OBJECTIVES: To investigate the role of the calcium/calmodulin (CaM)-mediated activation of calcineurin (CN)-nuclear factor of activated T cells (NFAT) signaling pathway in mediating the regulatory effect of hyperforin (HY) on stress-induced depression-like disorder (DP) in mice. METHODS: C57BL/6J mice were randomly divided into control group, DP model group, and hyperforin treatment group (n=15). Behavioral changes of the mice were assessed using open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), light/dark box test (LDB), and novel object suppression test (NSFT). Immunohistochemistry was used to detect tyrosine hydroxylase (TH) expression in the CA1 region of the hippocampus, and serum serotonin (5-HT) and norepinephrine (NA) levels were detected with ELISA. Western blotting was used to analyze the expressions of TNF-α, IL-1β, IL-2, and CN-NFAT pathway proteins. In cultured BV-2 microglial cells with lipopolysaccharide (LPS) stimulation, the effects of hyperforin and CN inhibitor (CNIS) on expressions of ionized calcium-binding adapter molecule 1 (IBA-1), 5-HT, NA, inflammatory cytokines and CN-NFAT pathway proteins were examined using immunofluorescence assay, ELISA or Western blotting. RESULTS: Compared with the control mice, the mice in DP group showed significantly reduced activity in OFT, decreased sucrose consumption in SPT, reduced shuttle crossing in LDB, and lowered food intake in NSFT with significantly increased immobility in TST. The mice with DP showed significantly decreased TH-positive neurons, lowered 5-HT and NA levels, and increased expressions of TNF-α, IL-1β, IL-2 and CaM-CN-NFAT pathway proteins. In cultured BV-2 cells, LPS stimulation strongly increased cellular IBA-1 expression, decreased the levels of neurotransmitters (5-HT and NA), and increased the levels of inflammatory cytokines and CN-NFAT signaling, and these changes were effectively reversed by treatment with hyperforin or CNIS. CONCLUSIONS Hyperforin improves stress-induced depression-like behaviors in mice and activated BV-2 cells by targeting the CN-NFAT signaling pathway.
Animals ; Mice, Inbred C57BL ; Mice ; Microglia/drug effects* ; Depression/etiology* ; Perylene/pharmacology* ; Calcineurin/metabolism* ; NFATC Transcription Factors/metabolism* ; Calcium Signaling/drug effects* ; Stress, Psychological ; Phloroglucinol/pharmacology* ; Signal Transduction ; Male ; Behavior, Animal/drug effects* ; Terpenes

Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Objective:To investigate the effects of different doses of oxiracetam (ORC) on the neurological impairment and oxidative stress ability of lead(Pb)-exposed rats.Methods:Total 32 male SD rats with SPF grade were randomly divided into control group, the lead-exposed group, low-dose ORC intervention group and high-dose ORC intervention group according to the random number table method, with 8 rats in each group.The neurobehavioral indexes of rats were measured by gait score, tail flicking test, hindlimb support test and Morris water maze test.The lead content in hippocampal tissue was detected by spectrophotometry.The cell morphology of hippocampal tissue was observed by HE staining.Superoxide dismutase (superoxide dismutase, SOD) level in hippocampal tissues was detected by xanthine oxidase, and the level of malondialdehyde (MDA) in the hippocampus tissue was detected by the thiobarbiturate, and the level of glutathione peroxidase (GPx) in the hippocampus tissue was detected by chemical colorimetric.SPSS 24.0 software was used for statistical analysis, one-way ANOVA was used for multiple group comparisons and LSD- t test was used for further pairwise comparisons. Results:(1)After 8 weeks of lead exposure, there was no significant difference in body weight among the 4 groups( F=0.869, P=0.469). (2)Results of neurobehavioral indicators: there were statistically significant differences in gait scores, tail flick time, hind limb deployment distance, escape latency, and number of crossing platforms among the four groups of rats ( F=7.854, 13.630, 8.484, 23.485, 45.457, all P<0.05). The gait score, tail flick time, hind limb deployment distance, and escape latency of the lead-exposed group rats were higher than those of the control group (all P<0.05), while the number of crossing platforms was lower than that of the control group ( P<0.05). The gait score, tail flick time, hind limb deployment distance, and escape latency of the high-dose ORC intervention group were lower than those of the lead exposed group (all P<0.05), and the number of crossing platforms was higher than that of the lead exposed group ( P<0.05). (3)Lead content in hippocampal tissue: there was a statistically significant difference in lead content in the hippocampus of the four groups( F=309.013, P<0.001). The lead contents of lead exposed group ((1.21±0.10)μg/g), low-dose ORC intervention group ((1.03±0.10)μg/g) and high-dose ORC intervention group ((1.02±0.06)μg/g) were higher than that of the control group((0.02±0.00) μg/g) (all P<0.05), while the lead content in the low-dose ORC intervention group and high-dose ORC intervention group were both lower than that of the lead exposed group (both P<0.05). (4) HE staining showed that compared with the control group, the hippocampal tissue cells in the lead exposed group were arranged disordered, the tissue was loose, and the number of cells was reduced.Compared with the lead exposed group, the hippocampal histiocytes were closely arranged and regular, and the nuclei were fuller.(5)Oxidative stress levels in hippocampal tissue: there were significant differences in MDA, GPx content and SOD activity of hippocampal tissues in the four groups( F=69.879, 56.757, 11.644, all P<0.001). The levels of SOD ((2.03±0.18)U/mg, (3.42±0.26)U/mg), GPx((67.29±7.94)nmol/mg, (89.50±7.94)nmol/mg) in the hippocampus tissue of the lead exposed group were lower than those of the control group (all P<0.05), while the content of MDA was higher than that of the control group((43.73±3.74) nmol/mg, (16.42±1.60) nmol/mg)( P<0.05). The levels of SOD ((3.32±0.12) U/mg) and GPx ((84.11±6.26) nmol/mg) in the high-dose ORC intervention group were higher than those in the lead exposed group (both P<0.05), while the levels of MDA ((21.05±2.56) nmol/mg) was lower than that in the lead exposed group ( P<0.05). Conclusion:ORC can alleviate neurological damage in rats caused by lead exposure, which may be related to the up-regulation of antioxidant capacity of hippocampal tissues, thereby improving pathological damage.

Objective:To analyze the trend of disease burden of rheumatoid arthritis in China from 1990 to 2019, and to provide scientific basis for formulating targeted prevention and treatment strategies of rheumatoid arthritis.Methods:Based on data of the global burden of disease study 2019 (GBD 2019), according to the number of people with the disease, the prevalence, incidence, disability adjusted life year (DALY) and DALY rate of RA were used to describe the disease burden of RA in China and the world from 1990 to 2019. Joinpoint model was used to analyze the average annual percentage change (AAPC) of age-standardized prevalence rate, age-standardized incidence rate and age-standardized DALY rate of RA in China and the world from 1990 to 2019. The trend of disease burden of RA was analyzed.Results:In general, the standardized prevalence of RA in China and the world showed an upward trend from 1990 to 2019, and the age-standardized prevalence of RA in China increased by 0.18% per year on average ( t=7.34 , P=0.025). The global average annual increase was 0.27%, with a statistically significant difference ( t=6.64, P=0.013). From 1990 to 2019, the standardized incidence rate in China showed an average annual increase of 0.08%( t=7.54, P=0.032), while the standardized incidence rate in the world showed an average annual decrease of 0.37% ( t= -5.64, P=0.001). In 2019, the number of patients and prevalence of RA in China were 4.309.4 million and 302.98/100 000, respectively. The number of new cases and incidence of RA were 22.25 million and 15.64/100 000, respectively. Compared with 1990, in 2019, the number of patients and prevalence rate increased by 114.17% and 78.23%, the number of new cases and incidence rate increased by 77.90% and 48.05%, and DALY rate increased by 109.05% and 73.97%, respectively. From 1990 to 2019, the prevalence rate, incidence rate and DALY rate of women were higher than those of men. Both the prevalence rate and DALY rate showed an increasing trend with age, with the highest in the age group of 75 years old and above. Conclusion:From 1990 to 2019, the standardized incidence rate of RA in China has more increase than that in the world, and the overall incidence and prevalence of RA in China are on the rise. The prevalence, incidence and DALY of RA varies among different populations in China. Women and middle-aged and elderly people are at high risk.

Objective:To explore the clinical effect of a self-designed wound measurement grid on the design of lobulated perforator flap.Methods:From January 2019 to December 2022, soft tissue defects in limbs of 9 patients were reconstructed by lobulated perforator flaps in the Department of Orthopaedics and Traumatology of Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine. The patients were 7 males and 2 females aged 21-55 years old with 40.3 years old in average. There were 6 upper limb defects and 3 lower limb defects. Self-designed wound measuring grids were applied to guide the design and excision of lobulated perforator flaps during surgery. Five patients were treated by lobulated perforator flap pedicled with the descending branch of lateral circumflex femoral artery and 4 by perforator flaps pedicled with dorsal interosseous artery. The areas of soft tissue defect were 4.0 cm×1.5 cm-26.0 cm×8.0 cm, and the sizes of the flaps were 4.5 cm×1.8 cm-22.0 cm×10.0 cm. After surgery, the blood supply of flaps, flap survival and wound healing were monitored. Flap survival, donor site recovery and limb function were observed at outpatient clinic over the postoperative follow-up, and the limb function was evaluated by the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association and Lower Extremity Measure(LEM).Results:In this study, a total of 17 of 18 lobes of the lobulated perforator flaps survived after surgery. One flap had venous occlusion and after exploration and further treatment, a necrosis occurred in 1 lobe of the lobulated flap and then a free flap transfer was performed again. All the wounds achieved stage-I healing. Postoperative follow-up lasted for 3-18 months with 8.6 months in average. All flaps had good colour and texture, satisfactory appearance and only linear scars remained in the donor sites, without pain and scar contracture. The reconstructed upper extremity defect were evaluated according to the Evaluation Standard of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, with 4 patients were in excellent and 2 in good. The reconstructed lower extremity defects were evaluated according to the LEM, and 2 patients were in excellent and 1 in good.Conclusion:The self-designed wound measurement grid was successfully applied in the design of lobed perforator flaps. It can accurately measure a wound surface and quickly extract a wound profile, and it is more convenient and intuitive to guide the design of flaps. It has a good effect in clinical application and further clinical trials are required.

Objective:To investigate the application of self-designed wound measuring grid in the measurement of wound and the design of perforator flap.Methods:From February 2018 to February 2020, 31 cases of soft tissue defects of limbs were repaired by free transfer of perforator flap. During the operation, the self-designed membrane with measurement grid was used to measure the wound surface. The flaps were designed and harvested according to the accurate measurement of the wound. The flaps were reviewed at hospital clinic during follow-up.Results:All patients entered 3-15 months of follow-up with an average of 8 months. All 31 flaps survived, of which 2 flaps encountered vascular crisis and were rescued after surgical exploration. There was no infection of flaps and all flaps had stage I healing. The flaps were satisfactory in appearance with the sensation recovery to S 2 in 21 cases and S 3 in 10 cases. Only linear scars were left on the donor sites. Conclusion:The membrane with a measurement grid can accurately measure a wound, and help the design of the flap according to the measured size and profile of the wound. It can reduce the operation time and the risk as well as to improve the operation efficiency. The clinical application is satisfactory. Large scale and multi-centre studies are required to further prove the benefit of the measurement grid.

Objective:To analysis effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy (combined screening strategy) for screenin the imported patients with COVID-19 in Xiamen.Methods:The study populations were overseas travelers arriving in Xiamen from March 17 to December 31, 2020, and overseas travelers who had quarantine outside Xiamen for less than 21 days from July 18 to December 31, 2020. Data were collected and analyzed on the timing of detection, pathways, and test results of the imported patients with COVID-19 after implementing combined screening strategy.Results:A total of 304 imported patients with COVID-19 were found from 174 628 overseas travelers and 943 overseas travelers from other cities. A total of 163 cases (53.6%) were diagnosed by multitime, multisite intensive nucleic acid testing after positive finding in total antibody testing. Among them, 27 (8.9%) were first positive for nucleic acid in 14 plus 7 day quarantine and 136 were first positive for nucleic acid in 14-day quarantine. Only 8 of these individuals were tested positive for nucleic acid after positive total antibody testing. The other 128 individuals were tested positive for nucleic acid after being negative for average 2.3 times (maximum of 6 times). Aditional 155 cases might be detected by using the combined "14 plus 7 day quarantine" and " nucleic acid plus total antibody testing" strategy compared with "14-day quarantine and nucleic acid testing" strategy, accounting for 51.0% of the total inbound infections. So the combined screening strategy doubled the detection rate for imported patients with COVID-19. No second-generation case caused by overseas travelers had been reported in Xiamen as of February 26, 2021.Conclusions:Xiamen's combined screening strategy can effectively screen the imported patients with COVID-19 who were first positive for nucleic acid after 14 day quarantine. Compared with "14 day quarantine and nucleic acid testing", the combined screening strategy improved detection rate and further reduced the risk of the secondary transmission caused by the imported patients with COVID-19.

Objective:To explore the clinical effect of the second toenail flap with the dorsal bone of the phalange in repairing the defect of fingernail bed.Methods:From January, 2012 to June, 2019, 10 patients with large area of fingernail bed defect were treated by the second toenail flap with bone on the back of the phalanx. The survival of the flap was observed after the operation, and the fracture healing, the shape of the nail and the flexion and extension function of the finger joint were observed in the outpatient follow-up.Results:All flaps of the second toenail survived. The average follow-up period was 8 (4-12) months. The fractured ends of 10 patients' phalanges healed well without nonunion, good appearance of toenail and deformity of toenail. The recovery of hand function was evaluated according to the evaluation standard of upper limb function of Hand Surgery Society of Chinese Medical Association, 9 cases were excellent, and 1 case was good.Conclusion:The second toenail flap with dorsal bone of the phalanx preserved is easy to cut, simple to operate, and has good clinical effect. It is a good method to repair the defect of the fingernail bed.

【Objective】 To investigate the diagnostic value of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) specific antibodies IgM and IgG on coronavirus disease 2019 (COVID-19). 【Methods】 1) The test results of SARS-CoV-2 IgM/IgG antibodies and nucleic acid(NAT), which were tested by colloidal gold test and fluorescent quantitative PCR respectively, were collected from 145 febrile outpatients during early March, 2020, named Fever group, in which retrospective analysis and paired chi-square test were performed. 2) 612 cases of SARS-CoV-2 IgM/IgG antibodies test results, which were done on March 5, 2020, were collected. They were named COVID-19 group (Our hospital was provisionally assigned as a specialized hospital for COVID-19, and 1500 COVID-19 patients admitted to our hospital from February 12, 2020 to March 18, 2020). The SARS-CoV-2 IgM/IgG antibodies and NAT were respectively tested on the 30th and the 60th day after the date of discharge. The clinical application values of the antibodies was clarified by statistical analysis. 【Results】 1) In the fever group, the positive rate of SARS-CoV-2 IgM, IgG and IgM+ IgG antibodies were 26.21% (38/145), 54.48% (79/145) and 26.21% (38/145), respectively(P<0.01), and the positive rate of NAT was 4.14% (6/145), which was lower than that of antibody (P<0.01). One (1/145, 0.69%) positive NAT was implicated in initially negative IgM and IgG antibodies samples. 2) In the COVID-19 group, the positive rate of IgM antibody was low (5%) and IgG antibody was high (65%) during 2~14 days after infection, and stably increased during the 15~56 days [IgM 47.68%(277/581) vs IgG 94.15% (547/581) ], then both decreased after 57 days. The positive rates of IgM antibody and IgG antibody were 45.8% (280/612) and 93.1% (570/612) in 612 patients during hospitalization. 15 patients′ data after dischange were not collected as they were later transferred to Huoshenshan Hospital for treatment. The coronavirus NAT results of the rest 597 COVID-19 patients, tested on the 30th and 60th days after the date of discharge, were negative, and the positive rates of IgG antibody and IgM antibody were still ≥80% and ≥40% respectively at the second month after discharge. 【Conclusion】 IgM, IgG antibody against SARS-CoV-2 can be well detected by Colloidal gold method(Innovita), whose positive rate is higher than that of NAT. IgG antibody is produced earlier than IgM, and it keeps high positive rate and persists for a long time. The combination of colloidal gold antibody test and NAT can improve the diagnose rate of COVID-19 and the exclusion of suspected cases.

Objective:To investigate the surgical method and clinical effect in the repair of thumb tip defect with radial thenar fasciocutaneous flap.Methods:From March, 2016 to January, 2019, 15 patients with thumb tip defect were treated by radial thenar fasciocutaneous flap. There were 6 defects in left thumb and 9 in right thumb. All the thumbtip defects had the exposure of digital bone, and some had defects of digital bone itself. The size of defects ranged from 1.0 cm×2.0 cm to 1.5 cm×3.0 cm, and the size of the flaps ranged from 1.2 cm×2.5 cm to 1.8 cm×4.0 cm. All of the donor sites were directly closed. The patients entered follow-up by outpatient visit, telephone calls or WeChat reviews to evaluate the quality of the flaps and the clinical effects of the surgery.Results:All flaps survived with good quality. All the donor sites achieved primary healing. The follow-ups lasted for 6 to 18 months with an average of 10.5 months. At the final follow-up review, the appearance of flaps was satisfactory in natural colour, flexible and wear-resistant. There were various degrees of sensation recovery of the flaps, with TPD from 6 mm to 12 mm. The sensation around the donor site was close to normal. Function of the thumbs was evaluated according to the total active movement (TAM) evaluation system. Twelve thumbs were graded excellent and 3 in good.Conclusion:The radial thenar fasciocutaneous flap achieved satisfactory clinical effect in the repair of thumb tip defect. The texture of the flaps is close to the recipient site and the damage to the donor site is minimal.