Sarcopenia is a systemic skeletal muscle disease characterized by the gradual decline of muscle mass，strength，and function，and its occurrence and development are related to multiple factors，involving several signaling pathways. Among them，the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway，as a key pathway regulating cellular growth，survival，and metabolism，plays an important role in the formation and development of sarcopenia. Its abnormal activation or deactivation may lead to an imbalance in muscle protein metabolism，resulting in muscle atrophy and reduction. Modern medicine is still in the exploratory stage of treatment for sarcopenia. Traditional Chinese medicine （TCM），with its multi-pathway and multi-target characteristics，has shown increasing advantages in the prevention and treatment of sarcopenia. In recent years，various monomers， extracts，and compound formulas of TCM have been proven to effectively prevent and treat sarcopenia by promoting muscle cell protein synthesis，reducing protein degradation，inhibiting cell apoptosis and inflammatory response，and improving mitochondrial function. This paper reviewed the improvement effects of TCM on sarcopenia based on the PI3K/Akt pathway and explored its specific action mechanisms， aiming to provide new insights for the treatment of sarcopenia with TCM.

Chronic post-surgical pain (CPSP) is a common long-term complication following lung surgery. Its high incidence significantly impacts patients’ quality of life and functional recovery, and imposes a substantial socioeconomic burden. This consensus aims to systematically establish a standardized integrated Chinese and Western medicine diagnostic and treatment framework for chronic post-lung surgery pain (CPLSP). Based on the latest domestic and international evidence-based medical research and multidisciplinary clinical experience, the working group comprehensively elaborates on core issues regarding CPLSP, including its definition, epidemiology, pathogenesis, clinical assessment, Western medical treatment, traditional Chinese medicine (TCM) treatment, and integrated strategies. The consensus emphasizes a patient-centered approach, adhering to the principles of multimodality, individualization, and stepwise management, highlighting the synergistic advantages of integrating Chinese and Western medicine throughout the entire perioperative management cycle encompassing "perioperative anti-inflammation, acute analgesia, and chronic rehabilitation." Through systematic literature retrieval and evidence integration, a total of 9 core recommendations were established to provide scientifically sound and clinically practical guidance.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis （UC） mice based on adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor-erythroid 2-related factor 2 （Nrf2） pathway. METHODS Male BALB/c mice were randomly divided into control group， model group， inhibitor group （AMPK inhibitor Compound C 20 mg/kg）， paeoniflorin low-， medium- and high-dose groups （paeoniflorin 12.5， 25， 50 mg/kg）， high- dose of paeoniflorin+inhibitor group （paeoniflorin 50 mg/kg+Compound C 20 mg/kg）， with 8 mice in each group. Except for the control group， mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently， mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally， once a day， for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration， colon length， malondialdehyde （MDA） content， and activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in colon tissues were measured； histopathological morphology of colon tissues， tight junctions between intestinal epithelial cells， and histopathological scoring were all observed and evaluated； the mRNA expressions of AMPK and Nrf2， as well as the protein expressions of heme oxygenase-1（HO-1）， occludin and claudin-1， were all determined in colon tissue. RESULTS Compared with model group， paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue， as well as improved tight junction damage between intestinal epithelial cells. Additionally， significant increases or upregulations were observed in body weight， colon length， activities of SOD and GSH-Px， phosphorylation level of AMPK， and protein expression of Nrf2， HO-1， occludin， claudin-1， and mRNA expressions of AMPK and Nrf2； concurrently， MDA content and histopathological scores were significantly reduced （P＜ 0.05 or P＜0.01）. In contrast， the inhibitor group showed comparable （P＞0.05） or worse （P＜0.05 or P＜0.01） indicators compared to the model group. Conversely， the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin （P＜0.01）. CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice， improve tight junctions between epithelial cells， upregulate the expression of related proteins， and promote the expression and secretion of antioxidant-promoting molecules， thereby ameliorating UC； its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.

ObjectiveTo investigate the effect and mechanism of polysaccharide in water extract of Cyclocarya paliurus （CPWP） in inhibiting benign prostatic hyperplasia （BPH）. MethodsCPWP was obtained by heating reflux， aqueous extraction， alcohol precipitation， and freeze drying. The chemical composition and structural properties of CPWP were analyzed by high performance liquid chromatography with 1-pheny-3-methyl-5-pyrazolone pre-column derivatization and infrared spectroscopy. Male SD rats were randomly assigned into control， model， finasteride （ig 5 mg·kg^-1）， and low-， medium-， and high-dose （ig 50， 75， 100 mg·kg^-1） CPWP groups， with 8 rats in each group. The BPH model was established by subcutaneously injecting propionate testosterone in castrated rats. The rats in the drug intervention groups were administrated with corresponding drugs， and those in the control group were administrated with an equal volume of normal saline each day. After 30 consecutive days， the rats were sacrificed， and the prostate tissue was separated and weighed. The effects of drug interventions on the body weight， prostate wet weight， and prostate index of rats were examined. The prostate tissue was stained with hematoxylin-eosin （HE） for observation of pathological changes. Enzyme-linked immunosorbent assay was employed to measure the level of dihydrotestosterone （DHT）， and immunohistochemical staining was used to detect the expression of steroid 5 alpha-reductase 2 （SRD5A2） and Ki67 in the prostate tissue. ResultsCPWP was identified as a saccharide， with characteristic absorption peaks of saccharides. CPWP showed the total sugar content of 44.15% and molecular weight within the range of 5.5-78.8 kDa， being composed of mannose， rhamnose， galacturonic acid， glucose， galactose， xylose， and arabinose. Compared with the control group， the model group had significantly increased prostate wet weight and prostate index （P<0.01）， thick and tall prostate epithelial cells， increased internal wrinkles， papillary expansion into the cavity， an elevation in DHT level in the serum， and up-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.05， P<0.01）. Compared with the model group， both the finasteride and CPWP groups showed decreases in prostate wet weight and prostate index （P<0.05， P<0.01）， thinned prostate epithelial cells， with only a small portion of internal wrinkles and papillary expansion into the cavity， shortened papillary protrusions， lowered DHT level in the serum， and down-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.01）. Moreover， CPWP exerted effects in a dose-dependent manner. ConclusionCPWP inhibits BPH by regulating the expression of SRD5A2.

Sarcopenia is a clinical syndrome characterized by a decrease in skeletal muscle strength and quality， often accompanied by adverse outcomes such as falls， loss of function and weakness. The pathogenesis of sarcopenia is complex， and studies have shown that dysfunction due to impaired mitochondrial quality control is an important pathological factor in the occurrence and development. Traditional Chinese medicine（TCM） has been widely favoured for regulating mitochondrial homeostasis and preventing sarcopenia by virtue of its multi-target and multi-pathway advantages. They can play a role in the prevention and treatment of sarcopenia by regulating the mitochondrial quality control system to inhibit the occurrence of mitochondrial oxidative stress， regulate the balance of mitochondrial dynamics， inhibit mitochondrial autophagy， promote mitochondrial biosynthesis， resist the occurrence of mitochondrial apoptosis， and maintain the mitochondrial calcium and protein homeostasis. Based on this， the paper reviewed the relationship between mitochondrial quality control and sarcopenia， as well as the mechanism of TCM in intervening the mitochondrial quality control system to treat sarcopenia， in order to provide a new idea for the prevention and treatment of sarcopenia by TCM and to a theoretical basis for the clinical research on TCM intervention in sarcopenia.

AIM: To summarize 10 surgical pearls for managing proliferative diabetic retinopathy(PDR)adapted from the ancient Chinese allusions and analyze the application of these pearls in a real-world fashion.METHODS: Retrospective, noncomparative, interventional study. Ten surgical pearls were summarized and adapted from the ancient Chinese philosophy. Totally 346 cases(443 eyes)that underwent pars plana vitrectomy(PPV)at our hospial from January 2016 to February 2024 were selected. Flexible combinations of these pearls were applied according to the specific condition of each patient during surgeries. The efficacy and safety were analyzed, as well as the application frequencies according to the existence of tractional retinal detachment or not.RESULTS: A total of 473 times of surgeries were performed on all the patients. According to ancient Chinese allusions, ten surgical pearls were summarized from these surgeries. All PPVs went smoothly with the application of different combinations. Finally, almost all proliferative membranes were successfully peeled except for 10 patients(11 eyes), who went through strategy No.10(minimal membranectomy)that, only necessary relaxation incisions were made with most of the proliferative membranes left on purpose. The final visual acuities were mostly improved or stable(1.92±0.83 LogMAR preoperatively vs 1.16±0.85 LogMAR postoperatively, P<0.01). Postoperative complications mainly included early inflammatory responses in the anterior chamber and nuclear sclerosis. Recurrent vitreous hemorrhage, retinal detachment, and hyphema or neovascular glaucoma occurred in 1.9%(9/473), 3.2%(15/473), 0.4%(2/473)and 0.4%(2/473)times of PPVs, respectively. After 12/473(2.5%)times of PPVs, retinal detachment at the macular area still existed, and multiple times of subsequent PPVs were conducted. Final retinal attachment at the macular area was realized in 98.9% eyes. Those 5 unattached eyes were with heavily reproliferated membranes and subsequent tractional retinal detachment recurrence under the oil, and three of them were scleral buckled additionally.CONCLUSION:These 10 surgical strategies and technique pearls were mostly effective and safe in the management of severe PDR patients. They were relatively easy to be memorized and applicated once the meaning of each Chinese idiom was understood. One can use different combinations flexibly according to a patient's specific condition.

Objective: Adolescent depression is a highly prevalent and disabling mental disorder with unclear pathophysiology and unfavorable treatment outcomes. Recent efforts have been focusing on searching for biomarkers as specific indicators of adolescent depression. We performed a systematic literature review and meta-analysis, specifically including studies with healthy control groups as an inclusion criterion. This approach helps to avoid confounding factors and provides more accurate results regarding the inflammatory and immune biomarkers associated with adolescent depression. Methods: Three electronic databases were searched for studies comparing the means and changes in the biomarkers between depressed adolescent patients and healthy controls published in English until February 2024. Two authors independently performed the screening, quality assessment, and data extraction of the studies. A meta-analysis was conducted on outcomes reported by two or more studies using a random-effects model and presented Forrest plots and test statistics (I2) for heterogeneity analysis. Results: Nine studies were included in the review, including seven case-control studies and two cross-sectional studies. These studies included 24 target biomarkers, 13 of which were quantified in 2 or more studies. Compared to the healthy controls, the depressed adolescents had significantly higher values in ten indicators. Additionally, the depressed adolescents had lower procalcitonin levels than the healthy controls. The two groups showed no significant differences in the remaining 13 biomarkers. Conclusion Our findings offer fresh insights into the pathophysiology of inflammatory and immune aspects of adolescent depression and provide helpful guidance in developing targeted and effective intervention and prevention strategies to address adolescent depression.

ObjectiveTo analyze the expression level of triggering receptor expressed on myeloid cells-1 （TREM-1） in serum and ascites of patients with cirrhotic ascites， and to investigate its correlation with clinical features and inflammatory markers and its role in the diagnosis of infection and prognostic evaluation. MethodsA total of 110 patients with cirrhotic ascites who were hospitalized in The Fifth Hospital of Shijiazhuang from January 2019 to December 2020 were enrolled， and according to the presence or absence of intra-abdominal infection， they were divided into infection group with 72 patients and non-infection group with 38 patients. The patients with infection were further divided into improvement group with 38 patients and non-improvement group with 34 patients. Clinical data and laboratory markers were collected from all patients. Serum and ascites samples were collected， and ELISA was used to measure the level of TREM-1. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between indicators. A multivariate Logistic regression analysis was used to identify the influencing factors for the prognosis of patients with cirrhotic ascites and infection. The receiver operating characteristic （ROC） curve was used to evaluate the diagnostic and prognostic efficacy of each indicator， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsThe level of TREM-1 in ascites was significantly positively correlated with that in serum （r=0.50， P<0.001）. Compared with the improvement group， the non-improvement group had a significantly higher level of TREM-1 in ascites （Z=-2.391， P=0.017） and serum （Z=-2.544， P=0.011）， and compared with the non-infection group， the infection group had a significantly higher level of TREM-1 in ascites （Z=-3.420， P<0.001）， while there was no significant difference in the level of TREM-1 in serum between the two groups （P>0.05）. The level of TREM-1 in serum and ascites were significantly positively correlated with C-reactive protein （CRP）， procalcitonin （PCT）， white blood cell count， and neutrophil-lymphocyte ratio （r=0.288， 0.344， 0.530， 0.510， 0.534， 0.454， 0.330， and 0.404， all P<0.05）. The ROC curve analysis showed that when PCT， CRP， and serum or ascitic TREM-1 were used in combination for the diagnosis of cirrhotic ascites with infection， the AUCs were 0.715 and 0.740， respectively. The multivariate Logistic regression analysis showed that CRP （odds ratio ［OR］=1.019， 95% confidence interval ［CI］： 1.001‍ ‍—‍ ‍1.038， P=0.043） and serum TREM-1 （OR=1.002， 95%CI： 1.000‍ ‍—‍ ‍1.003， P=0.016） were independent risk factors for the prognosis of patients with cirrhotic ascites and infection， and the combination of these two indicators had an AUC of 0.728 in predicting poor prognosis. ConclusionThe level of TREM-1 is closely associated with the severity of infection and prognosis in patients with cirrhotic ascites， and combined measurement of TREM-1 and CRP/PCT can improve the diagnostic accuracy of infection and provide support for prognostic evaluation.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*