Skin wound repair is critically regulated by peripheral nerves. Injury or dysfunction of these nerves represents a key factor impairing the healing of pathological wounds, such as diabetic ulcers and deep burns. The mechanisms by which peripheral nerves participate in cutaneous wound healing primarily involve modulation of immune responses, construction of stem cell niches, and promotion of angiogenesis. Sensory neurons initiate and mediate essential local immune responses, contribute to the epidermal stem cell microenvironment, and support regenerative potential. Sympathetic nerves bidirectionally regulate immune homeostasis via the release of various neuromodulators and precisely control the activation of hair follicle stem cells as well as the homeostasis of melanocyte stem cells. Schwann cells also play pivotal roles in immune modulation, balancing repair processes and mitigating scar formation. During revascularization, sensory and autonomic nerve terminals release neurotransmitters that precisely regulate vasomotor activity and angiogenesis, while Schwann cells facilitate the reconstruction of functional vascular networks via potent paracrine signaling. This review systematically summarizes the crucial roles of peripheral nerves in skin wound repair, with emphasis on their regulatory mechanisms in immune responses, stem cell activation and homeostasis, and vascular dynamics, thereby providing insights into the development of novel therapeutic strategies targeting peripheral nerve regulation.
Humans ; Wound Healing/physiology* ; Peripheral Nerves/physiology* ; Schwann Cells/physiology* ; Skin/injuries* ; Animals

Objective:To investigate the effects of exercise preconditioning on hippocampal microglia polarization and my-elin loss in vascular dementia(VD)model rats.Method:Sixty male SPF SD rats were randomly divided into sham group,model group,exercise precondition-ing sham group and exercise preconditioning model group,with 15 rats in each group.The exercise precondi-tioning rats was trained in weightless swimming exercise for 4 weeks(5sessions/week,30min/session)before mod-eling.The VD model was established by bilateral common carotid artery ligation.Behavioral tests were conduct-ed using the Morris water maze,and the demyelination in the CA1 region of the hippocampus was observed by Luxol fast blue staining.The polarization of microglia in the CA1 region of the hippocampus was observed by immunofluorescence double labeling staining,and the contents of interleukin 4(IL-4),interleukin 10(IL-10),interleukin-1 beta(IL-1β),and tumor necrosis factor-α(TNF-α)in the serum were detected by ELISA.Result:Four weeks after modeling,the average escape latency of rats in the model group was prolonged and the number of platform crossings was reduced compared with the sham group(P<0.05);the average escape laten-cy of rats in the exercise preconditioning model group was prolonged and the number of platform crossings was reduced compared with the exercise preconditioning sham group(P<0.05);the escape latency of rats in the model group was prolonged compared with the exercise preconditioning model group(P<0.05).The histological demyelination score showed that compared with the sham group,the demyelination in the model group was in-creased(P<0.05);the demyelination in the exercise preconditioning model group was increased compared with the exercise preconditioning sham group(P<0.05);the demyelination in the model group was increased compared with the exercise preconditioning model group(P<0.05).Compared with the sham group,the expression of in-ducible nitric oxide synthase(iNOS)protein in the CA1 region of the hippocampus in the model group was in-creased,while the expression of arginase1(Arg1)protein was decreased(P<0.05).Compared with the exercise preconditioning sham group,the expression of iNOS protein in the CA1 region of the hippocampus in the exer-cise preconditioning model group was significantly increased(P<0.05),while the expression of Arg-1 protein was significantly decreased(P<0.05).Compared with the exercise preconditioning model group,the expression of iN-OS protein in the CA1 region of the hippocampus in the model group was increased,while the expression of Arg1 protein was decreased(P<0.05).Compared with the sham group,the contents of IL-4 and IL-10 in the se-rum of rats in the model group decreased,while the contents of IL-1β and TNF-α increased(P<0.05).Compared with the exercise preconditioning sham group,the contents of IL-4 and IL-10 in the serum of rats in the exer-cise preconditioning model group decreased,while the contents of IL-1β and TNF-α increased(P<0.05).Com-pared with the exercise preconditioning model group,the content of IL-4 in the serum of rats in the model group decreased,while the content of IL-1β increased(P<0.05).Conclusion:Exercise preconditioning can promote microglial M2 polarization and myelin fragment phagocyto-sis,inhibit hippocampal nerve inflammation,and improve the learning and memory ability of rats with vascu-lar dementia.

Corneal neovascularization(CNV)is a pathological condition characterized by the invasion of new blood vessels into the normally avascular corneal area from the corneal periphery,leading to severe vision loss and potentially blindness.Currently,surgical,physical,and pharmacological therapies are the main clinical approaches for treating CNV.Surgical treatment aims to remove abnormal vascular tissue or perform corneal trans-plantation to inhibit angiogenesis;however,it carries a risk of postoperative rejection.Physical therapy involves the direct application of non-invasive modalities,such as laser treatment,to the neovascularized area to suppress vascular growth.Nevertheless,this approach may cause damage to surrounding healthy tissues.Pharmacotherapy has recently become a research hotspot in CNV treatment due to its convenient administration.Clinically,the drugs used for CNV treatment mainly include anti-inflammatory agents,anti-VEGF drugs,and immunosuppressants,which inhibit CNV progression by targeting angiogenesis-related signaling pathways.However,these drugs often lead to drug resistance and toxic side effects.Therefore,there is an urgent need to develop more effective and safer therapeutic agents for CNV.This article reviews the current clinical treatment status of CNV and highlights recent advances in the use of small molecule extracts from traditional Chinese medicine for CNV therapy,aiming to provide potential candidate drugs and a scientific theoretical basis for clinical management of CNV.

The complement component 4 binding protein alpha(C4BPA)gene is the alpha chain of complement binding protein 4.As a plasma protein involved in the complement and coagulation systems,it can influence immune responses and lipid metabolism.In order to study the polymor-phism of C4BPA gene and its correlation with milk quality traits in Chinese Holstein cows,genom-ic DNA was extracted from blood samples of 92 Chinese Holstein cows,and the target fragment of C4BPA gene was amplified by PCR,and the association analysis was performed by using direct se-quencing to obtain the SNP loci and milk quality traits.The results showed that among the four SNPs found at the third intron of the C4BPA gene,I3-11 G＞A was highly significantly correlated with milk protein and urea nitrogen(P＜0.05),I3-291 T＞G was significantly correlated with lac-tose(P＜0.05),I3-374 C＞T was highly significantly correlated with lactose and urea nitrogen(P＜0.05),and I3-375 T＞G was highly significantly correlated with lactose(P＜0.05),milk pro-tein and urea nitrogen.The chi-square test values for each point indicated that the population was in genetic equilibrium.Individuals of haplotype combination H1 H1 had the highest lactose content,and haplotype combination H1H2 can be used as the best haplotype combination in the molecular selection work of dairy cows.

Objective:To investigate the effects of exercise preconditioning on hippocampal microglia polarization and my-elin loss in vascular dementia(VD)model rats.Method:Sixty male SPF SD rats were randomly divided into sham group,model group,exercise precondition-ing sham group and exercise preconditioning model group,with 15 rats in each group.The exercise precondi-tioning rats was trained in weightless swimming exercise for 4 weeks(5sessions/week,30min/session)before mod-eling.The VD model was established by bilateral common carotid artery ligation.Behavioral tests were conduct-ed using the Morris water maze,and the demyelination in the CA1 region of the hippocampus was observed by Luxol fast blue staining.The polarization of microglia in the CA1 region of the hippocampus was observed by immunofluorescence double labeling staining,and the contents of interleukin 4(IL-4),interleukin 10(IL-10),interleukin-1 beta(IL-1β),and tumor necrosis factor-α(TNF-α)in the serum were detected by ELISA.Result:Four weeks after modeling,the average escape latency of rats in the model group was prolonged and the number of platform crossings was reduced compared with the sham group(P<0.05);the average escape laten-cy of rats in the exercise preconditioning model group was prolonged and the number of platform crossings was reduced compared with the exercise preconditioning sham group(P<0.05);the escape latency of rats in the model group was prolonged compared with the exercise preconditioning model group(P<0.05).The histological demyelination score showed that compared with the sham group,the demyelination in the model group was in-creased(P<0.05);the demyelination in the exercise preconditioning model group was increased compared with the exercise preconditioning sham group(P<0.05);the demyelination in the model group was increased compared with the exercise preconditioning model group(P<0.05).Compared with the sham group,the expression of in-ducible nitric oxide synthase(iNOS)protein in the CA1 region of the hippocampus in the model group was in-creased,while the expression of arginase1(Arg1)protein was decreased(P<0.05).Compared with the exercise preconditioning sham group,the expression of iNOS protein in the CA1 region of the hippocampus in the exer-cise preconditioning model group was significantly increased(P<0.05),while the expression of Arg-1 protein was significantly decreased(P<0.05).Compared with the exercise preconditioning model group,the expression of iN-OS protein in the CA1 region of the hippocampus in the model group was increased,while the expression of Arg1 protein was decreased(P<0.05).Compared with the sham group,the contents of IL-4 and IL-10 in the se-rum of rats in the model group decreased,while the contents of IL-1β and TNF-α increased(P<0.05).Compared with the exercise preconditioning sham group,the contents of IL-4 and IL-10 in the serum of rats in the exer-cise preconditioning model group decreased,while the contents of IL-1β and TNF-α increased(P<0.05).Com-pared with the exercise preconditioning model group,the content of IL-4 in the serum of rats in the model group decreased,while the content of IL-1β increased(P<0.05).Conclusion:Exercise preconditioning can promote microglial M2 polarization and myelin fragment phagocyto-sis,inhibit hippocampal nerve inflammation,and improve the learning and memory ability of rats with vascu-lar dementia.

The complement component 4 binding protein alpha(C4BPA)gene is the alpha chain of complement binding protein 4.As a plasma protein involved in the complement and coagulation systems,it can influence immune responses and lipid metabolism.In order to study the polymor-phism of C4BPA gene and its correlation with milk quality traits in Chinese Holstein cows,genom-ic DNA was extracted from blood samples of 92 Chinese Holstein cows,and the target fragment of C4BPA gene was amplified by PCR,and the association analysis was performed by using direct se-quencing to obtain the SNP loci and milk quality traits.The results showed that among the four SNPs found at the third intron of the C4BPA gene,I3-11 G＞A was highly significantly correlated with milk protein and urea nitrogen(P＜0.05),I3-291 T＞G was significantly correlated with lac-tose(P＜0.05),I3-374 C＞T was highly significantly correlated with lactose and urea nitrogen(P＜0.05),and I3-375 T＞G was highly significantly correlated with lactose(P＜0.05),milk pro-tein and urea nitrogen.The chi-square test values for each point indicated that the population was in genetic equilibrium.Individuals of haplotype combination H1 H1 had the highest lactose content,and haplotype combination H1H2 can be used as the best haplotype combination in the molecular selection work of dairy cows.

Corneal neovascularization(CNV)is a pathological condition characterized by the invasion of new blood vessels into the normally avascular corneal area from the corneal periphery,leading to severe vision loss and potentially blindness.Currently,surgical,physical,and pharmacological therapies are the main clinical approaches for treating CNV.Surgical treatment aims to remove abnormal vascular tissue or perform corneal trans-plantation to inhibit angiogenesis;however,it carries a risk of postoperative rejection.Physical therapy involves the direct application of non-invasive modalities,such as laser treatment,to the neovascularized area to suppress vascular growth.Nevertheless,this approach may cause damage to surrounding healthy tissues.Pharmacotherapy has recently become a research hotspot in CNV treatment due to its convenient administration.Clinically,the drugs used for CNV treatment mainly include anti-inflammatory agents,anti-VEGF drugs,and immunosuppressants,which inhibit CNV progression by targeting angiogenesis-related signaling pathways.However,these drugs often lead to drug resistance and toxic side effects.Therefore,there is an urgent need to develop more effective and safer therapeutic agents for CNV.This article reviews the current clinical treatment status of CNV and highlights recent advances in the use of small molecule extracts from traditional Chinese medicine for CNV therapy,aiming to provide potential candidate drugs and a scientific theoretical basis for clinical management of CNV.

Patients with chronic kidney disease (CKD) have a relatively high risk of cardiovascular disease (CVD). Risk stratification guided by CVD risk prediction models is essential for managing CKD populations. We reviewed the outcome events, predictive variables, modeling methods, and predictive performance of CVD risk prediction models in CKD populations. We found a large variability in predictive outcomes, number of predictors, and sample sizes across studies. The models tended to overestimate the CVD risk of CKD populations. There are few independently validated or constructed CVD risk prediction models for CKD populations in developing countries, and in particular, there is a lack of independent external validation studies of model calibration. Future studies should comply with the reporting standards of risk prediction models to better support the application of CVD risk prediction models for CKD populations.

Objective:To systematically summarize and comparatively analyze the development, establishment and usage of oncology drugs speedy review approaches in China and in the United States between 2012 and 2021.Methods:Based on National Medical Products Administration (NMPA) and Food and Drug Administration (FDA) websites, the development and current status of the speedy review approaches were consulted and summarized. Approved oncology drugs in China and in the United States (87 in China, 118 in the United States) over the past decade were analyzed using chi-square test for group comparison.Results:Five speedy approaches have been established in China and in the United States, three of which are the same, priority review, conditional approval or accelerated approval and breakthrough therapy. The rest two are special review and approval, special examination and approval in China, and fast track and real-time oncology review in the United States. Compared to the United States, speedy review approaches in China set up late (1992 vs. 2005). The overall utilization rates of the oncology drugs speedy review approaches were similar between the China and United States (90.8% vs. 92.4%, P=0.800) in the previous 10 years, and priority review have highest utilization rates in both China and the United States without significant group difference (77.0% vs. 82.2%, P=0.381); relatively low utilization rates of conditional approval (31.0% vs. 44.9%, P=0.041) and breakthrough therapy (2.3% vs. 50.0%, P＜0.001) were seen in China. 52.9% of new drugs applied for special examination and approval in China and 40.7% of new drugs applied for fast track in the United States. Overall, the priority review both in China and the United States are stable, with a similar average annual utilization rate (84.8% vs. 83.7%); accelerated approval and breakthrough therapies in the United States fluctuate wildly, but the situation is tending towards stability in the last 3 years. Conclusions:Both China and the United States have established a relatively complete accelerated review system, with an overall utilization rate over 90%; China's accelerated review started late, although the overall utilization rate is close to that of the United States. The utilization rates of conditional approval and breakthrough therapy are still relatively low. Flexible usage of speedy review approaches, gaining regulatory recognition to use alternative endpoints, achieving real-time review and guidance are keys to accelerate new drug development in China.

Objective To explore the effects of modulating the Hippo-YAP/TAZ pathway using Huashi Runzao Prescription(HRP)on the apoptosis and salivary secretion function of submandibular gland cells in a naive non-obese diabetic(NOD/Ltj)mouse model of Sj?gren's syndrome(SS).Methods Eight-week-old female BALB/c mice were selected as the blank group.Eight-week-old female NOD/Ltj were randomly divided into the model,HRP-L,HRP-M,HRP-H,and hydroxychloroquine sulphate(HCQ)groups.After eight weeks of drug administration,the water consumption and salivary flow rate of each group were recorded.The histopathological damage of the submandibular gland in each group was determined using hematoxylin and eosin staining,the apoptosis rate of the submandibular gland was determined using TUNEL staining,and AQP5,Bax,Bcl-2,beclin-1,YAP,p-YAP,and TAZ expressions in submandibular gland tissues were determined using immunohistochemistry and Western blotting.Results Compared with the blank group,the Hippo-YAP/TAZ pathway was inhibited in the submandibular gland tissues of the model group,lymphocyte infiltration increased,water consumption increased,salivary flow rate decreased,AQP5 expression decreased,and submandibular gland cells apoptosis rate increased(P<0.05).Compared with all other administered groups,in the HRP-M group,the Hippo-YAZ/TAZ pathway was significantly activated,lymphocyte infiltration in submandibular gland tissues was reduced,water consumption was reduced,the salivary flow rate and AQP5 expression were increased,and the apoptosis rate of submandibular gland cells was reduced(P<0.05).Conclusion HRP reduced the pathological damage and apoptosis of submandibular gland cells in SS model mice.It improved the overall secretory function of submandibular gland tissues,which may be related to Hippo pathway activation and downregulating YAP/TAZ expression.