AIM: To assess the stability of the tear film and the characteristics of corneal nerves in patients with Parkinson's disease(PD).METHODS: This cross-sectional observational study included 72 PD patients and 50 healthy controls. Disease severity was determined using the Hoehn-Yahr(H-Y)scale, dividing patients into mild and moderate PD groups. Dry eye symptoms were evaluated via the ocular surface disease index(OSDI)questionnaire, while tear secretion was quantified using the Schirmer I test. Ocular surface damage was assessed through staining scores, and comprehensive ocular examinations were performed utilizing the LipiView ocular surface interferometer and an ocular surface analyzer. Corneal nerve parameters were examined using corneal confocal microscopy in conjunction with automated analysis software ACCMetrics, with correlations drawn between these parameters, PD course, and severity.RESULTS: PD patients exhibited significantly elevated OSDI scores, indicative of more pronounced dry eye symptoms compared to the control group(F=70.290, P<0.01). Tear film stability was markedly compromised, with significantly shorter tear film breakup time and increased corneal fluorescein staining, both showing statistically significant differences relative to controls(all P<0.01). Tear secretion indices, including Schirmer I test results and tear meniscus height, were significantly reduced in PD patients(all P<0.01), whereas lipid secretion indices, such as lipid layer thickness and meibomian gland dropout score, did not show significant variation. Corneal nerve analysis revealed significant reductions in corneal nerve fiber density, nerve branch density, fiber length, and total branch density in PD patients compared to controls(all P<0.01). Furthermore, blink frequency was markedly prolonged(F=62.353, P<0.01). Correlation analysis demonstrated a significant relationship between alterations in tear film stability and both disease duration and H-Y scores.CONCLUSION: PD patients have obvious dry eye manifestations in the early stage of the disease, including the reduction of tear film stability and corneal nerve fiber density, and gradually aggravate with the progress of the disease. Neurodegenerative disease-related dry eye needs to be diagnosed early and actively treated.

ObjectiveTo explore the mechanism of Shaoyaotang in the prevention and treatment of colitis-associated carcinogenesis （CAC） based on myeloid-derived suppressor cells （MDSCs）-related immunosuppressive microenvironment. MethodsA total of 140 six-week-old SPF FVB male mice were randomly divided into seven groups： Blank group， Shaoyaotang without model group （7.12 g·kg^-1）， model group， sulfasalazine group （0.52 g·kg^-1）， Shaoyaotang low-dose group （3.56 g·kg^-1）， Shaoyaotang medium-dose group （7.12 g·kg^-1） and Shaoyaotang high-dose group （14.24 g·kg^-1）， with 20 mice in each group. The blank control group and the Shaoyaotang without model group received a single intraperitoneal injection of physiological saline （10 mg·kg^-1）， while the other five groups were given a single intraperitoneal injection of azoxymethane （AOM） （10 mg·kg^-1）. After 1 week， the mice were given drinking water containing 2% dextran sulfate sodium （DSS） for 1 week， followed by normal drinking water for 2 weeks. This cycle was repeated three times over a total period of 14 weeks to establish the CAC mouse model. Each group was administered gavage once daily for 2 weeks starting on the 14^th day of the experiment， followed by three times a week until the end of the experiment. The body weight of the mice was recorded weekly. Mice were sacrificed on the 28^th and 98^th days of the experiment. After dissection， the colon length， colon weight， spleen weight， tumor size， and tumor number were measured. Hematoxylin and eosin （HE） staining was used to assess the pathological morphology of colon tumor tissue. Flow cytometry was used to detect MDSCs， regulatory T cells （Tregs）， CD4⁺ T cells， CD8⁺ T cells， and the CD4⁺/CD8⁺ T cell ratio in the spleen. Immunohistochemistry was used to detect the expression levels of programmed cell death protein-1 （PD-1）， programmed cell death ligand 1 （PD-L1）， phosphorylated AMP-activated protein kinase （p-AMPK）， phosphorylated nuclear factor-κB （p-NF-κB）， and hypoxia-inducible factor 1α （HIF-1α） in the colon tissue. ResultsOn day 14， compared with the blank group， the body weight of the model group was significantly reduced （P<0.01）， reaching its lowest point on day 28 （23.39 ± 0.95 ） g. On days 28 and 98， compared with the blank group， the colon length in the model group was significantly shortened （P<0.01）， the colon index significantly increased （P<0.01）， the spleen index significantly increased （P<0.01）， and the tumor load significantly increased （P<0.01）. HE staining showed that in the model group， tumor cells， a large number of inflammatory cell infiltrates， goblet cell disappearance， and crypt loss were observed. In each dose group of Shaoyaotang， the damage to the colonic mucosa， inflammatory cell infiltration， and crypt structure destruction were alleviated. Compared with the model group， the body weight of mice in each dose group of Shaoyaotang increased. On day 98， the colon length was significantly increased （P<0.01）， the colon index significantly decreased （P<0.01）， the spleen index significantly decreased （P<0.01）， and the tumor burden significantly decreased （P<0.01） in each Shaoyaotang dose group. On days 28 and 98， MDSCs and Tregs in the spleen of the medium- and high-dose Shaoyaotang groups were significantly reduced （P<0.01）， while CD4⁺ T cells and the CD4⁺/CD8⁺ T cell ratio were significantly increased （P<0.01）. The proportion of CD8⁺ T cells in the spleen and the expression levels of PD-1 and PD-L1 in the colon tissues of mice in each Shaoyaotang dose group were significantly increased to varying degrees （P<0.05， P<0.01）. On days 28 and 98， the expression of p-AMPK-positive cells in the colon tissue of the medium- and high-dose Shaoyaotang groups was significantly increased （P<0.01）， while the expression of p-NF-κB and HIF-1α was significantly reduced （P<0.01）. ConclusionShaoyaotang can regulate MDSC recruitment and modulate the immune function of T lymphocyte subsets to inhibit the occurrence and development of AOM/DSS-induced CAC in mice. The mechanism may be related to the activation of the AMPK/NF-κB/HIF-1α pathway.

OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China， providing a reference for promoting enterprise R&D and production， as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval， Pharnexcloud biomedical database， and National Medical Insurance Drug Directory， this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30， 2024， a total of 68 pediatric medicines had been approved through the priority review and approval process， covering 12 therapeutic areas， with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days， with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years， with an average of 1.42 years. This included 12 domestic new medicines， 21 domestic generic medicines， 35 imported medicines， as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally， 31 of these medicines had been included in the medical insurance catalog， representing a proportion of 45.59%. CONCLUSIONS Currently， a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding， and the dosage forms are becoming more tailored to children’s needs. However， there are still issues such as slow progress in new medicine development， insufficient stability in the medicine review and approval process， and a need to increase the proportion of medicines included in medical insurance.

This study examined the effect of islet macrophages on β-cell function changes during type 2 diabetes mellitus (T2DM) progression based on the traditional Chinese medicine theory that " moderate fire generating qi, hyperactive fire consuming qi" . T2DM is closely associated with chronic low-grade inflammation, with islet macrophages playing a central role in this process. Under physiological conditions, islet macrophages secrete anti-inflammatory and growth factors to regulate the immune response, promote cell proliferation, and support islet β-cell survival and function, reflecting the concept of " moderate fire generating qi" . However, during the pathological process of T2DM, islet macrophages become over-activated and dysfunctional, secreting large amounts of pro-inflammatory factors that trigger severe inflammatory responses and oxidative stress. This process damages islet β-cells, disrupts the islet microenvironment and blood supply, exacerbates local inflammation and structural damage, and worsens the survival environment of β-cells. Ultimately, this leads to fewer β-cells and function loss, aligning with the " hyperactive fire consuming qi" theory, where excessive fire depletes qi and blood. This study enhances the understanding and application of traditional Chinese medicine theories in modern medicine, offering a new perspective on T2DM prevention and treatment. Regulating islet macrophage function and reducing their pro-inflammatory responses may become key strategies for preserving β-cell function and slowing T2DM progression.

Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death （PCD） is a kind of regulable cell death including various forms such as apoptosis， autophagy， pyroptosis， necrosis， and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years， modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation， PCD can control tumor development in time by playing a specific immune clearance role， while in the later tumorigenic stage， PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment， resulting in carcinogenic effects. Therefore， PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui， the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins''， the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis， while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis， which led to the escape and development of tumor cells. Therefore， under the guidance of ''regulating Qi and removing toxins''， the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation， the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage， the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells， with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.

Tumor immune homeostasis is a dynamic equilibrium state in which the body removes abnormal mutated cells in time to prevent tumor development without damaging other normal cells under the surveillance of the immune system. It is an important concept to understand the process of tumor development. Programmed cell death （PCD） is a kind of regulable cell death including various forms such as apoptosis， autophagy， pyroptosis， necrosis， and ferroptosis. It is regarded as an important way for the body to remove abnormal or mutated cells. In recent years， modern research has found that PCD has a bi-directional regulatory effect on carcinogenesis and tumor development. In the early stage of tumor formation， PCD can control tumor development in time by playing a specific immune clearance role， while in the later tumorigenic stage， PCD can promote the growth and development of tumor cells by forming a tumor-specific microenvironment， resulting in carcinogenic effects. Therefore， PCD is regarded as an important way to maintain tumor immune homeostasis. Based on the idea of ''supporting the vital Qi and cultivating the root'' by professors Yu Guiqing and Piao Bingkui， the team proposed the theory of ''regulating Qi and resolving toxins'' and applied it to clinical tumor prevention and treatment. Based on the theory of ''regulating Qi and resolving toxins''， the research summarized the current progress of modern medical research on mechanisms related to PCD to explore the role of PCD in the regulation of tumor immune homeostasis. The article believed that the harmonious state of Qi movement was the basic condition for normal PCD to maintain tumor immune homeostasis， while the disorder of Qi movement and the evolution of tumor toxicity were the core processes of abnormal PCD and disorder of tumor immunity homeostasis， which led to the escape and development of tumor cells. Therefore， under the guidance of ''regulating Qi and removing toxins''， the idea of full-cycle prevention and treatment of tumors was proposed summarily. In the early stage of tumor formation， the method of ''regulating Qi movement and strengthening vital Qi'' was applied to reestablish tumor immune homeostasis and to promote the elimination of abnormal cells. In the late tumorigenic stage， the method of ''resolving toxins and dispelling evils'' was applied to reverse the specific microenvironment of tumors and inhibit the development of tumor cells， with a view to providing new theoretical support for the prevention and treatment of tumors through traditional Chinese medicine.

In recent years， diabetic nephropathy （DN） has become an increasingly serious health challenge worldwide， and its morbidity and mortality rates are rapidly increasing. The patients suffering from the disease tend to be younger. DN is not only accompanied by a wide range of renal pathological changes， such as renal hypertrophy， inflammatory cell infiltration， expansion of the tethered membrane stroma， and thickening of the basement membrane but is also the main cause of end-stage renal disease and death in patients with diabetes mellitus. Therefore， it is particularly urgent to explore new strategies for the prevention and treatment of DN. The pathogenesis of DN is intricate and complex， with current research focusing on multifactorial interactions between metabolic and hemodynamic factors， such as hypoxia， inflammatory responses， and fibrotic processes. Notably， hypoxia plays a pivotal role in the initiation and progression of DN. Hypoxia-inducible factor （HIF-1α）， as a key regulatory protein commonly found in hypoxic cells， has a profound impact on various physiological and pathological processes， such as cell metabolism， vascular neogenesis， oxidative stress， and apoptosis. With its unique theoretical system and therapeutic approach， traditional Chinese medicine has demonstrated significant advantages in coping with hypoxic diseases and can slow down the progression of DN by regulating the expression level of HIF-1α and its downstream signaling molecules and exerting anti-inflammatory， antioxidant， and antifibrotic effects， which has positive clinical significance for drug development and early prevention and treatment of DN.

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.