BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body's cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on"cold stimulation,TRPM8,GLR-3/GluK2 and hypertension"to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.

BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body's cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on"cold stimulation,TRPM8,GLR-3/GluK2 and hypertension"to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.

Objective To investigate the relationship between platelet to lymphocyte ratio(PLR)and low-density lipoprotein cholesterol(LDL-C)/high-density lipoprotein cholesterol(HDL-C)ratio with the degree of carotid artery stenosis,neurological deficits,and prognosis in elderly pa-tients with ischemic stroke and carotid artery stenosis.Methods A total of 186 elderly patients diagnosed with ischemic stroke and carotid artery stenosis admitted in our hospital from June 2021 to June 2024 were enrolled in this study.The PLR and LDL-C/HDL-C ratio were collected,and then with median split,they were divided into high and low PLR groups(both 93 cases),and high and low LDL-C/HDL-C groups(both 93 cases).General clinical data were compared between the two pairs of groups.Multivariate logistic regression analysis was used to identify the factors influencing the severity of carotid artery stenosis,neurological deficits,and prognosis.Kendall's Tau-b correlation analysis was employed to assess the relationship of PLR and LDL-C/HDL-C with the degree of carotid artery stenosis and prognosis.Pearson correlation analysis was conduc-ted to evaluate the association of PLR and LDL-C/HDL-C with neurological deficits.Results Sta-tistically differences were observed in the degree of carotid artery stenosis and prognosis between the high and low PLR groups(P＜0.01).The NIHSS score was significantly higher in the high PLR group(P＜0.01).Similar differences were noted between the high and low LDL-C/HDL-C groups in terms of degree of carotid artery stenosis and prognosis(P＜0.01).The NIHSS score was obviously higher in the high LDL-C/HDL-C group(P＜0.01).Multivariate logistic regression analysis showed that PLR and LDL-C/HDL-C were risk factors for the degree of carotid artery stenosis,neurological deficits and prognosis in elderly patients with carotid artery stenosis after ischemic stroke(OR=3.842,95％CI:2.551-5.328,P=0.000;OR=3.604,95％CI:2.402-5.407,P=0.000;OR=2.956,95％CI:1.955-4.471,P=0.000;OR=3.463,95％CI:2.506-4.785,P=0.000;OR=2.878,95％CI:1.991-4.160,P=0.000;OR=3.785,95％CI:2.483-5.768,P=0.000).Kendall's Tau-b correlation analysis showed that PLR and LDL-C/HDL-C were positively correlated with the degree of carotid artery stenosis and the prognosis in these eld-erly patients(P＜0.05).Pearson correlation analysis indicated that PLR and LDL-C/HDL-C were positively correlated with the NIHSS score in the patients(P＜0.05).Conclusion For the elderly ischemic stroke patients with carotid artery stenosis,PLR and LDL-C/HDL-C are related to the prognosis,and can be used to help assess the severities of carotid artery stenosis and neurological deficits.

Objective To investigate the relationship between platelet to lymphocyte ratio(PLR)and low-density lipoprotein cholesterol(LDL-C)/high-density lipoprotein cholesterol(HDL-C)ratio with the degree of carotid artery stenosis,neurological deficits,and prognosis in elderly pa-tients with ischemic stroke and carotid artery stenosis.Methods A total of 186 elderly patients diagnosed with ischemic stroke and carotid artery stenosis admitted in our hospital from June 2021 to June 2024 were enrolled in this study.The PLR and LDL-C/HDL-C ratio were collected,and then with median split,they were divided into high and low PLR groups(both 93 cases),and high and low LDL-C/HDL-C groups(both 93 cases).General clinical data were compared between the two pairs of groups.Multivariate logistic regression analysis was used to identify the factors influencing the severity of carotid artery stenosis,neurological deficits,and prognosis.Kendall's Tau-b correlation analysis was employed to assess the relationship of PLR and LDL-C/HDL-C with the degree of carotid artery stenosis and prognosis.Pearson correlation analysis was conduc-ted to evaluate the association of PLR and LDL-C/HDL-C with neurological deficits.Results Sta-tistically differences were observed in the degree of carotid artery stenosis and prognosis between the high and low PLR groups(P＜0.01).The NIHSS score was significantly higher in the high PLR group(P＜0.01).Similar differences were noted between the high and low LDL-C/HDL-C groups in terms of degree of carotid artery stenosis and prognosis(P＜0.01).The NIHSS score was obviously higher in the high LDL-C/HDL-C group(P＜0.01).Multivariate logistic regression analysis showed that PLR and LDL-C/HDL-C were risk factors for the degree of carotid artery stenosis,neurological deficits and prognosis in elderly patients with carotid artery stenosis after ischemic stroke(OR=3.842,95％CI:2.551-5.328,P=0.000;OR=3.604,95％CI:2.402-5.407,P=0.000;OR=2.956,95％CI:1.955-4.471,P=0.000;OR=3.463,95％CI:2.506-4.785,P=0.000;OR=2.878,95％CI:1.991-4.160,P=0.000;OR=3.785,95％CI:2.483-5.768,P=0.000).Kendall's Tau-b correlation analysis showed that PLR and LDL-C/HDL-C were positively correlated with the degree of carotid artery stenosis and the prognosis in these eld-erly patients(P＜0.05).Pearson correlation analysis indicated that PLR and LDL-C/HDL-C were positively correlated with the NIHSS score in the patients(P＜0.05).Conclusion For the elderly ischemic stroke patients with carotid artery stenosis,PLR and LDL-C/HDL-C are related to the prognosis,and can be used to help assess the severities of carotid artery stenosis and neurological deficits.

Goniotomy (GT) is a safe and effective type of minimally invasive glaucoma surgery (MIGS) extensively utilized in China.It is particularly suited for treating primary open-angle glaucoma and advanced primary angle-closure glaucoma.Although GT is generally safe, hyphema and postoperative intraocular pressure (IOP) spikes remain common complications after GT.Currently, there is no standardized protocol for managing these issues, which can impact clinicians' assessment of surgical outcomes and potentially affect the prognosis.Therefore, it is crucial to establish comprehensive and detailed management protocols for perioperative hyphema and IOP spike following GT.This will guide clinical practitioners in managing complications appropriately and systematically, thereby promoting the further development and refinement of MIGS.To address these concerns, several domestic glaucoma treatment experts along with members of the Glaucoma Society of Ophthalmology, Guangdong Medical Association reviewed existing literature and held recommendation meetings to develop a guideline for managing perioperative hyphema and IOP spikes following GT.It includes defining perioperative hyphema in GT, discussing its high-risk factors and outcomes, exploring methods for prevention prior to surgery and techniques to reduce bleeding during the procedure, and managing postoperative hemorrhage.Additionally, it covers defining IOP spikes after GT, investigates their causes and contributing factors, and outlines management strategies and anticipated outcomes to provide a valuable resource for clinicians.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

With high incidence, high disability rate and serious impact on patients' quality of life, advanced primary angle-closure glaucoma (PACG) with cataract is a severe eye disease in China and its main treatment method is surgery.Phacoemulsification cataract extraction and intraocular lens implantation (PEI) combined with trabeculectomy has been used to treat advanced PACG with cataract, but there are many postoperative complications.Recently, combined PEI, goniosynechialysis (GSL) and goniotomy (GT) has been proven to be a safe and effective surgical treatment for advanced PACG with cataract.At present, the combined PEI+ GSL+ GT surgery has been widely applied, but there is still a lack of uniform standards for its clinical application.Therefore, it is necessary to formulate a detailed and complete recommendation of the surgical procedures for PEI+ GSL+ GT, to standardize its application in clinical practice.Based on the analysis of the existing problems, some glaucoma experts in China have formulated detailed and complete operation norms, as well as expert recommendations on surgical indications and contraindications, anesthetic methods, surgical techniques and perioperative medication to standardize the application process of PEI+ GSL+ GT in clinical practice.

Minimally invasive glaucoma surgery (MIGS) has been successfully incorporated in clinical practice in recent years.Increasing evidence shows that MIGS also plays an increasingly important role in the treatment of primary angle-closure glaucoma (PACG). Surgical peripheral iridectomy (SPI) plus goniosynechialysis (GSL) and goniotomy (GT), as a new procedure, has been proven to be safe and effective in the treatment of PACG with no or mild cataracts.However, there is still a lack of uniform standards for indications, surgical procedures, and perioperative medication.Therefore, it is necessary to formulate a detailed and complete expert recommendations on surgical procedures to standardize the application of combined SPI+ GSL+ GT in the treatment.Some experts in glaucoma treatment and management in China have discussed the current problems and developing trend in MIGS for PACG and put forward the expert recommendations of standard process, including indications, anaesthetic methods, surgical site, operating procedure and rational administration of drugs in perioperation, in order to standardize the medical process of clinicians using combined SPI+ GSL+ GT in PACG treatment and lay a foundation for better evaluation of the efficacy of MIGS.

Objective:To evaluate the preliminary effectiveness and safety of surgical peripheral iridectomy (SPI) combined with goniosynechilysis (GSL) and goniotomy (GT) in the treatment of advanced primary angle-closure glaucoma (PACG).Methods:A multicenter observational case series study was performed.Thirty-five eyes of 27 patients with advanced PACG, who underwent SPI+ GSL+ GT with a follow-up of at least 6 months, were included from August 2021 to January 2022 at Zhongshan Ophthalmic Center, Handan City Eye Hospital, Shijiazhuang People's Hospital, West China Hospital of Sichuan University, and the Third Affiliated Hospital of Chongqing Medical University.The mean follow-up time was 9(7, 10) months.Pre- and post-operative best corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured with an ETDRS chart and a Goldmann applanation tonometer, respectively.The number of anti-glaucoma medications applied before and after surgery was recorded, and the complications after surgery were analyzed.Success rate of surgery was calculated.Complete surgical success was defined as an IOP of 5-18 mmHg (1 mmHg=0.133 kPa) and 20% reduction from baseline without anti-glaucoma medication or reoperation.Qualified success was defined as achieving criterion of complete success under anti-glaucoma medications.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2021KYPJ177). Written informed consent was obtained from each subject.Results:The mean preoperative IOP was (30.83±8.87)mmHg, which was significantly decreased to (15.69±3.70)mmHg at 6 months after the surgery ( t=8.588, P<0.001), with a 44.00% (34.78%, 60.00%) decline of 13.00(8.00, 21.00)mmHg.The median number of anti-glaucoma medications was significantly reduced from 2(0, 3) preoperatively to 0 (0, 1) postoperatively ( Z=-3.659, P<0.001). The mean preoperative and postoperative 6-month BCVA were 0.80(0.63, 1.00) and 0.80(0.60, 1.00), respectively, showing no significant difference ( Z=-0.283, P=0.777). Complete surgical success rate was 62.86%(22/35), and the qualified success rate was 91.43%(32/35). Surgical complications mainly included hyphema (6/35), IOP spike (3/35), and shallow anterior chamber (4/35). There was no vision-threatening complication. Conclusions:SPI+ GSL+ GT is preliminarily effective and safe in the treatment of advanced PACG, which provides a new option for PACG.