A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Myocardial fibrosis （MF）， characterized by decreased cardiac function and myocardial compliance， is a pathological process and a progression factor in various cardiovascular diseases. The nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome is closely related to the development of MF. Recent studies have shown that traditional Chinese medicine （TCM） can regulate the NLRP3 inflammasome to alleviate MF. Based on this， this article systematically summarizes the research progress on the mechanisms by which TCM regulates the NLRP3 inflammasome to improve MF. It is found that active ingredients of TCM， such as alkaloids （lycorine，vincristine，bufalin）， saponins （astragaloside Ⅳ， diosgenin，ginsenoside Rg3）， terpenoids （celastrol，oridonin）， and phenols （polydatin，curcumin，phloridzin） as well as TCM formulas （Zhachong shisanwei pills，Zhilong huoxue tongyu capsules， Luqi formula） can inhibit the activation of the NLRP3 inflammasome， thereby suppressing the release of inflammatory factors such as interleukin-1β and IL-18， reducing inflammatory damage to myocardial tissue， alleviating excessive deposition of the extracellular matrix， and thus exerting the effect of improving MF.

Huaihuasan， first recorded in Experiential Prescriptions for Universal Relief （Pu Ji Ben Shi Fang）， is a classic prescription for the treatment of ''hematochezia due to intestinal wind''. In 2018， it was included by the National Administration of Traditional Chinese Medicine as one of the first 100 classic prescriptions. This formula consists of four ingredients， i.e.， Sophorae Flos， Platycladi Cacumen， Schizonepetae Spica， and Aurantii Fructus. It is known for its ability to clear the intestines， dispel wind， cool the blood， and stop bleeding. In modern clinical practice， Huaihuasan， often with modifications， is widely used to treat various digestive tract diseases， including ulcerative colitis （UC）， with significant long-term effects. UC is a chronic， non-specific inflammatory bowel disease. Currently， Western medicine primarily treats UC with glucocorticoids， aminosalicylates， and immunosuppressants， which have good short-term efficacy but numerous adverse reactions， high recurrence rates， and the need for lifelong medication. Modern clinical studies have shown that Huaihuasan can significantly improve symptoms of UC， such as abdominal pain and diarrhea， reduce disease activity scores （Sutherland）， promote intestinal mucosal healing， alleviate anxiety and depression， and significantly improve the quality of life of patients. Pharmacological studies have shown that the main active components of Huaihuasan include quercetin， rutin， kaempferol， naringenin， and volatile oils. These compounds exert their effects by inhibiting inflammatory responses and protecting the intestinal mucosal barrier. They also exhibit antioxidant properties and regulate various signaling pathways， including tumor necrosis factor-α （TNF-α）， interleukin-2 （IL-2）， interleukin-4 （IL-4）， interleukin-1β （IL-1β）， monocyte chemoattractant protein-1 （MCP-1）， nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， and the KRAS-regulated mitogen-activated protein kinase （MEK）-extracellular signal-regulated kinase （ERK） pathway. These multi-target pathways improve UC symptoms， inhibit inflammation-cancer transition， and help maintain intestinal homeostasis. However， the precise mechanism of action has not yet been systematically elucidated. This paper reviews the research progress on Huaihuasan and main ingredients from its component drugs， focusing on their effects against UC. It also discusses current research limitations and suggests strategies for improvement， aiming to provide a reference for further studies on Huaihuasan in the treatment of UC and the development of new drugs.

Cardiovascular disease (CVD) is the leading cause of death worldwide. As the key pathological basis of CVD, arteriosclerosis holds great significance for early screening. However, existing clinical and homecare detection devices have many shortcomings; for instance, the commonly used non-invasive indicator PWV (pulse wave velocity) is easily interfered by blood pressure.This study developed a homecare arteriosclerosis monitoring system, which integrates the measurement functions of cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI). The hardware design of the system includes an integrated structure of flexible silver ion electrodes and clip-type cuffs, a contact heart sound sensor, and a stepped deflation blood pressure measurement module. Meanwhile, a high-precision analog-to-digital conversion module and the STM32F405 main control chip are used to realize the synchronous acquisition of multiple signals.In terms of software, the underlying driver program was designed through MDK (Keil5), and a user interface was built on the Visual Studio platform to achieve functions such as data acquisition, display, and storage. At the algorithm level, the system adopted algorithms like the Pan-Tompkins algorithm to identify key feature points of physiological signals, and then calculate CAVI and ABI.System test results show that the ECG input noise of the system is less than 20 μV, the common-mode rejection ratio is 95 dB, and the blood pressure measurement error does not exceed 2 mmHg, which meets the design goals. Clinical data analysis indicates that CAVI is highly positively correlated with pulse wave velocity (PWV) ( r=0.85, P<0.001), but CAVI is less affected by blood pressure fluctuations. In addition, with the increase of risk factors (such as hypertension, hyperlipidemia, coronary heart disease, etc.) and age, arteriosclerosis indicators (CAVI, PWV, ABI) all show an upward trend.In conclusion, the homecare arteriosclerosis monitoring system proposed in this study not only overcomes the problems of traditional devices that rely on professional operation and are susceptible to blood pressure interference, but also provides a reliable tool for arteriosclerosis screening in home scenarios, and has important reference value for clinical diagnosis.
Humans ; Cardio Ankle Vascular Index ; Home Care Services ; Atherosclerosis/diagnosis* ; Ankle Brachial Index ; Algorithms ; Pulse Wave Analysis ; Arteriosclerosis/diagnosis* ; Monitoring, Physiologic/instrumentation*

Hepatic ischemia-reperfusion injury (HIRI) has been considered as an inevitable process of liver transplantation. Hepatocyte ferroptosis is a key factor in HIRI development, yet precise mechanism and potential therapies are still unclear. Here, we demonstrated a strong correlation between hepatocyte ferroptosis and the downregulation of poly(rC)-binding protein (PCBP2), which compromised the stability of antiporter system Xc^- (consisted of SL3A2/SLC7A11). Besides, inhibiting PCBP2 contributed to facilitating cofactor p300 to enhance the transcriptional activity of HIF1α, leading to the expression and secretion of HMGB1. Then, released HMGB1 from ferroptotic hepatocytes worsened M1 macrophage recruitment and immune response during HIRI. Additionally, acteoside (ACT) was shown to assist PCBP2 in stabilizing the mRNA stability of Slc3a2 and Slc7a11, as well as enhance the binding affinity of PCBP2-system Xc^-. Beyond that, ACT also supported PCBP2 to limit HMGB1-induced M1 macrophage recruitment through imposing restrictions on p300 and HIF1α. Furthermore, specific knockdown of PCBP2 in hepatocytes directly interposed the therapeutic efficacy of ACT on HIRI mice. In conclusion, ACT alleviated hepatocyte ferroptosis and HIRI via promoting PCBP2 to maintain the stability of system Xc^- and limit HIF1α/p300-HMGB1 signaling. These findings highlight the therapeutic benefits of ACT in treating HIRI and offer insights into innovative therapeutic strategies.

Drug addiction, a disorder characterized by chronic relapse and compulsive drug use, poses a significant threat to public safety and human health. Addictive substances can be categorized as natural, semi-synthetic, or synthetic based on their origin. Additionally, they can be classified into three groups according to their pharmacological targets: opioids, hallucinogens, and cannabinoids that act on G-protein-coupled receptors (GPCRs); alcohols, nicotine, ketamine, barbiturates, and benzodiazepines (BDZs) that affect ligand-gated ion channel-type receptors; and psychostimulants that interact with monoamine transporters. Current treatments for drug addiction primarily include substitution therapy and non-pharmacological approaches. However, these methods have limitations, particularly in addressing the underlying causes of relapse. Several drugs in clinical trials have demonstrated potential therapeutic effects for addiction to opioids, heroin, cocaine, and other substances. This review examines the origins and pharmacological mechanisms of addiction to naturally-derived psychoactive substances (NPS) and provides an overview of recent advancements in pharmacotherapy for drug addiction.
Humans ; Substance-Related Disorders/drug therapy* ; Psychotropic Drugs/therapeutic use* ; Animals

Major depressive disorder (MDD) has become an increasingly serious public health issue, characterized by high incidence and high disability rates. It often coexists with other mental health problems and physical diseases, with a significant negative impact on patients' quality of life. In clinical practice, MDD is considered a heterogeneous disease. The complexity of the pathological mechanisms and the variability in treatment responses lead to a lack of clear therapeutic targets, which complicates the treatment process. In recent years, with advancements in neuroscience, the crucial role of microglia in the pathogenesis of MDD has been revealed. As the main immune cells in the brain, microglia are not only involved in the regulation of neuroinflammation but also play important roles in neurogenesis and neuronal regulation in MDD. This article mainly discusses the role of microglia in the pathophysiological mechanisms of MDD, aiming to provide a theoretical basis for microglia as a potential target for the treatment of MDD.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.

AIM: To explore the variance in efficacy between botulinum toxin A(BTA)injection and extraocular muscle surgery in managing large-angle(≥+60 PD)acute acquired concomitant esotropia(AACE).METHODS: A retrospective analysis was conducted on clinical data of 60 patients with AACE treated at our hospital from June 2020 to December 2022. Patients were divided into three groups based on different treatments: 2.5 IU BTA injection group(14 cases), 5.0 IU BTA injection group(29 cases), and surgical group(17 cases). Follow-up was conducted for 6 mo after treatment to observe the degree of strabismus after the correction of refractive error, visual function, treatment effectiveness, and occurrence of complications after BTA injection.RESULTS: At 6 mo post-treatment, the degree of strabismus in the surgical group and the 5.0 IU BTA injection group was lower than that in the 2.5 IU BTA injection group(P<0.017). However, there was no significant difference in the degree of strabismus between the surgical group and the 5.0 IU BTA injection group(P>0.017). The effective rate of the 5.0 IU BTA injection group was higher than that of the 2.5 IU BTA injection group(86% vs 43%, P<0.017). There was no difference in visual function among the three groups(P>0.05). The incidence of complications after treatment was not significantly different between the 2.5 IU BTA injection group and the 5.0 IU BTA injection group(43% vs 52%, P>0.05).CONCLUSION: For AACE patients with esotropia degree ≥+60 PD, bilateral medial rectus injection of 5.0 IU BTA can yield outcomes comparable to traditional extraocular muscle surgery, with the advantages of minimal trauma and simple and convenient operation.