ObjectiveThis study aims to explore the mechanism by which Yishen Huoxue Tongqiao Formula improves metabolism-neuroplasticity and treats unilateral vestibular labyrinth destruction by regulating the metabolic balance of glutamate （Glu）/γ-aminobutyric acid （GABA）. Methods48 Sprague-Dawley （SD） adult rats were randomly divided into the sham operation group， model group， Yishen Huoxue Tongqiao Formula groups with low， medium， and high doses （9.20， 18.39， 36.78 g·kg^-1）， and betahistine group （1.62 mg·kg^-1）. A unilateral vestibular labyrinth destruction （vestibular dysfunction） model was established by intratympanic injection of chloroform into the right ear， while the control group received intratympanic injection of normal saline. Drugs were administered once daily for seven consecutive days. During the period， behavioral tests were performed to evaluate the behaviors of rats after unilateral vestibular labyrinth destruction. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe the neuronal morphology in the medial vestibular nucleus. Golgi staining was employed to assess the number of dendritic spines of neurons in the medial vestibular nucleus. Ultra-performance liquid chromatography-tandem mass spectrometry （LC-ESI-MS/MS） was utilized to detect Glu/GABA. Immunofluorescence and immunohistochemistry were used to detect the expressions of neuronal nuclei （NeuN）， growth-associated protein 43 （GAP-43）， and glial fibrillary acidic protein （GFAP）. Western blot and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were applied to determine the expressions of glutamate-immunoreactive （Glu-IR）， GABA， GFAP， postsynaptic density protein 95 （PSD-95）， and GAP-43. ResultsCompared with the sham operation group， the model group presented with head deviation， balance disorder， increased tail suspension score， nuclear consolidation of medial vestibular nerve neurons， and decreased Nissl bodies （P<0.01）. The number of dendritic spines in neurons and NeuN-positive cells decreased. The content of Glu decreased. The content of GABA increased （Glu/GABA decreased）. The expression of GAP-43 was down-regulated， and GFAP was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PSD-95， and GAP-43 proteins， as well as Glu-IR mRNA decreased， while the expressions of GABA and GFAP proteins and mRNA increased （P<0.05， P<0.01）. Compared with those in the model group， the head deviation， imbalanced behavior， and tail suspension scores in each treatment group decreased， with alleviated neuronal injury and recovered Nissl bodies （P<0.01）. The number of dendritic spines of neurons increased， and the number of NeuN-positive cells rebounded. The content of Glu increased， and the content of GABA decreased （Glu/GABA increased）. GFAP was down-regulated， and GAP-43 was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PMD-95， and GAP-43 proteins， as well as Glu-IR mRNA increased， while the expressions of GABA and GFAP proteins and mRNA decreased. The effect was more significant in the high-dose group （P<0.01）. ConclusionThe Yishen Huoxue Tongqiao Formula can alleviate vestibular dysfunction， and its mechanism may be associated with regulating the metabolic balance of Glu/GABA， mitigating neural damage， improving synaptic plasticity （promoting GAP-43 expression and inhibiting GFAP expression）， and facilitating vestibular compensation.

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg^-1）， a low-dose group of Shuanghua drink （7.14 mL·kg^-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg^-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg^-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg^-1）， a low-dose group of Shuanghua drink （4.28 mL·kg^-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg^-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg^-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F_2α （PGF_2α）， prostaglandin E₂ （PGE₂）， thromboxane B₂ （TXB₂）， prostacyclin metabolite （6-keto-PGF_1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF_2α/PGE₂ （P<0.01）， TXB₂/6-keto-PGF_1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）. ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg^-1）， a low-dose group of Shuanghua drink （7.14 mL·kg^-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg^-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg^-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg^-1）， a low-dose group of Shuanghua drink （4.28 mL·kg^-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg^-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg^-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F_2α （PGF_2α）， prostaglandin E₂ （PGE₂）， thromboxane B₂ （TXB₂）， prostacyclin metabolite （6-keto-PGF_1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF_2α/PGE₂ （P<0.01）， TXB₂/6-keto-PGF_1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）. ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

OBJECTIVES: To study clinical manifestations and gene mutation features of neonates with centronuclear myopathy. METHODS: A retrospective analysis was conducted on the medical data of 5 neonates with centronuclear myopathy diagnosed in the Neonatal Intensive Care Unit of Children's Hospital, Zhejiang University School of Medicine from January 2020 to August 2024. The data included gender, gestational age, birth weight, Apgar score, clinical manifestations, creatine kinase level, electromyography, genetic testing results and the outcomes of the infants. RESULTS: All 5 male neonates had a history of postpartum asphyxia and resuscitation. They all presented with hypotonia, myasthenia, and respiratory failure; two neonates also had swallowing dysfunction. Of the five neonates, three had normal creatine kinase levels, while two had slightly elevated levels. Electromyography was performed for three neonates, among whom two had myogenic damage. MTM1 gene mutations were identified by genetic testing in all five neonates, including two nonsense mutations and three missense mutations, among which one variant had not been previously reported. Four mutations were inherited from the mother, and the other one was a de novo mutation. The five neonates showed no clinical improvement following treatment, failed weaning from mechanical ventilation, and ultimately died after withdrawal of life-sustaining therapy. CONCLUSIONS Centronuclear myopathy caused by MTM1 gene mutation often has a severe phenotype and a poor prognosis, and it should be considered for neonates with hypotonia and myasthenia after birth. Genetic testing should be performed as soon as possible.
Humans ; Myopathies, Structural, Congenital/genetics* ; Male ; Infant, Newborn ; Retrospective Studies ; Mutation ; Female ; Protein Tyrosine Phosphatases, Non-Receptor/genetics*

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Objective:To assess the efficacy and safety of overlapping braided carotid artery stent (Wallstent) implantation in large extracranial internal carotid artery aneurysms (15 mm≤diameter<25 mm) and giant ones (diameter≥25 mm).Methods:A retrospective study was performed; the clinical data of 23 patients with large or giant extracranial internal carotid artery aneurysms accepted overlapping Wallstent stent implantation in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from August 2015 to June 2023 were collected. Immediately after implantation, DSA was used to evaluate the retention of contrast agent within the aneurysms and high-resolution C-arm CT (HR-CBCT) was used to detect the apposition between the two stents and between the stents and inner wall of the blood vessel. Perioperative complications were recorded. Clinical follow-up was performed bi-monthly via outpatient visits or telephone, and modified Rankin scale (mRS) was used to assess the prognoses (mRS scores of 0-2 as good prognosis) at the last follow-up; aneurysm occlusion was evaluated in a 6-month follow-up by DSA and in-stent restenosis in a final imaging follow-up by DSA or CTA according to the OKM grading. Results:Twenty-two patients had successful overlapping implantation of 2 Wallstent stents; blood flow was restricted in one patient due to carotid artery dissection at the distal end of the aneurysm during stent implantation and restored after a Neuroform EZ stent and 2 Wallstent stent implantation from the distal-proximal lesion; technical success rate of 95.7% (22/23) was obtained. DSA immediately after implantation showed obvious contrast medium retention in all aneurysms. HR-CBCT indicated good stent apposition in 21 patients and mild incomplete stent apposition in 2. Clinical follow-up was finished in 23 patients, ranged 6-31 months (mean 11.5±6.3 months); all patients had good prognosis at the last follow-up. Imaging follow-up, including at least once DSA, was conducted for all patients, with intervals ranging from 6 to 15 months (mean 10.4±3.4 months); DSA 6 months after implantation showed complete aneurysm occlusion in 19 patients (OKM grading D) and a bit of residual contrast in 4 patients (OKM grading C); final imaging follow-up (DSA in 2 and CTA in 21) revealed in-stent stenosis in 2 patients (stenosis rates of 51% and 87%) with obvious improved stenosis after balloon angioplasty and patent stents in 21 patients without evidence of aneurysm opacification.Conclusion:Overlapping braided carotid artery stent (Wallstent) implantation is an effective and safe approach for managing large or giant extracranial carotid artery aneurysms.

Objective To analyze the incidence and mortality of malignant tumors among the middle-aged and elderly population in Chengguan district of Lanzhou from 2011 to 2021,and to discuss the related risk factors.Methods Using the research data of REACTION in Lanzhou,an epidemiological survey was conducted through cluster sampling in three communities in Chengguan district of Lanzhou since April 2011.The target population was middle-aged and elderly residents over 40 years old.Two follow-up surveys were carried out in 2014-2016 and 2021 successively,and 6543 people with complete follow-up data were finally included.The incidence and mortality rates of malignant tumors were calculated,as well as their age standardized rates with reference to the age composition of Segi's world standard population.Multivariate Cox regression analysis was used to screen the risk factors affecting the incidence and mortality of malignant tumors.Results After an average follow-up of 10.6 years,314 new cases of malignant tumors were found in middle-aged and elderly residents in Chengguan district of Lanzhou,with an incidence rate and age standardized incidence rate of 454.30/100 000 and 128.93/100 000,respectively.A total of 158 deaths were attributed to malignant tumors,with a mortality rate and age standardized rate of 228.41/100 000 and 607.9/100 000,respectively;The age standardized incidence rate and mortality rate of malignant tumors males were both higher than those females(P＜0.05).During the follow-up period,the age standardized incidence rate of malignant tumors in the general population showed an significant upward trend(P＜0.05),whereas the age standardized mortality rate gradually decreased after a brief increase(P＜0.05).Lung cancer,colorectal cancer,gastric cancer,and liver cancer were the main types of malignant tumors ranking in the top five in terms of incidence and mortality by gender.Multivariate Cox regression results indicate that male,age≥60 years old,college education level or above,smoking history,drinking history,having been hit by major stressful events,central obesity,hypertension,and coronary heart disease are risk factors for the onset or death of malignant tumors(HR＞1).Married,with family size≥4,frequent consumption of fresh fruit,frequent consumption of fresh vegetables,frequent consumption of grains and tubers are protective factors for the onset or death of malignant tumors(HR＜1).Conclusion The incidence of malignant tumors among middle-aged and elderly people in Chengguan district of Lanzhou from 2011 to 2021 showed an increasing trend,while the overall mortality was decreasing.Our study indicates early cancer screening in elderly populations,maintaining a healthy lifestyle and strengthening the management of chronic diseases are crucial for the prevention and treatment of malignant tumors.

Objective:To explore the association between cognitive function and the level of gamma-amino-butyric acid(GABA)in anterior cingulate cortex(ACC)before and after treatment in patients with major depres-sion disorder.Methods:Totally 31 medication-naive patients with major depression disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)and 33 normal controls were col-lected.Each eligible patient received treatment with selective serotonin reuptake inhibitor agents for 8 weeks.The MATRICS Consensus Cognitive Battery(MCCB)was used to evaluate the cognitive function.By means of 1H magnetic resonance spectroscopy,anterior cingulate cortex GABA concentrations were measured.Results:At base-line,the concentration of ACC GABA relative to water(GABA+/W)was lower in the patient group than in the control group(P＜0.05)and increased after treatment(P＜0.05).ACC GABA+/W was negatively associated with verbal learning and visual memory score in patient group at baseline(correlation coefficient and P value were r=-0.40,P＜0.05;r=-0.42,P＜0.05,respectively).The ACC GABA+/W difference resulted of treatment in patient group was positively associated with the difference of working memory score and the difference of reasoning and problem-solving score(correlation coefficient and P value were r=0.58,P＜0.05;r=0.66,P＜0.05,respec-tively).Conclusion:The cognitive dysfunction of patients with major depression disorder may not be related to the degree of depression and anxiety.And improvement of cognitive function may be associated with increase of ACC GABA concentrations.