ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen （TFCC） in the mouse model of chronic unpredictable mild stress （CUMS）. MethodsFifty male 4-week-old ICR mice were randomized into five groups （n=10 per group）： blank control， model， Cuscutae Semen decoction （10.2 g·kg^-1·d^-1）， paroxetine （2.6 mg·kg^-1·d^-1）， and TFCC （173.2 mg·kg^-1·d^-1）. The other groups except the blank control group underwent chronic unpredictable mild stress （CUMS） for 4 weeks. Behavioral assessments were conducted post-modeling. Then， the model group received distilled water （10 mL·kg^-1·d^-1）， while treatment groups were administrated with respective agents via oral gavage （10 mL·kg^-1） for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test （SPT）， forced swimming test （FST）， and tail suspension test （TST）. Hippocampal neuronal morphology was observed via hematoxylin-eosin staining， and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the hippocampal levels of inflammatory cytokines ［interleukin （IL）-1β， IL-6， and TNF-α）］ and neurotransmitters ［5-hydroxytryptamine （5-HT）， dopamine （DA）， and brain-derived neurotrophic factor （BDNF）］， while the reactive oxygen species （ROS） levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated Speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， and inducible nitric oxide synthase （iNOS）. Western blot was employed to evaluate the protein levels of NLRP3， ASC， Caspase-1， uncoupling protein 2 （UCP2）， and thioredoxin-interacting protein （TXNIP）. ResultsCompared with the blank control group， the model group exhibited weight loss （P<0.01）， reduced sucrose preference （P<0.01）， prolonged immobility time in FST and TST （P<0.01）， neuron disarrangement with nuclear pyknosis in hippocampal CA3 region， increased apoptosis in the brain tissue， elevated levels of IL-1β， IL-6， and TNF-α （P<0.01）， declined levels of 5-HT， DA， and BDNF （P<0.01）， increased ROS accumulation （P<0.01）， upregulated mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， down-regulated protein level of UCP2 （P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Compared with the model group， the interventions restored sucrose preference （P<0.01）， shortened immobility time （P<0.01）， repaired hippocampal neuronal structure， reduced apoptosis， lowered the levels of inflammatory cytokines （P<0.01）， restored the levels of neurotransmitters （P<0.01）， alleviated ROS accumulation （P<0.01）， downregulated the mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， upregulated the protein level of UCP2 （P<0.01）， and reduced the protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Moreover， TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair， neurotransmitter regulation， anti-inflammatory effects， and modulation of the UCP2/TXNIP/NLRP3 pathway （P<0.05）. ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation， reduce oxidative stress， restore neurotransmitters， thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen （TFCC） in the mouse model of chronic unpredictable mild stress （CUMS）. MethodsFifty male 4-week-old ICR mice were randomized into five groups （n=10 per group）： blank control， model， Cuscutae Semen decoction （10.2 g·kg^-1·d^-1）， paroxetine （2.6 mg·kg^-1·d^-1）， and TFCC （173.2 mg·kg^-1·d^-1）. The other groups except the blank control group underwent chronic unpredictable mild stress （CUMS） for 4 weeks. Behavioral assessments were conducted post-modeling. Then， the model group received distilled water （10 mL·kg^-1·d^-1）， while treatment groups were administrated with respective agents via oral gavage （10 mL·kg^-1） for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test （SPT）， forced swimming test （FST）， and tail suspension test （TST）. Hippocampal neuronal morphology was observed via hematoxylin-eosin staining， and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the hippocampal levels of inflammatory cytokines ［interleukin （IL）-1β， IL-6， and TNF-α）］ and neurotransmitters ［5-hydroxytryptamine （5-HT）， dopamine （DA）， and brain-derived neurotrophic factor （BDNF）］， while the reactive oxygen species （ROS） levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated Speck-like protein containing a CARD （ASC）， cysteinyl aspartate-specific proteinase-1 （Caspase-1）， IL-1β， and inducible nitric oxide synthase （iNOS）. Western blot was employed to evaluate the protein levels of NLRP3， ASC， Caspase-1， uncoupling protein 2 （UCP2）， and thioredoxin-interacting protein （TXNIP）. ResultsCompared with the blank control group， the model group exhibited weight loss （P<0.01）， reduced sucrose preference （P<0.01）， prolonged immobility time in FST and TST （P<0.01）， neuron disarrangement with nuclear pyknosis in hippocampal CA3 region， increased apoptosis in the brain tissue， elevated levels of IL-1β， IL-6， and TNF-α （P<0.01）， declined levels of 5-HT， DA， and BDNF （P<0.01）， increased ROS accumulation （P<0.01）， upregulated mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， down-regulated protein level of UCP2 （P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Compared with the model group， the interventions restored sucrose preference （P<0.01）， shortened immobility time （P<0.01）， repaired hippocampal neuronal structure， reduced apoptosis， lowered the levels of inflammatory cytokines （P<0.01）， restored the levels of neurotransmitters （P<0.01）， alleviated ROS accumulation （P<0.01）， downregulated the mRNA levels of NLRP3， ASC， Caspase-1， IL-1β， and iNOS （P<0.01）， upregulated the protein level of UCP2 （P<0.01）， and reduced the protein levels of NLRP3， ASC， Caspase-1， and TXNIP （P<0.01）. Moreover， TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair， neurotransmitter regulation， anti-inflammatory effects， and modulation of the UCP2/TXNIP/NLRP3 pathway （P<0.05）. ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation， reduce oxidative stress， restore neurotransmitters， thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.

BACKGROUND:Hydroxyapatite is the main inorganic component of bone tissue.The polymer has the structure and function of a biomimetic extracellular matrix.The composites of hydroxyapatite and polymer have been widely studied. OBJECTIVE:To summarize the research status of hydroxyapatite composite polymer materials for bone tissue repair. METHODS:The articles collected in PubMed,Web of Science,CNKI and WanFang databases were searched from January 2010 to April 2023.The Chinese and English search terms were"hydroxyapatite,polymer,composites,degradability,bone defect,bone repair".Finally,75 articles were included for review. RESULTS AND CONCLUSION:Polymers often used in composite with hydroxyapatite for bone tissue repair include natural polymers(collagen,chitosan,alginate,serine protein,cellulose,hyaluronic acid,and polyhydroxybutyrate)and synthetic polymers[polylactic acid,polylactic acid-hydroxyacetic acid copolymer,poly(has-lactide),poly(amino acid)and poly(vinyl alcohol)].The mechanical properties and osteoinductivity of hydroxyapatite/polymer composites were improved compared with pure hydroxyapatite.Hydroxyapatite composite with polymers can be made into porous scaffolds,hydrogels,and coatings for bone repair.Hydroxyapatite/polymer composites can accelerate bone reconstruction with a slow release of loaded drugs and cytokines due to their bionic extracellular matrix structure and function.Based on the diversity of causes of bone defects and the fact that bone repair is a complex continuous process involving multiple biological factors and proteins,repair materials with mechanical properties matching bone tissue,degradation processes synchronized with bone repair,and efficient osteogenesis and vascularization need to be further investigated.

Objective To establish a fluoroscopic percutaneous vertebral augmentation model in dogs by measuring and analyzing canine spinal anatomy.We also assessed the effectiveness and safety of this modeling method by postoperative radiological analysis.Methods Morphological measurements were taken in six dogs,aged approximately 12～24 months,and the following parameters of the lumbar vertebrae were determined:height of the L1～L7 vertebrae,width of the vertebral base,distance from the upper edge of the intervertebral disc to the narrowest part of the vertebra,distance from the vertical line of the spinous process to the upper edge of the intervertebral disc,and vertical distance from the midpoint of the transverse process to the lower edge of the intervertebral disc.These measurements were obtained to clarify the anatomical characteristics of the canine vertebrae and determine the optimal location,direction,and depth for bone-cement injection.A percutaneous vertebral augmentation model was subsequently established in the L4,L5,and L6 vertebrae of six healthy Beagle dogs,weighing 20～25 kg.The dogs were euthanized 4 weeks post-surgery and examined radiologically.Primary observations included the surgical duration,postoperative distribution of the implanted bone cement,and integrity of the vertebral canal and anterior edge of the vertebrae.Results Anatomical observation of the canine vertebrae revealed that the vertebral height increased gradually from L1～L5 and then decreased from L5～L7.The width of the vertebral base increased consistently from L1～L7.The distance from the vertical line of the spinous process to the upper edge of the intervertebral disc showed an increasing trend from L1～L7(1.9～4.0 mm).The distance between the midpoint of the base of the transverse process and the lower edge of the intervertebral disc increased gradually from L1～L5(4.7～6.9 mm).There was no significant difference in the distance between the midpoint of the base of the transverse process and the lower edge of the intervertebral disc in the L4,L5,and L6 segments among the dogs(P=0.925).The midpoint of the root of the transverse process of the spine was taken as the puncture point,and the insertion direction and horizontal plane were at an angle of 20°～30°,with a head tilt of 5°～15° and a puncture depth of 1.2～1.5 cm.If the puncture was directed towards the caudal side of the vertebra,the angle of the needle tail was 30°～35°,with a penetration depth of 1.5～1.8 cm.This technique allowed the successful construction of a canine vertebral puncture surgical model.A total of 15 canine vertebral puncture surgical models were successfully created,with an average surgery time of 22.7±4.6 min(15～30 min)per vertebral segment.During surgery,one vertebral segment experienced spinal cord injury result ing in paralysis of the hind limbs and bowel and bladder incontinence.Two vertebral cortical bones fractured,but there were no deaths due to anesthesia or infection.Four weeks post-surgery,micro-computed tomography-based three-dimensional reconstructions consistently showed bone cement distributed within the trabecular bone of the canine vertebrae,with newly formed bone tissue enveloping the implanted material.There was no leakage,and no complications such as damage to the vertebral canal or the anterior wall of the vertebrae.Conclusions A safe and reliable canine vertebral augmentation puncture model can be successfully established based on the anatomy of the canine lumbar vertebrae(L4～L6)and using the midpoint of the base of the transverse process as a bony landmark.

Objective:To explore the mortality and risk factors for chronic obstructive pulmonary disease (COPD)-related mortality in patients with non-metastatic non-small cell lung cancer (NSCLC).Methods:This retrospective cohort study included patients aged 18-80 diagnosed with NSCLC between 2010 and 2019 from the Surveillance, Epidemiology and End Results (SEER) database. Cohort 1 enrolled 89 621 cases of non-metastatic NSCLC to calculate COPD-related mortality; Cohort 2 included 71 949 elderly patients with non-metastatic NSCLC to investigate the risk factors of COPD-related mortality in non-metastatic NSCLC patients using a competing risks model.Results:COPD-related mortality rate was 2.86% among non-metastatic NSCLC patients . COPD-related mortality rate increased with age, with a COPD-related mortality rate of 3.24% in patients aged 60 to <80 years, accounting for 90.9% of COPD related deaths in the whole age group with non-metastatic NSCLC. In the univariate competing risks model, advanced age, male, white race, squamous cell carcinoma, negative lymph node metastasis, no surgical treatment, radiotherapy, no chemotherapy, low-income population and single were identified as risk factors for COPD-related mortality. The multivariate competing risks model revealed that advanced age (70-74 years old: HR=1.24, 95% CI: 1.09-1.42; 75-79 years old: HR=1.23, 95% CI: 1.07-1.41), squamous cell carcinoma ( HR=1.75, 95% CI: 1.60-1.92), radiotherapy ( HR=1.58, 95% CI: 1.41-1.70) were independent risk factors for COPD-related mortality (all P<0.05). Conclusions:COPD-related mortality rate is high in non-metastatic NSCLC patients. Aged over 70 years old, squamous cell carcinoma and radiotherapy are risk factors for COPD-related death.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To study the surveillance results of soil-transmitted nematode (STN) disease at the national surveillance site in Nanchang City, so as to scientifically formulate prevention and control strategies for parasitic diseases in Nanchang City.Methods:From 2016 to 2020, in Nanchang County, the national surveillance site of STN disease in Nanchang City, no less than 1 000 fecal samples and 25 soil samples of permanent residents over 3 years of age were investigated annually. The improved Kato-Katz thick smear method was used to detect the eggs of STN in the population, species identification of hookworm was carried out by test-tube filter paper incubation, the Enterobius vermicularis eggs of 3 - 9 years old children were detected by cellophane anal swab method, and the soil samples were used to identify hookworm larvae and of Ascaris lumbricoides eggs. Results:The total infection rate of STN was 0.93% (47/5 054) from 2016 to 2020 in the national surveillance site of Nanchang City. The annual infection rates were 0.10% (1/1 000), 2.94% (30/1 021), 0.79% (8/1 008), 0.50% (5/1 002) and 0.29% (3/1 023), respectively; the infection rates of hookworm, Ascaris lumbricoides and Trichuris trichiura were 0.42% (21/5 054), 0.02% (1/5 054) and 0.49% (25/5 054), respectively. Totally 97.87% (46/47) of the infected persons were mild infection. The population distribution characteristics showed that there was significant difference in STN infection rate among different education levels (χ 2 = 18.06, P = 0.001), but there was no significant difference in infection rate among different sex, age and occupation (χ 2 = 0.92, 2.01, 13.60, P > 0.05). Among them, the infection rate of junior high school cultural was the highest (1.84%, 24/1 301). The culture of hookworm larvae showed that 90.48% (19/21) were Necator americanus; the infection rate of Enterobius vermicularis in 3 - 9 years old children, the contamination rate of soil hookworm larvae and Ascaris lumbricoides eggs, were all 0. Conclusion:STN disease shows a low prevalence trend at the national monitoring site in Nanchang City, Trichuris trichiura and hookworm are the key insect species for STN disease control in Nanchang City in the future.

Objective:To understand the epidemic characteristics of malaria in Nanchang, and provide a basis for timely adjustment of prevention and control strategies and measures after elimination of malaria in Nanchang.Methods:By retrospective analysis, the malaria case information and epidemiological case questionnaire reported in Nanchang from 2016 to 2020 were collected from the "China Disease Control and Prevention Information System Infectious Disease Report Information Management System" and "Parasitic DiseasePrevention and Control Information Special Report System". General situation of the cases, three distributions (time, region and population distributions) and the source of infection were described and statistically analyzed.Results:A total of 69 malaria cases were reported in Nanchang from 2016 to 2020, including 39 cases of falciparum malaria, 19 cases of vivax malaria, 9 cases of ovale malaria, 1 case of quartan malaria and 1 case of mixed infection. The onset time of 69 malaria cases was not seasonal, and cases were reported every month; they were distributed in 8 districts (counties) of Nanchang, with Jinxian County was most, accounting for 36.2% (25/69); the sex ratio of men and women was 22 ∶ 1 (66 ∶ 3), and the age of the cases was mainly 20 - < 60 years old, accounting for 97.1% (67 cases); the occupation distribution was dominated by workers, accounting for 26.1% (18/69). The 69 malaria cases were all imported cases from abroad, of which 67 cases were imported from Africa, accounting for 97.1%.Conclusions:There is no report of local malaria case in Nanchang from 2016 to 2020, all cases are imported from abroad. In the future, the control and prevention of imported personnel from abroad should be strengthened.

Objective:To observe the clinical effect of four-point fixation in patients with posterior chamber intraocular lens dislocation.Methods:A retrospective case series study was adopted.Sixteen patients (16 eyes) with posterior chamber intraocular lens dislocation who underwent suture suspension techniques with four-point fixation in Changzhou No.2 people's Hospital from January 2015 to January 2018 were enrolled.Postoperative effects were observed during follow-up, ranging from 6 to 13 months.The preoperative and 6-month postoperative uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), corneal endothelium cell count and astigmatism were measured and the differences were compared, and the relationships between total astigmatism and corneal astigmatism or intraocular lens induced astigmatism were analyzed, and the postoperative position of intraocular lens and complications were observed.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Changzhou No.2 People's Hospital (No.2015-C-012-01).Written informed consent was obtained from each patient before surgery.Results:The mean preoperative UCVA (LogMAR) and BCVA (LogMAR) were 1.09±0.24 and 0.48±0.20, respectively, which were significantly improved to 0.30±0.12 and 0.26±0.13 at 6 months after operation, respectively.And the differences were statistically significant ( t=11.782, 3.795; both at P<0.01).The preoperative and 6-month postoperative corneal endothelium cell count were (2 270±360)/mm 2 and (2 032±327)/mm 2, respectively, and the difference was not significant ( t=1.921, P=0.074).The 6-month postoperative mean total astigmatism, corneal astigmatism and intraocular lens induced astigmatism were (-1.47±0.82)D, (-1.34±0.61)D and (-0.22±0.35)D, respectively.There was a highly positive correlation between total astigmatism and corneal astigmatism ( r=0.885, P<0.05), but there was no significant correlation between total astigmatism and intraocular lens induced astigmatism ( r=-0.432, P=0.095).No dislocation, deviation or torsion of intraocular lens were observed during the follow-up.Varying degree of symptoms of iridocyclitis were observed during early stage after operation, which disappeared after treatment.There were two cases of high intraocular pressure, which were normal after treatment.No retinal detachment, choroidal detachment, expulsive suprachoroidal hemorrhage, endophthalmitis, corneal endothelial decompensation or other complications occurred during and after operation. Conclusions:There is a stable position of intraocular lens, good visual acuity and few complications after four-point fixation with suture and suspension, which is a feasible method to treat dislocated intraocular lens.