Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

OBJECTIVE: To explore the effectiveness and feasibility of two osteotomy guides in medial open wedge high tibial osteotomy (MOWHTO). METHODS: Clinical data of 103 patients who underwent routine MOWHTO surgery between January 2020 and December 2022 were collected for retrospective analysis. The patients were divided into two groups based on the method of osteotomy guide plate. The control group of 51 patients received traditional osteotomy guide plate technique, including 17 males and 34 females, aged from 48 to 68 years old with an average of(57.93±4.82) years old, with a disease duration ranged from 1 to 8 years with an average of (4.89±1.49) years. The observation group of 52 patients received personalized osteotomy guide plate technique, including 23 males and 29 females, aged from 48 to 69 with an average of (58.22±5.10) years, with a disease duration ranged from 1 to 9 years with an average of(5.10±1.55) years. The perioperative indicators, complications, and knee joint recovery rate were statistically analyzed for both groups, as well as the preoperative and postoperative coagulation function, fibrinogen (FIB), D-dimer (D-D), gait parameters (step frequency, step length, step speed), biomechanical indicators, weight bearing line (WBL), medial proximal tibial angle (MPTA), joint line conergence angle (JLCA), and anterior cruciate ligament (ACL) function (body width, tibial anterior displacement). RESULTS: All patients were followed up for 6 months. The intraoperative blood loss, operation time, and number of fluoroscopic views in the observation group were (358.58±93.76) ml, (84.42±8.17) min, and (2.00±0.44) times, respectively, which were all less than those in the control group (465.55±105.38) ml, (96.53±10.51) min, and (6.31±0.58) times (P<0.05). Three days after surgery, the FIB and D-D levels in the observation group were (4.21±0.48) g·L^-1 and (204.47±35.59) μg·L^-1, respectively, which were both lower than those in the control group (5.56±0.57) g·L^-1 and (311.12±42.23) μg·L^-1 (P<0.05). Three months after surgery, the step frequency, step length, and step speed in the observation group were (1.89±0.23) steps·s^-1, (0.57±0.15) m, and (0.99±0.11) m·s^-1, respectively, which were all higher than those in the control group (1.80±0.18) steps·s^-1, (0.50±0.14) m, and (0.95±0.09) m·s^-1 (P<0.05). Three months after surgery, the WBL and MPTA in the observation group were (45.53±4.41)% and (87.03±8.15)°, respectively, which were both higher than those in the control group (38.38±4.36)% and (83.68±8.50)°, and the JLCA was (2.36±0.24)°, which was lower than that in the control group (2.61±0.33)° (P<0.05). The ACL body width during internal fixation removal was (5.60±0.51) mm, which was greater than that in the control group (5.08±0.56) mm, and the tibial migration was (5.70±0.42) mm, which was less than that in the control group (6.33±0.48) mm (P<0.05). There was no significant difference in the incidence of complications between the two groups (P>0.05). Six months after surgery, there was no significant difference in the recovery rate of knee joint between the two groups (P>0.05). CONCLUSION The application of personalized osteotomy guide technique in MOWHTO can help improve knee biomechanics and ACL function, and has less effect on coagulation function and no increase in complications.
Humans ; Male ; Female ; Osteotomy/methods* ; Middle Aged ; Tibia/physiopathology* ; Aged ; Biomechanical Phenomena ; Retrospective Studies ; Osteoarthritis, Knee/physiopathology*

Objective To analyze the risk factors of gastrointestinal bleeding in patients with type A aortic dissection(TAAD)after Sun's operation.Methods The clinical data of 87 patients who underwent TAAD Sun's operation in our hospital from March 2021 to June 2022 were retrospectively analyzed.They were divided into the bleeding group and the non-bleeding group according to whether there was gastrointestinal bleeding after operation.The clinical data of patients in the two groups was compared and analyzed.The binary Logistic regression analysis was used to analyze the risk factors of gastrointestinal bleeding.The clinical predictor of postoperative gastrointestinal bleeding was analyzed by receiver operating characteristic(ROC)curve.Results In this study,there were 40 cases of postoperative gastrointestinal bleeding(the bleeding group)and 47 cases of non-bleeding(the non-bleeding group).Compared with the non-bleeding group,the bleeding group had a shorter onset time,a higher proportion of patients with hypertension history,a higher preoperative creatinine abnormality rate,more intraoperative blood loss,longer postoperative mechanical ventilation time,higher postoperative infection rate,and higher poor prognosis rate,with statistically significant differences(P<0.05).There was no statistically significant difference in the gender,age,gastrointestinal diseases history,smoking history,preoperative platelets,preoperative international normalized ratio(INR),preoperative alanine aminotransferase(ALT),preoperative aspartate aminotransferase(AST),preoperative γ-glutamyl transpeptidase(GGT),preoperative dissection involving abdominal aorta,operation time,intraoperative cardiopulmonary bypass time,intraoperative circulatory arrest time,intraoperative aortic occlusion time or intraoperative blood transfusion rate.Logistic regression analysis showed that hypertension history(OR=2.468,95%CI:0.862 to 7.067,P=0.037),preoperative creatinine>105 μmol/L(OR=3.970,95%CI:1.352 to 11.659,P=0.011),long postoperative mechanical ventilation time(OR=1.015,95%CI:0.094 to 1.018,P=0.041)and postoperative infection(OR=3.435,95%CI:0.991 to 11.900,P=0.012)were the independent risk factors for postoperative gastrointestinal bleeding in TAAD patients.ROC curve showed that the postoperative mechanical ventilation time exceeding 64 hours were the clinical predictor of postoperative gastrointestinal bleeding in TAAD patients.Conclusion The prognosis of TAAD patients with postoperative gastrointestinal bleeding after Sun's operation is poor.Hypertension history,preoperative acute renal insufficiency,long postoperative mechanical ventilation time and postoperative infection are closely related to postoperative gastrointestinal bleeding in TAAD patients after operation,which should be paid more attention to,and corresponding evaluation,early identification and early intervention should be made to improve the prognosis of patients.

Aim To design the pyrimidoindole deriva-tive N-butyl-9H-pyrimido[4,5-b]indole-2-carboxamide(BFPI)and synthesize it to investigate whether it in-hibits macrophage pyroptosis and foaming effects through the NLRP3/Caspase-1 pathway.Methods BFPI was synthesized using 2,4,6-triethoxycarbonyl-l,3,5-triazine and 2-aminoindole as starting materials and structurally characterized by 1H NMR,13C NMR,and ESI-MS.The in vitro cultured mouse monocyte macro-phage cell line RAW264.7 was divided into blank,model(PA)and therapeutic(BFPI)groups,and the cells in each group were treated with the corresponding culture medium for 24 h.The proliferative viability was detected by MTT assay,and the formation of intracel-lular lipid droplets was detected by oil red O staining,and NLRP3 was detected by Western-blot and RT-qPCR,caspase-1 and MCP-1 mRNA and protein ex-pression levels by Western blot and RT-qPCR.Results Compared with the blank group,the proliferation vi-ability of cells in the model group significantly de-creased and the formation of lipid droplets significantly increased;compared with the model group,the prolif-eration viability of cells in the treatment group signifi-cantly increased and the formation of lipid droplets sig-nificantly decreased,and the differences were statisti-cally significant(P＜0.01);compared with the blank group,the cellular NLRP3,caspase-1 and MCP-1 mR-NA and protein expression levels of cells in the model group significantly increased;compared with the model group,the expression levels of the above indexes of the cells in the treatment group significantly decreased,and the difference was statistically significant(P＜0.01).Conclusions BFPI contributes to delaying macrophage-derived foam cell formation during athero-genesis by inhibiting macrophage NLRP3,caspase-1,and MCP-1 expression and thereby promoting their pro-liferation and inhibiting lipid phagocytosis.

Objective To evaluate the management and indicators of pathogen detection before antimicrobial treat-ment for inpatients in second level and above medical institutions(MIs)in Guangdong Province,and provide direc-tion and decision-making basis for the improvement of pathogen detection quality in the region.Methods The ma-nagement status,information system functions,and pathogen detection rate indicators of secondary and above MIs in 21 cities in Guangdong Province was surveyed through online questionnaire surveys and system submission.A baseline survey on sentinel monitoring MIs was conducted from July 15th to August 8th,2023.From November 7th to 30th,a baseline survey on non-sentinel monitoring MIs was launched.Surveys on indicator information of all MIs were completed from January 15th to 30th,2024.Results A total of 265 MIs were surveyed,and the proportions of establishing special working groups(83.98％),developing special action improvement plans(79.01％),estab-lishing pathogen detection rate management systems(91.71％),and developing management assessment plans(76.80％)of tertiary MIs were all higher than that of secondary MIs,differences were all statistically significant(all P＜0.05).The proportion of tertiary MIs with various information system functions was higher than that of secondary MIs(all P＜0.05).The pathogen detection rate(61.07％)before antimicrobial treatment and health-care-associated infection(HAI)diagnosis-related pathogen detection rate(88.00％)of inpatients in tertiary MIs were both higher than those in secondary MIs(both P＜0.05).Among different types of MIs,pathogen detection rate before antimicrobial treatment of inpatients in maternal and child health MIs was higher than that in other types of MIs.HAI diagnosis-related pathogen detection rate in other specialized hospitals was the highest,and pathogen detection rate before combined use of key antimicrobial treatment in traditional Chinese medicine hospitals was the lowest,differences were all statistically significant(all P＜0.05).Conclusion Tertiary MIs have more advantages in management strategies and information technology construction than secondary MIs,secondary MIs need more guidance and support.Monitoring and analysis of pathogen detection rate indicators in MIs of different levels and types should be strengthened through special actions.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Objective To evaluate the management and indicators of pathogen detection before antimicrobial treat-ment for inpatients in second level and above medical institutions(MIs)in Guangdong Province,and provide direc-tion and decision-making basis for the improvement of pathogen detection quality in the region.Methods The ma-nagement status,information system functions,and pathogen detection rate indicators of secondary and above MIs in 21 cities in Guangdong Province was surveyed through online questionnaire surveys and system submission.A baseline survey on sentinel monitoring MIs was conducted from July 15th to August 8th,2023.From November 7th to 30th,a baseline survey on non-sentinel monitoring MIs was launched.Surveys on indicator information of all MIs were completed from January 15th to 30th,2024.Results A total of 265 MIs were surveyed,and the proportions of establishing special working groups(83.98％),developing special action improvement plans(79.01％),estab-lishing pathogen detection rate management systems(91.71％),and developing management assessment plans(76.80％)of tertiary MIs were all higher than that of secondary MIs,differences were all statistically significant(all P＜0.05).The proportion of tertiary MIs with various information system functions was higher than that of secondary MIs(all P＜0.05).The pathogen detection rate(61.07％)before antimicrobial treatment and health-care-associated infection(HAI)diagnosis-related pathogen detection rate(88.00％)of inpatients in tertiary MIs were both higher than those in secondary MIs(both P＜0.05).Among different types of MIs,pathogen detection rate before antimicrobial treatment of inpatients in maternal and child health MIs was higher than that in other types of MIs.HAI diagnosis-related pathogen detection rate in other specialized hospitals was the highest,and pathogen detection rate before combined use of key antimicrobial treatment in traditional Chinese medicine hospitals was the lowest,differences were all statistically significant(all P＜0.05).Conclusion Tertiary MIs have more advantages in management strategies and information technology construction than secondary MIs,secondary MIs need more guidance and support.Monitoring and analysis of pathogen detection rate indicators in MIs of different levels and types should be strengthened through special actions.

OBJECTIVE: To investigate the effectiveness of percutaneous pedicle screw fixation combined expandable tubular retractor in the treatment of patients with spinal metastases. METHODS: In the study, 12 patients of spinal metastases treated with percutaneous pedicle screw fixation combined expandable tubular retractor in our hospital were retrospectively reviewed between June 2017 and October 2019. Among the 12 patients, 9 were males and 3 were females; the median age was 62.5 years [(65.1±2.9) years]. The decompression segment of 7 patients was located at the lower thoracic spine (including 1 patient with incomplete paraplegia) and the decompression segment of 5 patients was located at the lumbar spine; Tomita score was 6.0±0.6. Perioperative data of the patients were reviewed. Visual analog scale (VAS score), Karnofsky score, and Eastern Cooperative Oncology Group (ECOG) score were compared before and after surgery. The patient's survival, adjuvant treatment, and internal fixation failure were observed in the follow-up period. RESULTS: All the 12 patients had a successful operation with percuta-neous pedicle screw fixation combined expandable tubular retractor. The average operative time, blood loss, and blood transfused of the patients were (247.0±14.6) min, (804.2±222.3) mL and (500.0±100.0) mL, respectively. The average amount of drainage was (240.8±79.3) mL. Drainage tubes were pulled out early postoperative [(3.2±0.3) d], allowing early mobilization. The patients discharged (7.8±0.8) d postoperative. All the patients were followed up for 6-30 months, and the average overall survival time was (13.6±2.4) months. During the follow-up period, 2 patients experienced screw displacement, the internal fixation was stable after conservative treatment and no revision surgery was performed. The VAS of the patients was 7.1±0.2 before surgery, which decreased to 2.3±0.1 and 2.8±0.4 at 3 and 6 months after surgery (P < 0.05). The Karnofsky score of the patients was 59.2±1.9 before surgery, which increased to 75.0±1.9 and 74.2±3.1 at 3 and 6 months after surgery (P < 0.05). The ECOG of the patients was 2.3±0.2 before surgery, which decreased to 1.7±0.1 and 1.7±0.2 at 3 and 6 months after surgery (P < 0.05). CONCLUSION For selected patients with spinal metastases, minimally invasive surgical treatment of spinal metastases (percutaneous pedicle screw internal fixation combined with expandable tubular retractor) can effectively relieve the clinical symptoms and improve the quality of life, with satisfactory clinical outcome.
Male ; Female ; Humans ; Middle Aged ; Pedicle Screws ; Treatment Outcome ; Spinal Neoplasms/surgery* ; Quality of Life ; Retrospective Studies ; Fracture Fixation, Internal ; Lumbar Vertebrae/surgery* ; Thoracic Vertebrae/surgery* ; Spinal Fusion ; Spinal Fractures/surgery*

Objective: To examine the clinical value of fluorescence-guided indocyanine green (ICG) laparoscopic anatomical hepatectomy in the treatment of primary hepatocellular carcinoma. Methods: Data from patients diagnosed with hepatocellular carcinoma and who underwent laparoscopic hepatectomy with ICG fluorescence navigation in the Department of Liver Surgery and Liver Transplantation Center of West China Hospital between September 2020 and May 2022 were retrospectively collected. There were 53 males and 19 females, with an age of (55.5±12.9)years(range:42.6 to 68.4 years). Among them, 13 of the cases underwent laparoscopic anatomical liver resection(LALR) guided by tans-arterial ICG,43 of the cases received LAIR guided by portal vein negative ICG, and 16 of the cases received LALR positive by portal vein. Comparison among the three groups was performed by one-way ANOVA; and the rank sum test was used for comparison between groups. The counting data was expressed as percentage,and the χ² test or Fisher's exact probability method was used for comparison between groups. Results: (1) Postoperative pathology: Resection R0 was achieved in all operations. The maximum tumor diameter of the patients in the arterial staining group, the reverse staining group, and the positive staining group(M (IQR)) was 2.5 (2.4) cm, 3.0 (2.5) cm and 3.0(2.4) cm,respectively. There were no statistically significant differences in the maximum tumor diameter between the three groups (P=0.364). The minimum tumor margin was 1.1 (1.1) cm, 1.0 (1.0) cm, 1.1 (1.6) cm in the the arterial staining group, reverse staining group and the positive staining group, respectively. There was no significant difference in the margin among the three groups (P=0.878). (2) Operation conditions: the operation time of the arterial staining group, the negative staining group, and the positive portal staining group was (348±93)minutes,(277±112)minutes,and (295±116)minutes,respectively. There were no significant differences in operation time among the three groups (P=0.134). The intraoperative blood loss of the three groups was 80(150)ml,200(350)ml,and 100(150)ml,respectively. There was no statistically significant difference in intraoperative bleeding volume between the three groups(P=0.743). All cases were not transfused during the operation and were not converted to laparotomy. ALT in the arterial staining group was higher than in the negative staining group in the first two days after the operation ((559±398)IU/L307(257) IU/L, q=235.5,P=0.004;(611±389)IU/L(331±242) IU/L, q=265.2, P=0.002). There was only one case of a grade III complication (Clavien-Dindo grading system) postoperative complication in the negative and positive staining group of the portal vein, respectively. Tumor markers in all patients decreased to the normal range after 2 months of operation. Conclusion: Laparoscopic anatomical hepatectomy guided by ICG fluorescence through arterial staining and portal vein staining is safe and feasible for primary hepatocellular carcinoma treatment.