Objective: To investigate the effects of fine particulate matter (PM2.5) exposure on acute myocardial infarction (AMI) mortality and years of life lost (YLL). Methods: Mortality data in Haizhu District, Guangzhou City from 2020 to 2024 were collected by the China Population Death Information Registration Management System and Guangdong Death Certificate Management System. Air pollution and meteorological data of the same period were obtained from the national environmental monitoring sites on the National Real-time Air Quality Release Platform and the Guangzhou Observatory, respectively. The single-pollutant model and multi-pollutant model were established by distributed lag non-linear model to analyze the effects of PM2.5 on AMI mortality and YLL. Results: From 2020 to 2024, there were 2 466 AMI death cases in Haizhu District, including 949 males and 1 517 females. Among them, 530 cases were aged <65 years, 494 cases were aged 65-74 years, and 1 442 cases were aged >74 years. The median daily average number of deaths was 1.3 (interquartile range, 2.0) cases, and the median daily average YLL was 16.4 (interquartile range, 24.8) person years. The median daily average mass concentration of PM2.5 was 24.3 (interquartile range, 18.0) μg/m3. In single-pollutant models, the maximum effects of PM2.5 on AMI mortality and YLL were observed at a cumulative lag of 7 days. For per 10 μg/m3 increment in the daily average concentration of PM2.5, the excess risk of AMI mortality increased by 8.793% (95%CI: 4.201% to 13.588%), and YLL increased by 2.059 (95%CI: 1.081 to 3.037) person-years. Gender-stratified analyses showed that PM2.5 significantly affected AMI mortality in males and YLL in males and females (all P<0.05). Age-stratified analyses revealed that PM2.5 significantly affected AMI mortality and YLL among residents aged <65 years and 65-74 years (all P<0.05). However, the difference between genders or the two age groups was not statistically significant (both P>0.05). In multi-pollutant models, when NO2, SO2, or O3 were introduced respectively at a cumulative lag of 7 days, the effects of PM2.5 on AMI mortality and YLL were enhanced compared to the single-pollutant model (all P<0.05). When PM10 was introduced alone or in combination with PM10, SO2, NO2, and O3, the effects of PM2.5 on AMI mortality and YLL were not statistically significant (all P>0.05). Conclusion Exposure to PM2.5 may increase the risk of AMI mortality and YLL, with varying effects across populations of different genders and ages.

OBJECTIVE: To investigate the effectiveness of Youngswick-Akin osteotomy in the treatment of moderate hallux valgus combined with mild to moderate hallux rigidus. METHODS: The clinical data of 43 patients with moderate hallux valgus combined with mild to moderate hallux rigidus who were admitted between August 2019 and August 2022 and met the selection criteria were retrospectively analyzed. There were 8 males and 35 females. The age ranged from 28 to 77 years, with an average age of 59.0 years. The disease duration ranged from 10 to 35 months, with an average of 20 months. The degree of hallux rigidus included 2 cases of CoughlinⅠ degree, 29 cases of Ⅱ degree, 12 cases of Ⅲ degree. The preoperative hallux valgus angle ranged from 25° to 40°, with an average of 32°. All patients were treated with Youngswick-Akin osteotomy. The first metatarsophalangeal joint space was compared before operation and at 6 months after operation. The American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analogue scale (VAS) score were used to evaluate the functional recovery and pain relief of the patients before operation and at 6 and 24 months after operation. According to the severity of hallux rigidus, the patients were divided into mild group (Ⅰ, Ⅱ degree) and moderate group (Ⅲ degree) to compare the prognosis, including the changes of AOFAS score, VAS score, and the first metatarsophalangeal joint space. RESULTS: The operation time was 60-75 minutes (mean, 65 minutes). The intraoperative blood loss was 10-30 mL (mean, 20 mL). Two cases had superficial infection of the incision margin after operation, and healed well after dressing change and antibiotic treatment. The incisions of the other patients healed by first intention, and no medial cutaneous nerve injury of the great toe occurred. All patients were followed up 24-31 months, with an average of 25.8 months. The patient's hallux valgus deformity was corrected without recurrence; no complication such as osteomyelitis and hallux varus occurred. The AOFAS score, VAS score, and the first metatarsophalangeal joint space after operation significantly improved when compared with those before operation, the AOFAS score and VAS score at 24 months after operation further improved when compared with those at 6 months after operation, and the differences were significant ( P<0.05). The change of VAS score in mild group was significantly better than that in moderate group ( P<0.05); but there was no significant difference in the changes of AOFAS score and the first metatarsophalangeal joint space between the two groups ( P>0.05). CONCLUSION Youngswick-Akin osteotomy for moderate valgus deformity with mild to moderate hallux rigidus can achieve good functional recovery, pain relief, and joint space improvement.
Humans ; Osteotomy/methods* ; Hallux Valgus/diagnostic imaging* ; Male ; Female ; Middle Aged ; Hallux Rigidus/diagnostic imaging* ; Retrospective Studies ; Adult ; Aged ; Treatment Outcome ; Metatarsophalangeal Joint/surgery*

Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective To investigate the expression of PIK3CA,phosphorylated protein kinase B(p-AKT)and phosphatase and tensin homologue deleted on chromosome 10(PTEN)in sinonasal squamous cell carcinoma(SNSCC).Methods The expressions of PIK3CA and PTEN in head and neck squamous cell carci-noma(HNSCC)were analyzed through the data set of HNSCC in the cancer genome map of UCSC Xena data-base.The immunohistochemical SP method was used to measure the expression of PIK3CA,p-AKT and PTEN in 43 cases of SNSCC tissues,20 cases of normal inferior concha tissues.The relationship between the expressions of PIK3CA,p-AKT and PTEN protein with the clinicopathological features and prognosis of the patients with SNSCC was analyzed.Results The results of bioinformatic analysis showed that PIK3CA mR-NA expression in HNSCC tissues was higher than that in paracancerous tissues(P＜0.01),while the PTEN mRNA expression was lower than that in paracancerous tissues(P＜0.05).The immunohistochemical detec-tion results showed that the positive expressions rates of PIK3CA and p-AKT proteins in normal nasal mucosa tissues were significantly lower than those in SNSCC tissues,while the positive expression rate of PTEN pro-tein in SNSCC tissues was significantly higher than that in normal inferior nasal concha mucosa tissues,and the differences were statistically significant(P＜0.01).The expressions of PIK3CA and p-AKT protein were related to the clinical stage,differentiation degree and primary site(P＜0.05),but were not related to age,gender,smoking and drinking(P＞0.05);the PTEN protein expression was not related with the clinical stage,differentiation degree,primary site,age,smoking and drinking(P＞0.05).The Spearman analysis showed that the expression of PIK3CA in SNSCC tissues was positively correlated with p-AKT protein ex-pression(r=0.664,P＜0.01),and PIK3CA was negatively correlated with PTEN protein(r=-0.414,P＜0.01).The expression of p-AKT was negatively correlated with PTEN protein(r=-0.453,P＜0.01).The Kaplan-Meier analysis showed that the median survival time of the patients with PIK3CA and p-AKT protein positive expression was shorter than that of the patients with negative expression(P＜0.01).There was no statistically significant difference in median survival between the patients with PTEN protein positive expres-sion and those with negative expression.Conclusion The overexpressions of PIK3CA and p-AKT accompa-nied by the loss of PTEN expression participate in the development and progression of SNSCC,moreover the PIK3CA and p-AKT expressions are related to the poor prognosis of the patients.

Objective:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.

Objective To compare the effect of palliative mitral valve surgeries and medication therapies for secondary non-ischemic mitral regurgitation. Methods The clinical data of patients with non-ischemic functional mitral regurgitation treated in our hospital between 2009 and 2019 were retrospectively analyzed. Patients with a left ventricular ejection fraction (LVEF)＜40% underwent a dobutamine stress test, and a positive result was determined when the LVEF improved by more than 15% compared to the baseline value. Positive patients were divided into a surgery group and a medication group. The surgery group underwent surgical mitral valve repair or replacement, while the medication group received simple medication treatment. Follow-up on survival and cardiac function status through outpatient or telephone visits every six months after surgery, and patients underwent cardiac ultrasound examination one year after surgery. The main research endpoint was a composite endpoint of all-cause death, heart failure readmission, and heart transplantation, and the differences in cardiac function and cardiac ultrasound parameters between the two groups were compared. Results Ultimately 41 patients were collected, including 28 males and 13 females with an average age of 55.5±11.1 years. Twenty-five patients were in the surgery group and sixteen patients in the medication group. The median follow-up time was 16 months, ranging 1-96 months. The occurrence of all-cause death in the surgery group was lower than that in the medication group (HR=0.124, 95%CI 0.024-0.641, P=0.034). The difference between the two groups was not statistically significant in the composite endpoint (HR=0.499, 95%CI 0.523-1.631, P=0.229). The New York Heart Association (NYHA) grade of the surgery group was better (NYHA Ⅰ-Ⅱ accounted for 68.0% in the surgury group and 18.8% in the medication group, P<0.01) as well as the grade of mitral valve regurgitation (87.5% of the patients in the medication group had moderate or above regurgitation at follow-up, while all the patients in the surgery group had moderate below regurgitation, P<0.01). There was no statistical difference in preoperative and follow-up changes in echocardiograph parameters between the two groups (P＞0.05). Conclusion For non-ischemic functional mitral regurgitation, if the cardiac systolic function is well reserved, mitral valve surgery can improve survival and quality of life compare to simple medication therapy.

In the context of high-quality development in medical institutions, the supply-processing-distribution(SPD) management mode has gradually been widely applied. The authors described in detail the procurement, supply, inventory, distribution, and settlement management of medical consumables and in vitro diagnostic reagents in a certain hospital under the SPD mode. It was found that SPD was conducive to strengthening the supervision of medical consumables and in vitro diagnostic reagents in the hospital, ensuring quality and safety of use, reducing hospital operating costs, and improving hospital′s competitiveness. However, attention should be paid to preventing data security risks, strengthening operational management, and improving the cost-benefit analysis of in vitro diagnostic reagents.

Objective To explore the diagnostic value of alkaline phosphatase on the surface membrane of neutrophils(mNAP)in bloodstream infections(BSI)of Gram-negative bacteria(GNB)and Gram-positive bacteria(GPB).Methods A total of 418 patients diagnosed with BSI at Donghai People's Hospital from January 2022 to December 2023 were enrolled in the study.Based on the results of Gram staining from positive blood cultures,the patients were divided into GNB bacteremia(n=329)and GPB bacteremia(n=89).Additionally,35 hospitalized patients with systemic inflammatory response syndrome(SIRS)during the same period were selected as the control group.Their clinical data,routine laboratory test results,blood cultures and venous blood samples were collected,and the expression levels of mNAP were detected by flow cytometry.The receiver operating characteristics(ROC)curve was used to evaluate the diagnostic performance of mNAP for BSI of GNB and GPB.Results The expression levels of mNAP in the GPB infection,GNB infection and SIRS groups were 9 588(5 677,11 343)AB/C,16 616(11 853,22 035)AB/C,and 5 738(2 613,9 178)AB/C,respectively,and the difference among them was statistically significant(H=43.95,P＜0.000 1).Further pairwise comparisons showed that the expression levels of mNAP in the GNB infection group were significantly higher than those in the GPB infection group(U=203.0,P＜0.000 1)and the SIRS group(U=445.0,P＜0.000 1).Meanwhile,the expression levels of mNAP in the GPB infection group were significantly higher than that in the SIRS group(U=583.0,P＜0.000 1).The area under the ROC curve(AUCROC)of mNAP for predicting the BSI of GNB was 0.91(95%CI:0.85-0.96).When the cut-off value was 10 820 AB/C,its sensitivity and spe-cificity were 80.00%and 88.57%,respectively.The AUCROC of mNAP for predicting the BSI of GPB was 0.69(95%CI:0.55-0.83).When the cut-off value was 10 859 AB/C,its sensitivity and specificity were 33.00%and 88.13%,respectively.Conclusion The di-agnostic efficiency of mNAP for the BSI of GNB is significantly higher than that for the BSI of GPB,which may become a novel biologi-cal marker for distinguishing the BSI of GNB and GPB.

Objective:To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple myeloma.Methods:A total of 96 patients with newly diagnosed multiple myeloma (NDMM) between July 31, 2020, and December 31, 2022, were retrospectively analyzed, of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode. After hematopoietic stem cells were mobilized and collected, melphalan was started immediately for pre-transplant conditioning, and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning. The control group consisted of 55 patients who received traditional transplantation mode. After hematopoietic stem cells were collected, stem cell cryopreservation was performed in liquid nitrogen, and then the transplant plans were started at the right time. All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor.Results:① A total of 34 patients (82.9% ) with VGPR plus CR in the observation group were significantly higher than 33 patients (60.0% ) in the control group ( P=0.016). ②Compared with the control group, the incidence of grade 1 oral mucosal inflammation was higher in the observation group ( P<0.001) ; however, the incidence of grades 2 and 3 oral mucosal inflammation was lower ( P=0.004, P=0.048), and neither group experienced grade 4 or above oral mucosal inflammation. The incidence of grade 1 diarrhea was higher in the observation group ( P=0.002), whereas the incidence of grade 3 diarrhea was lower ( P=0.007). No statistically significant difference was observed in the incidence of grade 4 diarrhea ( P=0.506), and neither group experienced grade 5 diarrhea. ③ The incidence of bacterial infection in the observation group was lower than that in the control group (34.1% vs 65.5%, P=0.002), whereas no statistically significant difference was observed in the incidence of fungal infection (29.3% vs 31.4%, P=0.863) and viral infection (4.88% vs 3.64%, P=0.831). ④No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups [10 (8-20) days vs 11 (8-17) days, P=0.501; 13 (10-21) days vs 15 (10-20) days, P=0.245]. ⑤ All patients did not receive lenalidomide treatment 100 days post-transplantation. At 30 days post-transplantation, the CTL, NK, and Th cell counts in the observation group were lower than those in the control group ( P<0.001, P=0.002, P=0.049), and the NKT cell counts were higher than those in the control group ( P=0.024). At 100 days post-transplantation, the CTL, NKT, and Th cell counts in the observation group were higher than those in the control group ( P=0.025, P=0.011, P=0.007), and no statistically significant difference in NK cell counts was observed between the two groups ( P=0.396). ⑥ The median follow-up was 18 (4-33) months. The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5% and 78.2%, respectively ( P=0.337). The recurrence-free survival rates were 85.3% and 77.6%, respectively ( P=0.386), and the cumulative recurrence rates were 9.8% and 16.9%, respectively ( P=0.373) . Conclusion:In NDMM, the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models, with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.

Objective:To explore the protective effects of Zhenzhu Tongluo Pills on cerebral ischemia reperfusion injury in rats.Methods:Totally 15 healthy SD rats were randomly divided into sham-operation group, model group and TCM group according to random number table method, with 5 rats in each group. Except for the sham-operation group, cerebral ischemia models in the other two groups were induced by temporary middle cerebral artery occlusion. After the establishment of ischemia models, the TCM group was administered Zhenzhu Tongluo Pills solutions (1 ml/100 g) intragastrically at a dose of 0.5 g/(kg·d), and the sham-operation group and model group were treated with normal saline, for 14 consecutive days. Neurological deficit score was used to evaluate the degree of neurological deficit in cerebral ischemia rats. TTC staining were used for determining the infarct weights. The nerve cell damage was observed using HE staining method. Immunohistochemistry staining was used to observe the expression levels of GFAP, Nestin, and NeuN.Results:Compared with that at the 3 hours after reperfusion, the Bederson score in the TCM group decreased at the 30 minutes after the last administration ( P<0.05); compared with the model group, the infarction ratio of rats in the TCM group decreased ( P<0.05); the NeuN staining of neurons around the ischemic lesion in the model group rats was light, while Nestin and GFAP staining were deep; the Nestin and GFAP staining of neurons in the TCM group was light, while NeuN staining was deeper. Conclusion:Zhenzhu Tongluo Pills can improve the symptom of neurological deficits, reduce the volume of infarction, and protect neurons from injury in rats with cerebral ischemia.