Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*

Glaucoma is a group of optic nerve disorders characterized by progressive optic nerve atrophy and visual field defects, which can lead to irreversible blindness. Early diagnosis of glaucoma is essential for preventing visual loss. However, due to the absence of obvious early symptoms, the diagnosis of glaucoma remains challenging. Visual electrophysiological examinations, an objective approach for evaluating visual function, have the potential to be used in the early diagnosis of glaucoma. This review integrates the latest publications to introduce visual electrophysiological examination techniques, including electroretinography(ERG)and visual evoked potential(VEP). It also explores the mechanisms underlying these techniques and their application value in the early diagnosis of glaucoma. In addition, this review summarizes the advantages, limitations, and applicable scenarios of different visual electrophysiological techniques. Finally, the review provides an outlook on the development prospects of visual electrophysiological techniques in the early diagnosis of glaucoma. The findings of this review can assist clinicians in selecting appropriate diagnostic methods, promote the innovation and development of early visual electrophysiological diagnostic techniques for glaucoma, and contribute to reducing the risk of blindness caused by glaucoma.

Objective To evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans ; Venous Thrombosis/therapy* ; Retrospective Studies ; Thrombolytic Therapy/methods* ; Male ; Female ; Middle Aged ; Fractures, Bone/complications* ; Lower Extremity/injuries* ; Anticoagulants/therapeutic use* ; Aged ; Treatment Outcome ; Adult

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective:To analyze the screening results of the Urban Cancer Early Diagnosis and Treatment Project in Qinghai Province from 2019 to 2024.Methods:A summary and statistical analysis were conducted on six years of screening data from the Urban Cancer Early Dia-gnosis and Treatment Program in Qinghai Province,with the high-risk rate,screening rate,and detection rate calculated separately for each type of cancer.Results:From 2019 to 2024,56,882 high-risk individuals were identified.The high-risk rates for lung,colorectal,breast,up-per gastrointestinal,and liver cancer were 22.02%,21.57%,14.23%,13.52%,and 6.10%,respectively.Overall,13,592 individuals com-pleted clinical screening,with detection rates of 0.32%for lung cancer,0.41%for liver cancer,0.08%for precancerous gastric lesions,3.63%for precancerous colorectal lesions,0.08%for esophageal cancer,0.16%for gastric cancer,and 0.14%for colorectal cancer.Conclusions:The implementation of the Urban Cancer Early Diagnosis and Treatment Program in Qinghai Province aids in the early detection of cancer,improves early diagnosis and survival rates,and reduces mortality.Nevertheless,due to low public awareness and limited participation,en-hancements in program management and public outreach are required.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Objective:To investigate the clinical efficacy of a self-designed assistant device for distal ulnar osteotomy and reduction in the surgical treatment of ulnar impaction syndrome.Methods:A retrospective analysis was performed to study the clinical data from the 27 patients with ulnar impaction syndrome who had been treated by distal ulnar shortening and fixation with 2 screws between January 2022 and August 2024 at Department of Hand and Foot Surgery,Affiliated Hospital of Jining Medical University. The cohort included 6 males and 21 females, with 13 left and 14 right sides affected and a mean age of (40.3±10.8) years (range: from 17 to 59 years). Based on their different assistant methods in osteotomy, the patients were divided into group A (15 cases) subjected to conventional freehand osteotomy and group B (12 cases) subjected to distal ulnar osteotomy and reduction assisted by our self-designed assistant device. Comparisons were made between the 2 groups regarding operative time, bone healing time, Mayo wrist function score at postoperative 16 weeks, number of the patients returning to their original occupations and complications.Results:There were no significant dif- ferences in the baseline characteristics between the 2 groups ( P>0.05). All patients were followed up postoperatively for (27.1±11.1) weeks (range: from 16 to 50 weeks). In group B, the operative time [50.0 (50.0, 62.5) min] and bone healing time [6.5 (6.0, 7.0) weeks] were significantly shorter than those in group A [80.0 (67.5, 92.5) min and 7.5 (6.8, 9.0) weeks] ( P<0.05). At postoperative 16 weeks, the Mayo wrist function score was 90.0 (85.0, 96.8) points for group A and 92.5 (85.0, 98.8) points for group B, showing no significant difference ( P>0.05). Five patients in group A and 4 ones in group B returned to their original work status, showing no significant difference either ( P>0.05). One case of non-union occurred in group A while no complication occurred in group B, demonstrating no significant difference either ( P>0.05). Conclusion:In the surgical treatment of ulnar impaction syndrome, compared with conventional freehand osteotomy, application of our self-designed assistant device for distal ulnar osteotomy and reduction is simple, less invasive, and comparable in functional recovery of the wrist, but superior in operative time and bone healing time.

Objective To investigate the correlation between the anterior ethmoidal artery(AEA)and anatomical variations of the anterior cranial base,and to analyze the predictive factors for AEA suspension.Methods Sinus CT imaging data of 159 patients undergoing endoscopic sinus sur-gery(ESS)were retrospectively analyzed.Mimics 21.0 software was utilized for three-dimensional reconstruction,measuring parameters of AEA and anterior cranial base anatomy and performing classi-fication.Pearson and Spearman correlation analyses were used to evaluate the correlations among vari-ous anatomical parameters and their classifications.Multivariate binary logistic regression analysis was performed to screen for independentpredictive factors of AEA suspension.Results The rates of AEA suspension differed significantly across different Keros classifications(P＜0.001),with an increase rate as the Keros classification level increased(P＜0.001).The transverse diameter,height and vol-ume of supraorbital ethmoid cells(SOEC),olfactory fossa depth,lateral lamella of the cribriform plate(LLCP)length and frontal sinus pneumatization classification grade were positively correlated with the distance from AEA to the cranial base(P＜0.05).Multivariate binary Logistic regression analysis showed that the presence of SOEC(OR=4.178,95％CI,2.517 to 6.935,P＜0.001),in-creased olfactory fossa depth(OR=1.433,95％CI,1.197 to 1.715,P＜0.001),and higher frontal sinus pneumatization classification grade(OR=1.621,95％CI,1.121 to 2.345,P=0.01)were independent predictive factors for AEA suspension.Conclusion Detailed preoperative CT imaging assessment,especially the analysis of SOEC,olfactory fossa depth and frontal sinus pneumatization classification,aids in accurately assessing the anatomical position of AEA,thereby effectively reduc-ing the risk of AEA injury,and improving the safety and success rate of surgery.