ObjectiveTo evaluate the therapeutic effects of modified Banxia Xiexintang（MBXT） on polycystic ovary syndrome with insulin resistance（PCOS-IR） rats and reveal its potential mechanisms based on the integrated analysis of transcriptomics and metabolomics. MethodsFemale SD rats were selected， and a PCOS-IR model was established by intragastric administration of letrozole combined with a high-fat diet for 21 days. The modeled rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， and metformin group（0.158 g·kg^-1）， with a normal group set up separately. After 14 days of administration， the estrous cycle was observed， ovarian morphology was examined by hematoxylin-eosin（HE） staining， and the levels of testosterone（T）， estradiol（E₂）， follicle-stimulating hormone（FSH）， and luteinizing hormone（LH） in serum were detected by enzyme-linked immunosorbent assay（ELISA）. Serum metabolites and ovarian tissue gene expression were detected using ultra-performance liquid chromatography-quadrupole-electrostatic orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS） and RNA-Seq technology， respectively， followed by multi-omics integrated analysis. ResultsPharmacodynamic findings revealed that all MBXT dose groups could reversed abnormal estrous cycles in PCOS-IR rats， improve polycystic ovarian lesions， and normalize dysregulated serum hormone levels（T， LH， E₂， FS， P<0.05， P<0.01）. Metabolomic analysis revealed that compared with the model group， MBXT reversed 278 differential metabolites such as estrone and S-formylglutathione， mainly involving pathways such as steroid hormone biosynthesis， glutathione metabolism， and lipid peroxidation regulation. Transcriptomic analysis identified 434 differentially expressed genes， and enrichment analysis revealed that MBXT significantly regulated lipid peroxidation defense systems， including glutathione metabolism， peroxisome function， and fatty acid metabolism， thereby intervening in ferroptosis processes. It also engaged in inflammation-related pathways such as the chemokine signaling pathway. Integrated analysis revealed that both metabolomics and transcriptomics co-enriched metabolic pathways associated with ferroptosis and fatty acid metabolism. And key Hub genes［such as Ras-related C3 botulinum toxin substrate 2 gene（Rac2） and Fas ligand gene（Faslg）］ showed significant correlations with differential metabolites. ConclusionMBXT can effectively ameliorate reproductive dysfunction and metabolic disorders in PCOS-IR rats. Its mechanism may be related to remodeling the immune-metabolism network， particularly by regulating MHC-mediated immune responses， inhibiting local ovarian ferroptosis， and enhancing steroid hormone synthesis pathways.

ObjectiveTo investigate the mechanism of modified Banxia Xiexintang（MBXT） in improving ovarian dysfunction in polycystic ovary syndrome with insulin resistance（PCOS-IR） rats by inhibiting ferroptosis through the adenosine monophosphate（AMP）-activated protein kinase（AMPK）/fatty acid synthase（FASN）/glutathione peroxidase 4（GPX4） signaling pathway. MethodsSeventy-six female SD rats were randomly divided into a normal group（n=13） and a modeling group（n=63）. The modeling group established a PCOS-IR model by intragastric administration of letrozole combined with a high-fat diet for 21 days. After successful modeling， these rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， metformin group（0.158 g·kg^-1）， and high-dose of MBXT combined with ferroptosis inducer Erastin group（15 mg·kg^-1）， with 10 rats in each group. After 14 days of intervention， ovarian pathological morphology was observed by hematoxylin-eosin（HE） staining， the mitochondrial ultrastructure of granulosa cells was observed by transmission electron microscopy（TEM）， ovarian reactive oxygen species（ROS） levels were detected by dihydroethidium（DHE） probe， biochemical methods were used to detect Fe²⁺， malondialdehyde（MDA）， glutathione（GSH） and other indicators in ovarian tissues， serum sex hormone and insulin levels were measured by enzyme-linked immunosorbent assay（ELISA）， and the protein expressions of AMPK， FASN， acyl-CoA synthetase long-chain family member 4（ACSL4）， GPX4， and solute carrier family 7 member 11（SLC7A11） in ovarian tissues were detected by Western blot. ResultsCompared with the normal group， the model group showed polycystic changes in the ovaries， with atrophy of mitochondria in granulosa cells and increased membrane density. Serum levels of testosterone（T）， luteinizing hormone（LH）， and insulin were significantly increased（P<0.01）. The levels of ROS， MDA， 4-hydroxynonenal（4-HNE）， and Fe²⁺ in ovarian tissues were significantly elevated（P<0.01）， while adenosine triphosphate（ATP）， GSH， and reduced nicotinamide adenine dinucleotide phosphate （NADPH） levels were significantly decreased（P<0.01）. The phosphorylation levels of AMPK and acetyl-CoA carboxylase （ACC）， as well as the protein expressions of SLC7A11， GPX4， and ferroptosis suppressor protein 1（FSP1） were significantly downregulated（P<0.01）， whereas the expressions of FASN， ACSL4， and nuclear receptor coactivator 4（NCOA4） were significantly upregulated（P<0.01）. Compared with the model group， MBXT intervention at various doses improved the above pathological changes and biochemical indicators in a dose-dependent manner， with the high-dose group showing the most significant effect（P<0.01）. Compared with the MBXT high-dose group， the high-dose of MBXT combined with ferroptosis inducer Erastin group restored ovarian ferroptosis characteristics in rats， with increased ROS and lipid peroxidation products， and altered expressions of key proteins（P<0.05， P<0.01）. ConclusionMBXT can effectively improve ovarian function and metabolic disorders in PCOS-IR rats. Its mechanism may be related to activating the AMPK/ACC signaling pathway， downregulating FASN and ACSL4 to reduce lipid peroxidation substrates， and restoring glucose-6-phosphate dehydrogenase/phosphoglycerate dehydrogenase（G6PD/PHGDH） metabolic flux to enhance the GPX4/FSP1 antioxidant defense system， thereby inhibiting ferroptosis in ovarian granulosa cells.

Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

OBJECTIVE: To investigate the effectiveness of knee arthroscopy with wire anchor nailing composite double pulley technique in the treatment of anterior cruciate ligament (ACL) tibial avulsion fracture involving the anterior root of the lateral meniscus (LM). METHODS: Clinical data of 35 patients with ACL tibial avulsion fracture involving the anterior root of the LM admitted between January 2019 and September 2023 and met the selection criteria were retrospectively analysed. There were 20 males and 15 females; ages ranged from 10 to 57 years, with a mean of 29 years. The time from injury to surgery ranged from 3 to 20 days, with a mean of 9.6 days. Meyers-McKeever classification included 5 cases of type Ⅱ, 12 cases of type Ⅲ, and 18 cases of type Ⅳ. Preoperative anterior knee instability Lachman test and anterior drawer test were positive. The anterior root of the LM as well as the avulsion fracture block were fixed using suture anchor nails compounded with double pulley technique under arthroscopy. Postoperative X-ray films were performed to assess fracture healing; knee stability was assessed using the anterior drawer test and Lachman test, anterior laxity of the knee was measured by KT-2000, and knee function was assessed using the Lysholm score and the International Knee Documentation Committee (IKDC) score; at last follow-up, the recovery of the meniscus was assessed using the McMurry test and knee hyperextension test. RESULTS: All the patients were successfully operated, the operation time ranged from 56 to 78 minutes,with an average of 67.6 minutes, and there was no nerve or blood vessel injury during operation. Thirty-five cases were followed up 12-18 months with an average of 15.1 months. During the follow-up, there was no infection, knee stiffness, loosening of internal fixation, fracture displacement, or re-fracture. The fractures all healed, with a clinical healing time of 8-15 weeks, averaging 10.9 weeks. At last follow-up, 4 patients had weakly positive anterior drawer test and Lachman test, and the rest were negative; McMurry test and knee hyperextension test were negative; no patient complained of knee extension pain or straightening obstacles, and all the patients resumed their normal life or sports and labour; 16 patients with unclosed epiphyses did not have any epiphyseal injuries or growth disorders. Lysholm score, IKDC score, and KT-2000 anterior knee laxity at last follow-up significantly improved when compared with preoperative ones ( P<0.05). CONCLUSION The treatment of ACL tibial avulsion fracture involving the anterior root of the LM with suture anchor composite double pulley technique can effectively fix the anterior root of the LM while fixing the avulsion fracture block, and better restore the function and stability of the knee joint.
Humans ; Male ; Female ; Adult ; Arthroscopy/methods* ; Adolescent ; Retrospective Studies ; Tibial Fractures/surgery* ; Young Adult ; Middle Aged ; Fractures, Avulsion/surgery* ; Fracture Fixation, Internal/instrumentation* ; Anterior Cruciate Ligament Injuries/surgery* ; Child ; Treatment Outcome ; Suture Anchors ; Menisci, Tibial/surgery* ; Tibial Meniscus Injuries/surgery* ; Bone Nails ; Knee Joint/surgery*

Colorectal cancer is one of the common malignant tumors in digestive system,because of its incidence and mortality rates rising annually in China,seriously threating to people's lives and health.Vitamin D plays an im-portant role in inhibiting colorectal cancer by suppressing tumor cell proliferation,promoting tumor cell apoptosis,inhibiting tumor cell migration,invasion,and angiogenesis and also,enhancing the body's immune system.This article summarizes and analyzes the specific mechanisms by which vitamin D inhibits the occurrence and develop-ment of colorectal cancer,and discusses the current progress in research on vitamin D supplementation,providing new references for the early prevention and adjuvant treatment of colorectal cancer.

Objective : To explore whether chrysophanol(CHR) affects macrophage polarization by promoting mitochondrial biosynthesis through AMPK/PGC-1α pathway. Methods : The molecular docking and binding ability of CHR with AMPK and PGC-1α were predicted by Autodock vina software. Human monocytes(THP-1) were induced to M0 macrophages by phorbol myristate acetate(PMA), and to M1 macrophages by lipopolysaccharide(LPS) combined with interferon-γ(IFN-γ), which were set as Control group. M1 macrophages treated with CHR were set as CHR group. M1 macrophages treated with CHR combined with AMPK inhibitor(Compound C) were set as CHR+Compound C group. The mRNA expression levels of M1 macrophage markers(iNOS, CD86) and mitochondrial biosynthesis related genes(PGC-1α, NFR-1, TFAM) were detected by Quantitative real time polymerase chain reaction(qRT-PCR). The expression level of M1 macrophage marker iNOS was detected by immunofluorescence. The protein expression levels of AMPK, p-AMPK and PGC-1α were detected by Western blot. Results : The docking results showed that the binding energies of CHR with AMPK and PGC-1α were-8.4 kcal/mol and-7.4 kcal/mol, respectively. qRT-PCR results showed that the in vitro model of M1 macrophages was successfully established. Compared with the Control group, CHR treatment significantly increased the mRNA expression of mitochondrial biosynthesis-related genes PGC-1α, NFR-1, and TFAM(P<0.001). Compared with CHR treatment group, CHR combined with Compound C treatment significantly decreased the mRNA expression levels of mitochondrial biosynthesis-related genes PGC-1α, NFR-1, and TFAM(P<0.05). Immunofluorescence results showed that CHR treatment inhibited the protein expression of iNOS compared with the Control group(P<0.001). Compared with CHR treatment group,CHR combined with Compound C treatment reversed the inhibitory effect of CHR on i NOS protein expression(P<0.05). Western blot results showed that compared with the Control group,the CHR treatment group had significant increase in the protein expression levels of p-AMPK and PGC-1α(P<0.001).Compared with CHR treatment group,CHR combined with Compound C treatment significantly decreased the protein expression levels of p-AMPK and PGC-1α(P<0.05). Conclusion Chrysophanol may inhibit macrophage polarization to M1 by activating AMPK/PGC-1α signaling pathway to promote mitochondrial biosynthesis.

Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P＜0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P＜0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P＜0.05)and the daytime restraint group(P＜0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P＜0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P＜0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P＜0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P＜0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P＜0.01,P＜0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P＜0.05,P＜0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

[Objective]To summarize Professor LI Xinmin's clinical experience in treating functional constipation in children based on the theory of spleen movement.[Methods]Through learning from the teacher,reading ancient medical books and sorting out clinical medical cases,this paper expounds the theoretical origin of the spleen-transportation theory,analyzes Professor LI's exploration of the etiology and pathogenesis of functional constipation in children from the perspective of"spleen transportation",as well as the clinical experience in treating children's functional constipation with the spleen-transportation theory,and attaches a verified case for evidence.[Results]Professor LI holds that the main etiology of functional constipation in children is the damage to the spleen and stomach caused by dietary stagnation.The key pathogenesis is characterized by"dry fecal accumulation being the secondary aspect with dysfunction of large intestine conduction,and spleen-stomach deficiency being the primary aspect with disharmony of Qi movement in internal organs",among which the disorder of ascending-descending mechanisms in the spleen-stomach and liver-lung axis is particularly prominent.Guided by the"spleen-transportation"theory and the principle of"three-adaptation therapy",clinical treatment employs the strategies of"strengthening the spleen for root cultivation with tonification in transportation,regulating pivotal mechanisms through combined therapies",forming the spleen-transporting pivot-regulation method featured by"dredging-transportation and pivot-regulation".The self-formulated Yunpi Decoction is used to invigorate spleen-earth,focusing on ascending spleen-Yang,regulating middle-Jiao,and regulating Qi movement.In clinical practice,therapies like digestion-promoting,heat-clearing,purging and Qi-supplementing are flexibly integrated based on concomitant syndromes.The harmony method is adeptly applied to reconcile cold-heat and deficiency-excess,emphasizing that medications should be mild to avoid excessive purgation from damaging vital Qi.The pathogenesis of the attached case belonged to spleen deficiency and lack of health,with poor pivot function and internal food stagnation.The treatment adopted the methods of invigorating the spleen and stomach,regulating Qi and promoting smoothness,guiding stagnation and relieving constipation,and administered with the self-designed modified Yunpi Decoction.[Conclusion]Based on the"spleen-transportation theory",Professor LI applies the spleen-transportation and pivot-regulation method featuring dredging-transportation and pivot-regulation.With its unique theory,this approach provides new ideas and methods for clinical practice,making it worthy of promotion and learning.

Radiation‐induced lung injury (RILI) is one of the common and serious complications in chest cancer patients after undergoing radiotherapy. In recent years, gut microbiota has garnered attention as a research hotspot. Multiple studies found that it has preventive and therapeutic effects on RILI. It can exert its effects through various mechanisms including the regulation of the immune system, the gut‐lung axis and its own metabolites, etc. In this article, the mechanism of RILI was elucidated and the protective mechanism of gut microbiota against RILI was comprehensively analyzed, providing new insights for the prevention and treatment of RILI in clinical practice and offering new methods to improve patient prognosis and enhance the quality of life.