ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss （RPL） by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus （Shoutai Wan， Juyuan Jian）-of traditional Chinese medicine （TCM） at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c （blank group） and DBA/2 （modeling group） mice separately. Pregnant mice in the modeling group were randomly grouped as follows： high/low-dose Shoutai Wan， high/low-dose Juyuan Jian， model （RPL）， and positive control （dydrogesterone）， with 10 mice in each group. Starting from the day after the detection of the vaginal plug， mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention， the following indicators were measured. ① Macroscopic evaluation： general conditions， uterine wet weight， embryo loss rate， four coagulation parameters ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， fibrinogen （FIB）， and thrombin time （TT）］， and peripheral blood estradiol （E₂） and progesterone （Pg） levels. The decidua with embryos was stained with hematoxylin-eosin （HE） and evaluated by transmission electron microscopy （TEM）. The expression of B-cell lymphoma-2 （Bcl-2）， vascular endothelial growth factor （VEGF）， angiotensin Ⅱ （AngⅡ）， matrix metalloproteinase-2 （MMP-2）， interleukin-6 （IL-6）， leukemia inhibitory factor （LIF）， CXC chemokine ligand 12 （CXCL12）， and microtubule-associated protein 1 light chain 3 homolog （LC3）Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level： The decidua with embryos from the blank， model， high-dose Shoutai Wan， and high-dose Juyuan Jian groups （6 mice per group， with 3 single-cell samples per group， totaling 24 mice） were analyzed by the BD Rhapsody™ platform， and the whole-cell atlas was drawn by uniform manifold approximation and projection （UMAP） dimensionality reduction clustering combined with the single-cell mouse cell atlas （scMCA）. The differentially expressed genes （DEGs） and cell interaction networks were analyzed via Gene Ontology （GO）， Kyoto Encyclopedia of Genes and Genomes （KEGG）， and CellChat， and the protein-protein interaction （PPI） map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells （natural killer cells， NK cells） from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group， the RPL group showed an increase in the embryo loss rate （P<0.01）， down-regulated expression of Bcl-2， LIF， MMP-2， and Vegf in the decidua with embryos （P<0.05）， up-regulated protein levels of CXCL-12， AngⅡ， and IL-6 （P<0.05）， blocked angiogenesis， apoptosis-inflammation imbalance， and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance， and Shoutai pill showed superior performance in restoring the E₂ level to the Pg level （P<0.05）. ② Single-cell transcriptome analysis indicated that compared with the blank group， the RPL group showed differences in multiple key cell populations such as decidual cells， trophoblast cells， endothelial cells， erythroblasts， NK cells， and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group， high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer （upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes） and macrophages （upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes） through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins， cell adhesion， and programmed cell death， thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells （up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes） and macrophages （up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes）， which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D， CDH5， GDF， and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 （STAT3） and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis （TWEAK） signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7， a decreased proportion of reparative dNK4， and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1， thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method （Shoutai Wan） has an advantage in regulating the phenotypes of unfolded protein， cell adhesion， and programmed cell death， and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method （Juyuan Jian） has an advantage in regulating epithelial-mesenchymal transition （EMT）， angiogenesis， and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.

Objective To explore the number of peripheral blood regulatory T cells (Treg) in patients with chronic kidney disease (CKD) and its correlation with vascular calcification. Methods This was a single-center, cross-sectional, and observational study. Non-dialysis patients with CKD treated at Zhongshan Hospital, Fudan University from March 2021 to March 2022 were enrolled. Abdominal aortic calcification (AAC) was assessed using lateral abdominal X-ray. Number of Treg and cytokine levels were measured by flow cytometry. Logistic regression analysis was performed to evaluate the related factors for AAC in CKD patients. Results A total of 83 patients were included, aged 17–86 years, with 57 males (68.7%). The distribution of CKD stages was as follows: stage G1 in 7 patients (8.4%), stage G2 in 17 patients (20.5%), stage G3 in 21 patients (25.3%), stage G4 in 19 patients (22.9%), and stage G5 in 19 patients (22.9%). No AAC was observed in patients with stages G1 and G2, while the prevalence of AAC in patients with stages G3, G4, and G5 was 23.8%, 21.1%, and 26.3%, respectively. Compared with stage G1 patients, those with stages G3–5 showed decreased number of peripheral blood Treg and elevated levels of interleukin (IL)-6 and IL-17F (P＜0.05). The area under the receiver operating characteristic curve for number of peripheral blood Treg in predicting AAC in CKD patients was 0.766 (95%CI 0.652–0.879, P＝0.002). Logistic regression analysis showed that decreased number of Treg was related factor for AAC in CKD patients (OR＝0.957, 95%CI 0.922–0.992, P＝0.018). Conclusion As CKD progresses, number of peripheral blood Treg significantly decreases, which is correlated with AAC in CKD patients.

Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

Metabolomics covers a wide range of applications in life sciences, biomedicine, and phytology. Data acquisition (to achieve high coverage and efficiency) and analysis (to pursue good classification) are two key segments involved in metabolomics workflows. Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups. However, insufficient feature extraction, inappropriate feature selection, overfitting, or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused. Using two ginseng varieties, namely Panax japonicus (PJ) and Panax japonicus var. major (PJvm), containing the similar ginsenosides, we integrated pseudo-targeted metabolomics and deep neural network (DNN) modeling to achieve accurate species differentiation. A pseudo-targeted metabolomics approach was optimized through data acquisition mode, ion pairs generation, comparison between multiple reaction monitoring (MRM) and scheduled MRM (sMRM), and chromatographic elution gradient. In total, 1980 ion pairs were monitored within 23 min, allowing for the most comprehensive ginseng metabolome analysis. The established DNN model demonstrated excellent classification performance (in terms of accuracy, precision, recall, F1 score, area under the curve, and receiver operating characteristic (ROC)) using the entire metabolome data and feature-selection dataset, exhibiting superior advantages over random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and multilayer perceptron (MLP). Moreover, DNNs were advantageous for automated feature learning, nonlinear modeling, adaptability, and generalization. This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples. This established approach holds promise for plant metabolomics and is not limited to ginseng.

Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

Objective:To analyze change trend of disease burden of chronic kidney disease (CKD) mortality between 2012 and 2023 in Chongqing, and provide suggestion for CKD prevention.Methods:The mortality data of CKD were collected from Chongqing death registration between 2012 and 2023 according to International Classification of Diseases 10 th. The data were analyzed to calculate mortality rate, standardized mortality rate, age specific mortality rate, and the rate of years of life lost (YLL) and proportion by using software SPSS 26.0. The mortality rate of CKD between men and women, urban area and rural area were compared by χ2 test. The change trend was described by average annual percent of change (AAPC). Results:The mortality rate and standardized mortality rate of CKD were 7.94/100 000 and 4.63/100 000 respectively in 2012 and 6.70/100 000 and 2.79/100 000 respectively in 2023 in Chongqing. The difference in change of CKD mortality rate was not significant (AAPC=-0.79%, t=-1.60, P=0.273). However, the standardized mortality rate of CKD decreased by 3.59% ( t=-3.98, P=0.003) from 2012 to 2023. The mortality rate of CKD was higher in men than in women in 2014 and 2022, the differences were significant (all P<0.05). The standardized mortality rate of CKD in men and women decreased by 3.17% and 4.11% respectively between 2012 and 2023, the difference was significant (all P<0.05). The mortality rate of CKD had been higher in urban area than in rural area since 2016 (all P<0.05). During this period, the mortality rate and standardized mortality rate of CKD in urban area remained stable, but the mortality rate and standardized mortality rate of CKD in rural area showed average annual decreases of 2.21% and 4.90%, the differences were significant (all P<0.05). The proportion of CKD due to hypertension decreased, but the proportion of CKD due to diabetes and other causes increased. The rate of age standardized YLL of CKD showed an average annual decrease of 2.83%, the differences were significant ( P=0.011). Conclusions:The standardized mortality rate and age standardized YLL of CKD decreased from 2012 to 2023 in Chongqing. Men, urban residents and the elderly are key populations in CKD prevention.

[Summary]Diabetic peripheral neuropathy(DPN)is one of the most common complications of diabetes.The blood nerve barrier(BNB)is a barrier structure located in peripheral nerve tissue,protecting nerve tissue from toxic substances in the blood and maintaining material exchange and information transmission between nerves and blood.Studies have shown that changes in BNB may be the initial event leading to the occurrence of DPN.After BNB is destroyed,blood-borne pathogens can directly damage peripheral nerves and cause DPN.This article will review the physiological and pathological characteristics of BNB,the relationship between BNB and DPN,and the research progress in targeting BNB for the treatment of DPN.

Objective To analyze the trends of suicide mortality and disease burden among the elderly aged 60 and above in Chongqing from 2012 to 2023,providing evidence for targeted interventions.Methods Death cases of elderly aged 60 and above were extracted from death registration between 2012 and 2023 according to death records(International Statistical Classification of Diseases and Related Health Problems,10th version:X60-X84,Y87).The data were analyzed to calculate indicators such as the mortality rate,standardized mortality rate,years of life lost(YLL)rate,and average years of life lost(AYLL),and the composition ratio of different causes of death with using Excel 2010 and SPSS 26.0.The comparison of mortality rates between male and female,urban and rural area was conducted using the x2 test.The trend changes of the rates were expressed by the annual percentage change(APC)and the average annual percentage change(AAPC).Results From 2012 to 2023,the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above generally showed a downward trend,decreasing by 3.54%and 4.02%,respectively(P<0.05).From 2012 to 2016,the suicide mortality rate increased by an average of 4.53%per year,and from 2016 to 2021,it decreased by an average of 8.91%per year,and both trends were significant(P<0.05).Only in 2020 and 2022,the male suicide mortality rate was significantly higher than that of females(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate of males and females decreased by an average of 2.86%,3.44%,4.21%,and 4.69%per year respectively,and the trends were significant(P<0.05).The suicide mortality rate of the elderly aged 60 and above in rural areas was significantly higher than that in urban areas over the years(P<0.05).From 2012 to 2023,the suicide mortality rate and standardized mortality rate in urban areas remained relatively stable(P>0.05),while the suicide mortality rate and standardized mortality rate of the elderly aged 60 and above in rural areas decreased by an average of 3.44%and 4.02%per year respectively,and the trends were significant(P<0.05).The YLL rate and AYLL caused by suicide among the elderly aged 60 and above decreased from 3.03‰ and 18.54 years in 2012 to 2.26‰ and 17.50 years in 2023 respectively,and the AAPC were-4.02%and-0.60%respectively,and the trends were significant(P<0.05).By comparing the composition of deaths by different suicide methods over the years,it was found that the proportion of deaths due to pesticide poisoning showed a downward trend,while the proportions of deaths by hanging,jumping from a height,and drowning showed an upward trend.Conclusion The suicide mortality rate of the elderly aged 60 and above in Chongqing is relatively high.Although demonstrating an overall downward trend,enhanced efforts toward early identification and intervention for elderly suicide should be enhanced.

Objective To compare the performance of two different deep learning models,VTcGAN and Pix2pix,in generating synthetic computed tomography(sCT)from magnetic resonance imaging(MRI)of nasopharyngeal carcinoma(NPC),and to evaluate their accuracies in treatment planning dose calculations.Methods MRI and CT images as well as treatment planning data of 115 NPC patients were retrospectively selected,and paired dataset was obtained through rigid image registration,with 105 cases as the training set,and the remaining 10 cases as the test set.Two kinds of models,namely Pix2pix model based on conventional convolutional neural network and the improved VTcGAN model based on Transformer network,were constructed with the consistent structure except for the bottleneck network in the generator.The generated sCT images(sCTPix2pix and sCTVTcGAN)were assessed in terms of image quality,intensity value and dosimetric differences.Results For the cases in test set,the mean error,mean absolute error,peak signal-to-noise ratio,and structural similarity index between the ground truth CT images and the sCTPix2pix were(-0.86±12.42)HU,(40.77±3.06)HU,(33.45±0.62)dB,and 0.928±0.013,respectively;and those between the ground truth CT images and the sCTVTcGAN were(-1.10±8.56)HU,(37.40±2.08)HU,(34.33±0.45)dB,and 0.936±0.009,respectively.For the criterion of 1 mm/1%,the averaged gamma passing rates of sCTPix2pix and sCTVTcGAN were(96.62±1.08)%and(96.88±0.99)%at a dose threshold of 10%,(94.31±1.03)%and(94.72±0.91)%at a dose threshold of 50%,(84.62±1.74)%and(86.06±1.41)%at a dose threshold of 80%,respectively.Conclusion The proposed VTcGAN model is superior to the traditional Pix2pix model in terms of accuracy in generating sCT from MRI of NPC,and it can fulfill the requirements for dose calculation in the MRI-Only workflow.