Necroptosis is a regulated process of programmed cell death independent of aspartic acid-specific cysteine protease,which can induce inflammation.Studies have shown that necroptosis is closely related to the progression and prognosis of pancreatic disease and plays an important two-way regulatory role in its progression.Related necroptosis inhibitors and inducers are expected to be used in the treatment of pancreatic disease.We herein review the mechanism of necroptosis and its role in the progression of pancreatic disease to provide a new understanding of the pathogenesis and treatment of pancreatic diseases and offer a theoretical basis for the research and development of targeted drugs.

ObjectiveThis study aims to examine the effect of Rhei Radix et Rhizoma-Coptidis Rhizoma on reducing insulin resistance in db/db mice by regulating the adenylate activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1）/key molecule of autophagy， benzyl chloride 1 （Beclin1） pathway and elucidate the underlying mechanism. MethodSixty 6-week-old male db/db mice were studied. They were randomly divided into the model group， metformin group （0.26 g·kg^-1）， and low-， middle-， and high-dose groups （2.25， 4.5， 9 g·kg^-1） of Rhei Radix et Rhizoma-Coptidis Rhizoma. A blank group of db/m mice of the same age was set， with 12 mice in each group. After eight weeks of continuous intragastric administration， the blank group and model group received distilled water intragastrically once a day. The survival status of the mice was observed， and fasting blood glucose （FBG） was measured using a Roche blood glucose device. Fasting serum insulin （FINS） was measured using an enzyme-linked immunosorbent assay， and the insulin resistance index （HOMA-IR） was calculated. Hematoxylin-eosin （HE） staining was performed to observe the pathological changes in the liver of the mice. The protein expression levels of AMPK， Beclin1， autophagy associated protein 5 （Atg5）， and p62 in liver tissue were determined by using Western blot. The protein expression levels of autophagy associated protein 1 light chain 3B （LC3B） and ULK1 in liver tissue were determined using immunofluorescence. Real-time fluorescence quantitative PCR （Real-time PCR） was used to measure mRNA expression levels of AMPK， Beclin1， Atg5， ULK1， and p62. ResultCompared with the blank group， the model group exhibited a significant increase in body mass （P<0.01）. Additionally， the levels of FBG， FINS， and HOMA-IR significantly changed （P<0.01）. The structure of liver cells was disordered. The protein expression levels of AMPK， Beclin1， and Atg5 in liver tissue were significantly decreased （P<0.01）， while the expression level of p62 protein was significantly increased （P<0.01）. The expression levels of mRNA and proteins were consistent. Compared with the model group， the body mass of the metformin group and high and medium-dose groups of Rhei Radix et Rhizoma-Coptidis Rhizoma was significantly decreased （P<0.05）. FBG， FINS， and HOMA-IR were significantly decreased （P<0.05，P<0.01）. After treatment， the liver structure damage in each group was alleviated to varying degrees. The protein expressions of AMPK， Beclin1， Atg5， LC3B， and ULK1 were increased （P<0.05，P<0.01）， while the protein expression of p62 was decreased （P<0.01）. The expression levels of mRNA and proteins were generally consistent. ConclusionThe combination of Rhei Radix et Rhizoma-Coptidis Rhizoma can effectively improve liver insulin resistance， regulate the AMPK autophagy signaling pathway， alleviate insulin resistance in db/db mice， and effectively prevent the occurrence and development of type 2 diabetes.

Objective To research the procedure for creating an animal model of mitral regurgitation by implanting a device through the apical artificial chordae tendineae, and to assess the stability and dependability of the device. Methods Twelve large white swines were employed in the experiments. Through a tiny hole in the apex of the heart, the artificial chordae tendineae of the mitral valve was inserted under the guidance of transcardiac ultrasonography. Before, immediately after, and one and three months after surgery, cardiac ultrasonography signs were noted. Results All models were successfully established. During the operation and the follow-up, no swines died. Immediately after surgery, the mitral valve experienced moderate regurgitation. Compared with preoperation, there was a variable increase in the amount of regurgitation and the values of heart diameters at a 3-month follow-up (P<0.05). Conclusion In off-pump, the technique of pulling the mitral valve leaflets with chordae tendineae implanted transapically under ultrasound guidance can stably and consistently create an animal model of mitral regurgitation.

To investigate the clinical assessment of dual-enhanced antiplatelet therapy after cerebrovascular intervention to reduce the risk of cerebral infarction recurrence, and to provide a reference for the prevention and treatment of cerebral infarction recurrence risk. 202 patients with cerebral infarction who underwent cerebrovascular intervention in Tianjin Fifth Central Hospital from January 2018 to October 2022 were selected as study subjects. The patients were divided into a treatment group ( n=104) based on randomized controlled single-blind method with 61 males and 43 females with a mean age of (62.33±2.57) years old and a control group ( n=98) with 56 males and 42 females with a mean age of (62.49±2.36) years old. The control group was given aspirin mono-antiplatelet therapy, and the treatment group was given clopidogrel doublet augmented antiplatelet therapy on the basis of the control group, and both groups continued the treatment for 2 months. Platelet counts, coagulation indexes and inflammatory factors were compared between the two groups before and after treatment, and the America National Institutes of Health Stroke Scale (NIHSS) score was used to assess the neurological functions of the two groups before and after treatment, and the recurrence of cerebral infarction in the two groups was counted within 6 months after treatment. In addition, the patients in the treatment group were divided into the cerebral infarction recurrence group and the cerebral infarction non-recurrence group according to whether they had cerebral infarction recurrence within 6 months after treatment, and the clinical data of the patients in the treatment group were collected to analyze the influencing factors of the dual-enhancement antiplatelet therapy for the recurrence of cerebral infarction in patients with cerebral infarction after cerebral vascular intervention by multifactorial logistic regression. The results showed that after treatment, patients in the treatment group had an international normalized ratio (INR) of (1.76±0.38), a platelet activation rate of (39.52±4.79)%, a platelet aggregation rate of (48.54±5.21)%, a tumor necrosis factor-alpha (TNF-alpha) of (28.37±4.47)ng/L, an interleukin 6 (IL-6) of (24.77±3.52)ng/L, a high-sensitivity C-reactive protein (hs-CRP) of (7.39±1.53)mg/L and an NIHSS score of (6.11±1.39) were lower than those of the control group (2.32±0.41), (44.81±6.37)%, (51.39±5.58)%, (39.66±4.51) ng/L, (29.25±4.04) ng/L, (9.03±1.78) mg/L and (9.93±1.46) points (all P<0.05). At 6-month follow-up of all patients, cerebral infarction recurred in 16 (15.38%) patients in the treatment group and in 33 (33.67%) patients in the control group ( χ2=9.185, P<0.05). Kaplan-Meier results showed a statistically significant difference in the rate of recurrence without cerebral infarction in the treatment group compared with the control group(LogRank χ2=4.595, P<0.05). Logistic regression analysis showed that smoking history, cervical vascular plaque, post-treatment NIHSS score, post-treatment stenosis score, post-treatment INR, post-treatment hs-CRP and CYP2C19 gene polymorphism were independent influences on the recurrence of cerebral infarction in cerebral infarction patients with cerebral vascular interventions followed by doublet augmentation of antiplatelet therapy (all P<0.05). In conclusion, dual-enhanced antiplatelet therapy may be an effective measure to reduce the risk of cerebral infarction recurrence after cerebrovascular intervention in patients with cerebral infarction, but it is still influenced by more factors.

Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

Objective:To investigate the protective effect of quercetin against LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, providing valuable insights into the use of quercetin as a virulence inhibitor for Pseudomonas aeruginosa infection treatment. Methods:This was an experimental study. The experimental strain was the standard strain. The LasB protein was obtained utilizing protein recombination technology, while the enzyme activity of LasB was assessed through both the Elastin Congo red assay and fluorescently labelled elastin assay. The LasB-induced THP-1 macrophage infection model was established, and quercetin was utilized for intervention. Cell viability was evaluated via CCK-8 assay, while cell morphology was observed under an inverted microscope. Apoptosis detection involved employing both TUNEL and Annexin V/PI staining. The mRNA expression and protein levels of inflammatory cytokines and COX-2 were determined by RT-qPCR and ELISA respectively. Intracellular ROS levels were quantified using the DCFH-DA fluorescent probe. One-way ANOVA was used for statistical analysis, and Tukey test was used for multiple comparisons. Results:The pLasB with a molecular weight of 33 000 and acceptable enzymatic activity (purity>90%), was successfully obtained. THP-1 macrophages treated with pLasB at a concentration of 100 μg/ml presented significantly decreased viability and integrity rate when compared with the normal control group. Additionally, pLasB promoted apoptosis, up-regulated the levels of inflammatory cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12, and TNF-α, increased intracellular ROS fluorescence intensity, and elevated COX-2 mRNA expression level. Furthermore, the viability of THP-1 macrophages was significantly enhanced under quercetin intervention at concentrations of 2.5 μmol/L, 5 μmol/L and 10 μmol/L. The apoptosis rate exhibited a significant reduction from 18.32%±0.17% to 13.17%±0.20%, 11.43%±0.06% and 7.74%±0.04%, respectively ( F=1 679, P<0.05). There was a notable down-regulation of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-12 and TNF-α while the anti-inflammatory cytokine IL-10 showed a significant up-regulation. Both intracellular ROS fluorescence intensity ( F=86.92, P<0.05) and COX-2 level ( F=24.62, P<0.05) demonstrated a substantial decrease. Conclusion:Quercetin demonstrates significant efficacy in inhibiting LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, which highlights immense potential as a potent virulence inhibitor of Pseudomonas aeruginosa.

To investigate the clinical assessment of dual-enhanced antiplatelet therapy after cerebrovascular intervention to reduce the risk of cerebral infarction recurrence, and to provide a reference for the prevention and treatment of cerebral infarction recurrence risk. 202 patients with cerebral infarction who underwent cerebrovascular intervention in Tianjin Fifth Central Hospital from January 2018 to October 2022 were selected as study subjects. The patients were divided into a treatment group ( n=104) based on randomized controlled single-blind method with 61 males and 43 females with a mean age of (62.33±2.57) years old and a control group ( n=98) with 56 males and 42 females with a mean age of (62.49±2.36) years old. The control group was given aspirin mono-antiplatelet therapy, and the treatment group was given clopidogrel doublet augmented antiplatelet therapy on the basis of the control group, and both groups continued the treatment for 2 months. Platelet counts, coagulation indexes and inflammatory factors were compared between the two groups before and after treatment, and the America National Institutes of Health Stroke Scale (NIHSS) score was used to assess the neurological functions of the two groups before and after treatment, and the recurrence of cerebral infarction in the two groups was counted within 6 months after treatment. In addition, the patients in the treatment group were divided into the cerebral infarction recurrence group and the cerebral infarction non-recurrence group according to whether they had cerebral infarction recurrence within 6 months after treatment, and the clinical data of the patients in the treatment group were collected to analyze the influencing factors of the dual-enhancement antiplatelet therapy for the recurrence of cerebral infarction in patients with cerebral infarction after cerebral vascular intervention by multifactorial logistic regression. The results showed that after treatment, patients in the treatment group had an international normalized ratio (INR) of (1.76±0.38), a platelet activation rate of (39.52±4.79)%, a platelet aggregation rate of (48.54±5.21)%, a tumor necrosis factor-alpha (TNF-alpha) of (28.37±4.47)ng/L, an interleukin 6 (IL-6) of (24.77±3.52)ng/L, a high-sensitivity C-reactive protein (hs-CRP) of (7.39±1.53)mg/L and an NIHSS score of (6.11±1.39) were lower than those of the control group (2.32±0.41), (44.81±6.37)%, (51.39±5.58)%, (39.66±4.51) ng/L, (29.25±4.04) ng/L, (9.03±1.78) mg/L and (9.93±1.46) points (all P<0.05). At 6-month follow-up of all patients, cerebral infarction recurred in 16 (15.38%) patients in the treatment group and in 33 (33.67%) patients in the control group ( χ2=9.185, P<0.05). Kaplan-Meier results showed a statistically significant difference in the rate of recurrence without cerebral infarction in the treatment group compared with the control group(LogRank χ2=4.595, P<0.05). Logistic regression analysis showed that smoking history, cervical vascular plaque, post-treatment NIHSS score, post-treatment stenosis score, post-treatment INR, post-treatment hs-CRP and CYP2C19 gene polymorphism were independent influences on the recurrence of cerebral infarction in cerebral infarction patients with cerebral vascular interventions followed by doublet augmentation of antiplatelet therapy (all P<0.05). In conclusion, dual-enhanced antiplatelet therapy may be an effective measure to reduce the risk of cerebral infarction recurrence after cerebrovascular intervention in patients with cerebral infarction, but it is still influenced by more factors.

Objective:To investigate the protective effect of quercetin against LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, providing valuable insights into the use of quercetin as a virulence inhibitor for Pseudomonas aeruginosa infection treatment. Methods:This was an experimental study. The experimental strain was the standard strain. The LasB protein was obtained utilizing protein recombination technology, while the enzyme activity of LasB was assessed through both the Elastin Congo red assay and fluorescently labelled elastin assay. The LasB-induced THP-1 macrophage infection model was established, and quercetin was utilized for intervention. Cell viability was evaluated via CCK-8 assay, while cell morphology was observed under an inverted microscope. Apoptosis detection involved employing both TUNEL and Annexin V/PI staining. The mRNA expression and protein levels of inflammatory cytokines and COX-2 were determined by RT-qPCR and ELISA respectively. Intracellular ROS levels were quantified using the DCFH-DA fluorescent probe. One-way ANOVA was used for statistical analysis, and Tukey test was used for multiple comparisons. Results:The pLasB with a molecular weight of 33 000 and acceptable enzymatic activity (purity>90%), was successfully obtained. THP-1 macrophages treated with pLasB at a concentration of 100 μg/ml presented significantly decreased viability and integrity rate when compared with the normal control group. Additionally, pLasB promoted apoptosis, up-regulated the levels of inflammatory cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12, and TNF-α, increased intracellular ROS fluorescence intensity, and elevated COX-2 mRNA expression level. Furthermore, the viability of THP-1 macrophages was significantly enhanced under quercetin intervention at concentrations of 2.5 μmol/L, 5 μmol/L and 10 μmol/L. The apoptosis rate exhibited a significant reduction from 18.32%±0.17% to 13.17%±0.20%, 11.43%±0.06% and 7.74%±0.04%, respectively ( F=1 679, P<0.05). There was a notable down-regulation of pro-inflammatory cytokines IL-1α, IL-1β, IL-6, IL-12 and TNF-α while the anti-inflammatory cytokine IL-10 showed a significant up-regulation. Both intracellular ROS fluorescence intensity ( F=86.92, P<0.05) and COX-2 level ( F=24.62, P<0.05) demonstrated a substantial decrease. Conclusion:Quercetin demonstrates significant efficacy in inhibiting LasB-induced apoptosis, inflammation, and oxidative stress in THP-1 macrophages, which highlights immense potential as a potent virulence inhibitor of Pseudomonas aeruginosa.

Objective Neuromuscular electrical stimulation(NMES)-evoked kinesthetic information in muscle spindle can be purely extracted from the mixed motor and sensory afferents using Ischemic nerve block(INB).This study aims to investigate the somatosensory cortical response evoked by NMES activating muscle spindle afferents in forearm.Methods All subjects performed four experimental tasks designed according to a 2×2 factors,including one factor of the INB state(without INB and within INB)and the other of the stimulation intensity(above and below motor threshold).During the experiment,we recorded EEG data with 64 channels and then beta event-related desynchronization(Beta ERD)were utilized quantize somatosensory cortical excitability evoked by the tasks.The subjective perception about the sensation and movement of the right hand were evaluated by a psychophysical test after the right wrist was performed by INB.Results INB significantly reduced beta ERD on the contralateral somatosensory cortex evoked by NMES above the motor threshold,and there was significant difference of NMES-evoked beta ERD values on the contralateral somatosensory cortex between above and below motor threshold.Meanwhile,contralateral dominance of NMES-evoked beta ERD on the somatosensory cortex was transferred to ipsilateral hemisphere under INB.Conclusion INB can significantly reduce NMES-evoked somatosensory cortical response above motor threshold and decrease cortical perception on the stimulus intensity,which may be due to INB resulting in rapid functional reorganization of somatosensory cortex.

The diagnosis and treatment resources for rare diseases in China are highly imbalanced. The basic diagnosis and treatment capabilities are weak, the diagnosis period for patients is long, and the rates of missed diagnosis and misdiagnosis are relatively high. The establishment of a hierarchical diagnosis and treatment system is the inevitable approach to enhancing the diagnosis and treatment standards of rare diseases. Currently, the implementation of the domestic hierarchical diagnosis and treatment system for rare diseases still confronts numerous challenges, such as ambiguous referral standards and processes of primary medical institutions, and ineffective information interaction among institutions at all levels. Thus, it is essential to facilitate high-level information construction for the hierarchical diagnosis and treatment of rare diseases. This paper explores the process of constructing a multidisciplinary joint remote diagnosis and treatment platform and a health management platform through informatization, with the hope of establishing two closed loops of digital diagnosis and treatment services and health follow-up management for patients with rare diseases, as well as achieving timely diagnosis and lifelong health management for patients. It integrates and optimizes auxiliary diagnostic tools, promotes the rapid dissemination of rare disease diagnosis and treatment experiences to the grassroots, enhances the information construction level of the hierarchical diagnosis and treatment system, and endeavors to address the practical predicament of weak diagnosis and treatment capabilities of rare diseases in grassroots medical institutions. Additionally, this paper proposes an essential approach for multi-dimensional independent innovation to guide the popularization of efficient and high-quality rare disease diagnosis and treatment services. By encompassing innovating the rare disease diagnosis and treatment collaboration network and multidisciplinary diagnosis and treatment model, facilitating the application of the latest biomedical and informatics technologies to the grassroots, and constructing a national intelligent data platform for rare disease innovation, a new model for rare disease services with Chinese characteristics will be established. This will significantly enhance the medical treatment level of rare diseases in China and strive for more benefits for patients.