ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.

Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.

OBJECTIVE: To compare the effectiveness of clavicular hook plate fixation in the treatment of acromioclavicular joint dislocation and distal clavicle fractures. METHODS: A clinical data of 90 patients, who underwent clavicular hook plate fixation between January 2014 and June 2023, was retrospectively analyzed. There were 40 patients with distal clavicle fractures (fracture group) and 50 with acromioclavicular joint dislocations (dislocation group). There was no significant difference in the baseline data of gender, age, cause of injury, side of injury, time from injury to operation, and constituent ratio of osteoporosis patients between the two groups ( P>0.05). The time to remove the internal fixators and the occurrence of complications were recorded. Before removing the internal fixator and at 3 months after removing, the visual analogue scale (VAS) score was used to evaluate the degree of pain, and the mobility of the shoulder joint in forward flexion, elevation, and abduction was measured. Before removing the internal fixators, the Constant-Murley score and the University of California, Los Angeles (UCLA) score were used to evaluate the function of the shoulder joint. X-ray films of the shoulder joint were taken during follow-up to observe the occurrence of subacromial osteolysis, acromioclavicular joint osteoarthritis, and distal clavicle bone atrophy. Subgroup comparison was conducted between patients with and without subacromial osteolysis in the two groups. RESULTS: All incisions healed by first intention in both groups. All patients were followed up 1-9 years, with a median of 5 years; the difference in follow-up time between the two groups was not significant ( P>0.05). During follow-up, subacromial osteolysis occurred in 74 cases, including 41 cases of typeⅠand 33 cases of type Ⅱ, distal clavicle bone atrophy in 15 cases, and acromioclavicular joint osteoarthritis in 8 cases. There were significant differences in the removal time of internal fixators, the incidence of bone atrophy, and the incidence of osteoarthritis between the two groups ( P<0.05). There was no significant difference in the incidence of subacromial osteolysis ( P>0.05). Before removing the internal fixators, there was no significant difference in VAS score, UCLA score, and Constant-Murley score between the two groups ( P>0.05), while there were significant differences in shoulder joint range of motion in all directions ( P<0.05). After removing the internal fixators, only the difference in elevation was significant ( P<0.05). Within the group comparison, the VAS score and mobility of shoulder joint in abduction and elevation after removing the internal fixators were significantly superior to those before removing ( P<0.05). In the fracture and dislocation groups, there was only a significant difference in plate length between the subgroup with and without subacromial osteolysis ( P<0.05), while there was no significant difference in the above other indicators ( P>0.05). CONCLUSION Clavicular hook plate is a good choice for treating acromioclavicular dislocation or distal clavicle fractures, but the incidence of subacromial osteolysis is higher, and the degree of bone resorption is more severe in fracture patients. After removal of the internal fixator, the shoulder functions significantly improve. It is recommended to remove the internal fixator as soon as possible within the allowable range of the condition.
Humans ; Clavicle/surgery* ; Acromioclavicular Joint/surgery* ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Fractures, Bone/surgery* ; Male ; Retrospective Studies ; Female ; Adult ; Middle Aged ; Treatment Outcome ; Joint Dislocations/surgery* ; Aged ; Range of Motion, Articular ; Young Adult ; Postoperative Complications

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

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

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Objective:Utilizing a seven-year panel data set of a targeted admission medical student cohort,this study aims to examine their career development and provide insights for retaining healthcare talent in township health centers and village clinics in the central and western rural areas of China.Method:Starting from 2015,cohorts of targeted and general clinical graduates from four medical colleges in central and western China were selected and tracked for their career progression.Results:The targeted graduates'standardized residency training and medical licensing examination pass rates were similar to those of general clinical graduates.They advanced more quickly in professional titles and positions,with 82.5%becoming attending physicians and 16.2%obtaining positions in the seventh year after graduation.However,their monthly income was significantly lower than that of general clinical graduates,and this income discrepancy expanded annually.As of December 2022,among the 493 targeted graduates who completed their contracts,38.5%stayed in grassroots positions.Of those who left,60%moved to county-level or higher public hospitals,7.9%pursued further studies,and 27.7%were unemployed.Conclusion:Targeted graduates are well-trained and advance rapidly in their careers,but their lower income significantly impacts their willingness to remain at the grassroots level.After completing their service period,about one-third of the targeted graduates choose to stay in grassroots positions.

Objective:To analyze the changes rule of serum procalcitonin (PCT) levels in patients with traumatic brain injury in plateau areas, and to evaluate its value in assessing the severity and prognosis of the patients.Methods:A prospective cohort study was conducted. The patients with traumatic brain injury admitted to the critical care medicine departments of Xining Third People's Hospital (at an altitude of 2 260 metres) and Golmud City People's Hospital (at an altitude of 2 780 metres) from May 2018 to September 2022 were enrolled. According to the Glasgow coma scale (GCS) score at admission, the patients were divided into mild injury group (GCS score 13-15), severe injury group (GCS score 9-12), and critical injury group (GCS score 3-8). All patients received active treatment. Chemiluminescence immunoassay was used to measure the serum PCT levels of patients on the 1st, 3rd, 5th, and 7th day of admission. The Kendall tau-b correlation method was used to analyze the correlation between serum PCT levels at different time points and the severity of the disease. The patients were followed up until October 30, 2022. The prognosis of the patients was collected. The baseline data of patients with different prognosis were compared. The Cox regression method was used to analyze the relationship between baseline data, serum PCT levels at different time points and prognosis. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of serum PCT levels at different time points for death during follow-up.Results:Finally, a total of 120 patients with traumatic brain injury were enrolled, including 52 cases in the mild injury group, 40 cases in the severe injury group, and 28 cases in the critical injury group. The serum PCT levels of patients in the mild injury group showed a continuous downward trend with the prolongation of admission time. The serum PCT levels in the severe injury and critical injury groups reached their peak at 3 days after admission, and were significantly higher than those in the mild injury group (μg/L: 3.53±0.68, 4.47±0.63 vs. 0.40±0.14, both P < 0.05), gradually decreasing thereafter, but still significantly higher than the mild injured group at 7 days. Kendall tau-b correlation analysis showed that there was a significant positive correlation between serum PCT levels on days 1, 3, 5, and 7 of admission and the severity of disease ( r value was 0.801, 0.808, 0.766, 0.528, respectively, all P < 0.01). As of October 30, 2022, 92 out of 120 patients with traumatic brain injury survived and 28 died, with a mortality of 23.33%. Compared with the survival group, the GCS score, serum interleukin-6 (IL-6) levels, white blood cell count (WBC) in peripheral blood, and PCT levels in cerebrospinal fluid at admission in the death group were significantly increased [GCS score: 5.20±0.82 vs. 4.35±0.93, IL-6 (ng/L): 1.63±0.45 vs. 0.95±0.27, blood WBC (×10 9/L): 14.31±2.03 vs. 11.95±1.98, PCT in cerebrospinal fluid (μg/L): 11.30±1.21 vs. 3.02±0.68, all P < 0.01]. The serum PCT levels of patients in the survival group showed a continuous downward trend with prolonged admission time. The serum PCT level in the death group peaked at 3 days after admission and was significantly higher than that in the survival group (μg/L: 4.11±0.62 vs. 0.52±0.13, P < 0.01), gradually decreasing thereafter, but still significantly higher than the survival group at 7 days. Cox regression analysis showed that serum IL-6 levels [hazard ratio ( HR) = 17.347, 95% confidence interval (95% CI) was 5.874-51.232], WBC in peripheral blood ( HR = 1.383, 95% CI was 1.125-1.700), PCT levels in cerebrospinal fluid ( HR = 1.952, 95% CI was 1.535-2.482) at admission and serum PCT levels on admission days 1, 3, 5, and 7 [ HR (95% CI) was 6.776 (1.844-24.906), 1.840 (1.069-3.165), 3.447 (1.284-9.254), and 6.666 (1.214-36.618), respectively] were independent risk factors for death during follow-up in patients with traumatic brain injury (all P < 0.05). ROC curve analysis showed that the AUC of serum PCT levels on days 1, 3, 5, and 7 for predicting death during follow-up in patients with traumatic brain injury was all > 0.8 [AUC (95% CI) was 0.898 (0.821-0.975), 0.800 (0.701-0.899), 0.899 (0.828-0.970), 0.865 (0.773-0.958), respectively], indicating ideal predictive value. The optimal cut-off value for serum PCT level at 3 days of admission was 1.88 μg/L, with the sensitivity of 78.6% and specificity of 88.0% for predicting death during follow-up. Conclusions:Abnormal expression of serum PCT levels in patients with traumatic brain injury on the 3rd day of admission was found. The serum PCT levels greater than 3 μg/L may be related to severe illness. The serum PCT levels greater than 1.88 μg/L can predict the poor prognosis of patients. Dynamic observation of changes in serum PCT levels has good evaluation value for the severity and prognosis of patients with traumatic brain injury in plateau areas.

Objective To investigate the compatibility between antiepileptic active pharmaceutical ingredient(API)levetiracetam and binder polyethylene glycol 6000,and provide a basis for evaluating and ensuring the safety of drugs.Methods Levetiracetam and polyethylene glycol 6000 from different producers were mixed in a certain proportion,and placed under different conditions according to the test method of stability influencing factors.The compatibility of levetiracetam and polyethylene glycol 6000 was analyzed by differential scanning calorimetry and HPLC,respectively,and the thermal variations,changes of levetiracetam appearance and related substances were investigated.Results After being placed under high humidity(relative humidity of 90％)and light(4 500 Lx)for 10 days,the compatibility between API and pharmaceutical excipients was proved good,while under the conditions of high temperature of 50℃ and 60℃,polyethylene glycol 6000 interacted with levetiracetam,resulting in the growth of levetiracetam related substances including impurity A and total amount of impurities,along with the production of two unknown impurities.Polyethylene glycol 6000 from different producers and different batches had different effects on the related substances of levetiracetam.Conclusion There is a risk of compatibility between levetiracetam and polyethylene glycol 6000 under elevated temperatures,and it is recommended that preparation producers optimize product prescriptions and improve the quality and safety of drugs.