ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanisms by which Mahuang Lianqiao Chixiaodoutang （MLC） improves obesity-type polycystic ovary syndrome （PCOS） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsThirty-six female Sprague-Dawley （SD） rats were randomly divided into a blank control group （Con） and an obesity-type PCOS model preparation group. The model was induced by gavage with letrozole （1 mg·kg^-1） combined with a high-fat diet （HFD）. After model establishment， the obesity-type PCOS model preparation group was further divided into the model group （Mod， normal saline）， metformin group （Met， 0.3 g·kg^-1）， low-dose MLC group （MLC-L， 4.3 g·kg^-1）， medium-dose MLC group （MLC-M， 8.6 g·kg^-1）， and high-dose MLC group （MLC-H， 17.2 g·kg^-1）. Active components of MLC and targets of obesity-type PCOS were screened from databases， a protein-protein interaction （PPI） network was constructed， and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed. The gut microbiota structure was analyzed based on 16S rRNA sequencing and correlated with network pharmacology pathways. Body weight and estrous cycle were dynamically monitored. Ovarian morphology was observed by hematoxylin-eosin （HE） staining. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was used to detect levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， anti-Müllerian hormone （AMH）， testosterone （T）， and estradiol （E₂）. Western blot was used to detect the protein expression levels of phosphorylated PI3K/PI3K （p-PI3K/PI3K）， phosphorylated Akt/Akt （p-Akt/Akt）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. ResultsNetwork pharmacology screening identified 124 active components of MLC and 408 overlapping targets between the herbal formula and the disease. Core targets such as Akt1 and Bcl-2 were revealed. As indicated by 16S rRNA sequencing， the abundances of Lachnospiraceae， Lachnoclostridium， and Dorea were increased in the MLC groups （P<0.05）， while the abundance of Veillonella was decreased （P<0.05）. KEGG correlation analysis integrating network pharmacology and gut microbiota data showed significant enrichment of the PI3K/Akt signaling pathway. Animal experiments showed that， compared with the Mod group， body weight decreased to normal levels in the Met， MLC-M， and MLC-H groups. The estrous cycle became regular. The number of corpora lutea increased and cystic follicles decreased. Serum levels of T， FSH， and LH/FSH were reduced （P<0.05， P<0.01）， while the E₂ level was increased （P<0.01）. Ovarian cell apoptosis was reduced （P<0.01）， and the protein expression levels of p-PI3K/PI3K， p-Akt/Akt， and Bcl-2 in ovarian tissue were significantly increased， whereas Bax protein expression was significantly decreased （P<0.05， P<0.01）. ConclusionMLC can regulate gut microbiota structure， effectively improve ovarian pathology in rats with obesity-type PCOS， and inhibit ovarian granulosa cell apoptosis. The mechanism may be associated with upregulation of the PI3K/Akt signaling pathway.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To explore the effect of Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) with chemotherapy on breast cancer patients who got agranulocytosis of 3 to 4 degree, agranulocytosis with fever (FN) and the influential factors of relative dose intensity (RDI) chemotherapy scheme. Meantime, the value of CD34 + and CD45 in peripheral blood on predicting agranulocytosis of 3-4 degree were investigated.Methods:A total of 104 women with breast cancer were treated at Huzhou Maternal and Child Health Hospital and Cancer Hospital of Zhejiang Province from Jan. 2022 to Sep. 2023. All subjects received primary prevention with PEG-rhG-CSF during chemotherapy. The clinical risk factors of agranulocytosis, FN and RDI were analyzed. The levels of CD34 + and CD45 in peripheral blood samples were analyzed by flow cytometry. Then the predictive value of the receiver characteristic curve (ROC) for Grade 3 to 4 agranulocytosis after primary prophylaxis with PEG-rhG-CSF for breast cancer chemotherapy was evaluated.Results:Among 104 breast cancer patients who received primary prevention of PEG-rhG-CSF during chemotherapy, 28 patients had agranulocytosis of 3 to 4 grade, 10 patients got FN, and 12 patients developed RDI<85%. The results of single factor analysis showed that CD34 +, CD45 and chemotherapy scheme were the influential factors of agranulocytosis of 3 to 4 degree, and low RDI of chemotherapy scheme ( OR=0.584, OR=0.999, OR=2.299, OR=0.100, OR=0.999, OR=3.088, P<0.05) . It also showed that CD34 + and chemotherapy scheme were the influential factors of FN ( OR=0.099, OR=2.667, P<0.05) . Multivariate Logistic regression analysis showed that CD34 +, CD45 and intensive chemotherapy were the independent risk factors of agranulocytosis of 3 to 4 degree after primary prevention with PEG-rhG-CSF ( OR=0.602, OR=0.999, OR=20.174, P<0.05) . CD34 + and intensive chemotherapy scheme were the independent influential factors of FN and RDI of chemotherapy scheme after primary prevention with PEG-RHG-CSF ( OR=0.072, OR=33.934, OR=0.086, OR=54.788, P<0.05) . The area under the curve (AUC) of CD34 + were 0.767 (95% CI:0.659-0.876) , AUC of CD45 were 0.743 (95% CI:0.644-0.842) , and the AUC of combined two indexes was 0.825 (95% CI:0.730-0.920) , which was higher than that of single index. So AUC of CD34 + and CD45 can be used for predicting agranulocytosis of grade 3 to 4 in breast cancer patients receiving primary prophylaxis with PEG-rhG-CSF. Conclusions:The levels of CD34 + and CD45 in peripheral blood of breast cancer patients with agranulocytosis of grade 3 to 4 receiving primary prevention with PEG-rhG-CSF during chemotherapy are lower. Combined detection of CD34 + and CD45 in peripheral blood can predict the occurrence of agranulocytosis of grade 3 to 4 in breast cancer patients after primary prevention with PEG-rhG-CSF. Also it can provide a reliable basis for assessing the risk of grade 3 to 4 agranulocytosis.

Objective:To compare the accuracy of a Chinese large language model (LLM) and radiologists in Chinese middle level professional qualification examination of radiology, and evaluate the quality of answer reasoning provided by the Chinese LLM.Methods:In this study, 100 high-quality questions were selected using stratified random sampling to form a test set. We asked the ERNIE Bot by dialogues on the website to provide the correct answers and answer reasoning for these questions. These questions were also answered by 15 radiologists with different levels of experience. The accuracy of Chinese LLM and that of radiologists were compared. Two radiologists evaluated the quality of answer reasoning using a 5-point semi-quantitative scale.Results:The accuracy of ERNIE Bot was 60.00%, which was lower than the median (interquartile) accuracy of 67.00% (64.00%, 73.00%) for radiologists, and the difference was statistically significant ( W=2.47, P=0.013). The word count of the reasoning provided by Ernie Bot was (196.44±99.25) words, with no significant difference in word count between correct and incorrect answer reasoning, which were (211.03±107.53) words and (174.55±81.84) words, respectively ( t=1.82, P=0.072). Among the correct answers, the quality of reasoning was scored as follows: 1 point for 3 questions, 2 points for 9 questions, 3 points for 12 questions, and 4 points for 36 questions. No reasoning received a score of 5. Conclusions:Chinese LLM demonstrates a certain level of medical knowledge and clinical reasoning ability, which can assist clinical teachers in educational activities. However, it is not yet able to independently tutor residents and lacks the ability of invitational and heuristic teaching.

Objective:To investigate the current status of Chinese-foreign cooperative education programs for medical majors, and to discuss the potential problems and development trends of this field.Methods:Related data were collected from the information platform of Chinese-Foreign Cooperation in Running Schools by Ministry of Education of the People's Republic of China, and the characteristics of Chinese-foreign cooperative education programs for medical majors were extracted for analysis. Categorical data were expressed as frequency (percentage), and continuous data were expressed as mean±standard deviation.Results:A total of 83 Chinese-foreign cooperative education programs for medical majors were included in the study, accounting for only 3.45% (83/2 406) of all programs. Chinese partners in these cooperative programs were mainly from East China (41 programs, 49.40%), while foreign partners were mainly from Europe (39 programs, 46.99%). The mean duration of these programs was (3.61±0.88) years, with an enrollment of (87.08±35.52) students. Most of the students were included in National General Higher Education Enrollment Plan (79 programs, 95.18%), and the main majors included nursing (39 programs, 46.99%), medical technology (19 programs, 22.89%), and clinical medicine (11 programs, 13.25%), with the main enrollment level of junior college (45 programs, 54.22%). Chinese partners in the cooperative programs mainly issued academic certificate (45 programs, 54.22%) or academic certificate plus degree certificate (36 programs, 43.37%), while most foreign partners did not issue such certificates (44 programs, 53.01%).Conclusions:There are several problems in Chinese-foreign cooperative education programs for medical majors, such as a limited number of programs, a significant regional difference, an imbalanced distribution of specialties, a low level of education, and inconsistency in issuance of certificates, which still requires further improvement and standardization. However, there are also high-level and high-quality programs for reference.

Objective Exploring the effect of Bian-stone-based herbal heat therapy on herbal heat ironing in gastrointestinal reactions during the preconditioning period of hematopoietic stem cell transplantation patients.Methods Convenience sampling method was used to select 68 cases of hematopoietic stem cell transplantation patients who attended the hematology department of a tertiary-level Chinese medicine hospital in Hangzhou from October 2023 to April 2024 as the study subjects,and the SPSS 26.0 statistical software was used to generate a random number for grouping into an experimental and a control group,with 34 cases in each group.On the basis of intravenous antiemetic medication and routine,the experimental group implemented the Bian-stone-based herbal heat therapy on the basis of intravenous antiemetic medication and conventional nursing care.In the control group,intravenous antiemetic drugs and routine care were used,and the intervention duration of both groups was 14 d,of which 7 d was a course of treatment,with a total of 2 courses of treatment.The incidence of gastroin-testinal reactions,Gastrointestinal Symptom Rating Scale(GSRS)score,Pepsin Ⅰ(PG Ⅰ),Pepsin Ⅱ(PG Ⅱ),and the ratio of PG Ⅰ to PG Ⅱ(PGR)before and after the intervention were compared between the 2 groups.Results The final sample of 66 cases was collected in this study,and 1 patient was dislodged from each of the control group and the experimental group.The comparison of the incidence of gastrointestinal reactions between the 2 groups within 14 days showed that the incidences of nausea,vomiting,abdominal distension,and diarrhea were lower in the experimental group than those in the control group(P＜0.05).GSRS scores on days 1,8,and 14 of intervention were compared,and there were effects between groups in both groups(F=5.338,P=0.017).The levels of PG Ⅰ,PG Ⅱ in the experimental group on day 8 of the intervention were lower than those in the control group.The levels of PGR was higher than that in the control group(all P＜0.05).The safety of the 2 groups after treatment was evaluated,and the results showed that no serious adverse events occurred in the 2 groups.Conclusion Bian-stone-based herbal heat therapy can improve gastrointestinal reactions and reduce the incidence of gastrointestinal reactions during the preconditioning period of hematopoietic stem cell transplantation patients,which provides clinical guidance for the application of Bian-stone-based herbal heat therapy by nursing staff in the future.

In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

With the increasing demand for dynamic,real-time and rapid qualitative analysis of chemical composition in areas such as emergency response and space exploration,chip-scale mass spectrometers have attracted significant attention.These devices are expected to drive the integration of mass spectrometry with micro/nano-fabrication and intelligent sensing technologies,fostering profound innovation and breakthroughs in analytical chemistry.As an excellent mass analyzer,the ion trap exhibits numerous advantages,and its miniaturization creates favorable conditions for the high-density integration of miniature mass spectrometers.However,the reduction in ion storage capacity may compromise its sensitivity and dynamic range,rendering the study of ion unidirectional ejection in highly miniaturized ion traps of significant practical importance.In this work,a research was conducted on achieving efficient ion unidirectional ejection while maintaining high mass resolution in the extremely miniature hyperbolic linear ion trap(M-HLIT)with a field radius of 1 mm,and an electric field compensation method was proposed,which combined asymmetric electrode stretching and unbalanced RF voltage to achieve high-precision optimization of the electric field composition.Simulations showed that in an ideal structure,this method achieved 100％unidirectional ejection efficiency with the mass resolution of 518,significantly outperforming traditional asymmetric structure method(365)and unbalanced voltage method(321).Following the introduction of ion ejection slots,further optimization through bidirectional stretching and electrical parameters improved the resolution to 790 while maintaining a unidirectional ejection efficiency of 93％.This method eliminated the requirement for additional excitation voltage,offering an ideal solution for the miniature mass analyzer with high detection performance of chip-level mass spectrometers.

Hematologic malignancies,such as lymphoma,myeloma,and myeloid neoplasms,can occur in extramedullary tissues.Traditional histopathological morphology and immunohistochemical staining have lim-itations,including time-consuming specimen processing,prolonged reporting cycles,and relatively low sensi-tivity in cases of limited cell numbers.Flow cytometry offers significant advantages in detecting tissue sam-ples,such as rapid processing,shorter reporting cycles,and high accuracy and sensitivity,making it an effective complement to histopathological and immunohistochemical methods.However,the application of flow cytome-try in tissue sample detection currently lacks standardized protocols for sample collection and preservation,single-cell suspension preparation,antibody panel design for limited samples,data analysis,and result repor-ting.To promote the standardized application of flow cytometry in detecting hematologic tumor cells in tissue samples,the Cell Analysis Professional Committee of the Chinese Society of Biotechnology organized experts to develop the Chinese Expert Consensus on Flow Cytometry for Detecting Hematologic Tumor Cells in Tis-sue Samples(hereinafter referred to as the Consensus).This Consensus elaborates on the technical aspects of flow cytometry for tissue sample detection,covering sample processing,antibody panel design,data analysis,reporting content,and quality management.It particularly emphasizes recommended antibody panels and data analysis methods for flow cytometry when tissue sample cell counts are low.This article aims to interpret the key points of the Consensus to facilitate its better application in clinical practice.