ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg^-1， respectively. The metformin hydrochloride group received 0.135 g·kg^-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.

Low anterior resection syndrome （LARS） is a common complication of sphincter-preserving rectal cancer surgery， and its manifestations change dynamically at different stages. By analyzing and summarizing the clinical symptoms and pathomechanism evolution of LARS across different stages， this paper proposes a staged prevention and treatment strategy using acupuncture. During perioperative stage， the main principle is activating the transport function of the body， supplemented by regulating the mind， with the use of dredging the bowels as needed. During the stoma reversal stage， treatment focuses primarily on fortifying the spleen， with draining dampness as a supplementary method， to help consolidate the intestines. During the radiotherapy or chemotherapy stage， the main focus is reinfor-cing healthy qi， with reducing toxin as an adjunct， to achieve the effect of activating the transport of the pivot. During the survival management stage， treatment primarily focuses on tonifying the kidneys and secondarily on fortifying the spleen， with regulating the corporeal soul as the therapeutic emphasis. Acupoints are selected and combined in accordance with the treatment principles at each stage， and different stimulation methods such as electroacupuncture and moxibustion are applied. An analysis of the mechanisms underlying acupuncture for LARS is also provided， offering a theoretical basis and practical approach for the prevention and treatment of LARS with acupuncture.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Metabolic diseases characterized by an imbalance in energy homeostasis represent a significant global health challenge. Individuals with metabolic diseases often suffer from complications related to disorders in lipid metabolism, such as obesity and non-alcoholic fatty liver disease (NAFLD). Understanding core genes involved in lipid metabolism can advance strategies for the prevention and treatment of these conditions. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in lipid metabolism that converts saturated fatty acids into monounsaturated fatty acids. SCD1 plays a crucial regulatory role in numerous physiological and pathological processes, including energy homeostasis, glycolipid metabolism, autophagy, and inflammation. Abnormal transcription and epigenetic activation of Scd1 contribute to abnormal lipid accumulation by regulating multiple signaling axes, thereby promoting the development of obesity, NAFLD, diabetes, and cancer. This review comprehensively summarizes the key role of SCD1 as a metabolic hub gene in various (patho)physiological contexts. Further it explores potential translational avenues, focusing on the development of novel SCD1 inhibitors across interdisciplinary fields, aiming to provide new insights and approaches for targeting SCD1 in the prevention and treatment of metabolic diseases.
Stearoyl-CoA Desaturase/metabolism* ; Humans ; Metabolic Diseases/physiopathology* ; Lipid Metabolism/physiology* ; Animals ; Obesity/enzymology* ; Non-alcoholic Fatty Liver Disease

In this paper, near-infrared spectroscopy(NIRS) was employed to analyze 129 batches of commercial products of Reduning Injection. The batch reporting rate was estimated according to the report of Reduning Injection in the direct adverse drug reaction(ADR) reporting system of the drug marketing authorization holder of the Center for Drug Reevaluation of the National Medical Products Administration(National Center for ADR Monitoring) from August 2021 to August 2022. According to the batch reporting rate, the samples of Reduning Injection were classified into those with potential risks and those being safe. No processing, random oversampling(ROS), random undersampling(RUS), and synthetic minority over-sampling technique(SMOTE) were then employed to balance the unbalanced data. After the samples were classified according to appropriate sampling methods, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA), uninformative variables elimination(UVE), and genetic algorithm(GA) were respectively adopted to screen the features of spectral data. Then, support vector machine(SVM), logistic regression(LR), k-nearest neighbors(KNN), naive bayes(NB), random forest(RF), and artificial neural network(ANN) were adopted to establish the risk prediction models. The effects of the four feature extraction methods on the accuracy of the models were compared. The optimal method was selected, and bayesian optimization was performned to optimize the model parameters to improve the accuracy and robustness of model prediction. To explore the correlations between potential risks of clinical use and quality test data, TreeNet was employed to identify potential quality parameters affecting the clinical safety of Reduning Injection. The results showed that the models established with the SVM, LR, KNN, NB, RF, and ANN algorithms had the F1 scores of 0.85, 0.85, 0.86, 0.80, 0.88, and 0.85 and the accuracy of 88%, 88%, 88%, 85%, 91%, and 88%, respectively, and the prediction time was less than 5 s. The results indicated that the established models were accurate and efficient. Therefore, near infrared spectroscopy combined with machine learning algorithms can quickly predict the potential risks of clinical use of Reduning Injection in batches. Three key quality parameters that may affect clinical safety were identified by TreeNet, which provided a scientific basis for improving the safety standards of Reduning Injection.
Spectroscopy, Near-Infrared/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Machine Learning ; Algorithms ; Humans ; Quality Control

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics