaceae.Conclusion Homogeneous FMT can improve the abundance of intestinal flora in CID mice,making it more similar to normal intestinal flora,thereby protecting intestinal mucosa,reducing damage and alleviating the severity of CID.

Objective To investigate the protective effects of secretomes released by three-dimensional cultured mesenchymal stem cells(MSCs)on neurons subjected to seawater immersion(SW)and stretch injury(SI),and to provide new insights into neuronal repair following SW combined with traumatic brain injury(TBI).Methods MSCs were cultured using the hanging drop method,and the conditioned medium(CM)containing MSCs secretomes was collected.A cellular model combining SW with SI was established using mouse hippocampal neuronal cells(HT22 cells).HT22 cells were randomly assigned to five groups:control,SI,SI+SW,SI+CM,and SI+SW+CM groups.Cell viability was assessed using the CCK-8 assay,apoptosis rate was measured by flow cytometry,cell migration ability was evaluated by scratch assay,and the expression levels of apoptosis-related proteins Bcl-2 and Bcl-2-associated protein(Bax),and ferroptosis-related proteins long-chain acyl-CoA synthetase 4(ACSL4)and cyclooxygenase-2(COX-2)were detected by Western blotting.Results Immersion in 15%seawater for 12 h significantly decreased HT22 cell viability(P<0.05).The CCK-8 assay indicated that cell viability in both the SI and SI+SW groups was significantly lower than that in control group after 12 h of treatment(P<0.05).Treatment with CM containing MSCs secretomes significantly increased cell viability in SI+CM group compared to SI group(P<0.0001),and in SI+SW+CM group compared to SI+SW group(P<0.001).Flow cytometry results revealed that the apoptosis rate in SI and SI+SW groups was significantly higher than that in control group(P<0.05 or P<0.001),while in SI+CM group was lower than that in SI group(P<0.05),and in SI+SW+CM group was lower than that in SI+SW group(P<0.05).Western blotting showed that compared to control group,SI and SI+SW groups exhibited reduced Bcl-2 expression level(P<0.01 or P<0.0001)and increased expression levels of Bax,ACSL4,and COX-2(P<0.01 or P<0.0001).Compared to SI group,the SI+CM group displayed increased Bcl-2 expression level(P<0.05)and decreased expression levels of Bax,ACSL4,and COX-2(P<0.05).Compared to SI+SW group,SI+SW+CM group exhibited increased Bcl-2 expression level(P<0.01)and decreased expression levels of Bax,ACSL4,and COX-2(P<0.01 or P<0.001).Scratch assay results demonstrated that at both 12 h and 24 h,the cell migration rate in SI and SI+SW groups was significantly lower than that in control group(P<0.01 or P<0.0001),while the migration rate in SI+CM group was significantly higher than that in SI group(P<0.0001 or P<0.01),and the migration rate in SI+SW+CM group was significantly higher than that in SI+SW group(P<0.0001).Conclusion Secretomes derived from MSCs cultured using the hanging drop method can alleviate neuronal damage caused by SW and TBI,potentially offering a therapeutic approach for SW combined with TBI.

At present, the cause of traditional Chinese medicine(TCM) in China has entered a new period of high-quality development. How to strengthen the foundation for the TCM industry from the source is an important issue that deserves the attention of the authorities, industry, and academia. This study systematically analyzed the regulatory system of TCM raw materials and preparations. The study took the TCM industry chain and the product life cycle as a clue and focused on the dimensions of TCM resource protection and plant cultivation(farming), production and quality supervision of TCM raw materials and preparations, and their market access and distribution. It analyzed the current situation of the regulation of TCM raw materials and preparations under the regulatory system of drugs, discussed the main problems, and put forward corresponding suggestions. The results can provide an important reference value for the subsequent improvement of the regulatory system of drugs and the construction of a prominent regulatory system of drugs in accordance with TCM characteristics.
Drugs, Chinese Herbal/economics* ; Medicine, Chinese Traditional/standards* ; China ; Quality Control ; Humans ; Plants, Medicinal/chemistry*