1.Global burden of thyroid cancer in 2022: Incidence and mortality estimates from GLOBOCAN
Zhangyan LYU ; Yu ZHANG ; Chao SHENG ; Yubei HUANG ; Qiang ZHANG ; Kexin CHEN
Chinese Medical Journal 2024;137(21):2567-2576
Background::Thyroid cancer (TC) is the most common malignancy of the endocrine system. This study aimed to assess the global distribution of TC incidence and mortality in 2022, as well as to predict the burden for the year 2050.Methods::Data from the GLOBOCAN 2022 database were used to analyze the age-standardized incidence and mortality rates of TC by sex, age group (<55 years and ≥55 years), country, world region, and level of Human Development Index (HDI) for 185 countries. The predicted incidence and mortality burden for 2050 was calculated based on demographic projections.Results::In 2022, an estimated 821,214 new TC cases and 47,507 TC-related deaths occurred worldwide. The age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were higher in women (ASIR: 13.60 per 100,000; ASMR: 0.53 per 100,000) than in men (ASIR: 4.60 per 100,000; ASMR: 0.35 per 100,000). The ASIR in high HDI countries was approximately ten times higher than that in low HDI countries for both sexes, with relatively similar ASMR across regions. Among 185 countries, China had the largest number of TC cases (accounting for 56.77% of total cases) and TC-related deaths (accounting for 24.35% of global TC-related deaths), with the highest ASIR in men (13.30 per 100,000). Worldwide, approximately 64.63% of TC cases occurred in populations under 55 years old, while nearly 82.99% of TC-related deaths occurred in populations aged 55 years and above. If the rates stay the same as in 2022, it is projected that approximately 1,100,000 new TC cases and 91,000 TC-related deaths will occur in 2050, indicating a 34.15% and 89.58% increase, respectively.Conclusions::TC is a highly frequent cancer worldwide with disparities across regions, genders, and age groups. Our results provide light on the worldwide TC disease burden and facilitate regionally customized prevention measures.
2.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
3.On-line Measurement of Styrene Secondary Organic Aerosol Using Synchrotron Radiation Vacuum Ultraviolet Photoionization Aerosol Mass Spectrometer
Ming-Qiang HUANG ; Xiao-Bin SHAN ; Liu-Si SHENG ; Zhen-Ya WANG ; Chang-Jin HU ; Xue-Jun GU ; Wei-Jun ZHANG
Chinese Journal of Analytical Chemistry 2024;52(8):1200-1210
Secondary organic aerosol(SOA)produced by photooxidation of styrene and other aromatic compounds is a major part of fine particles in urban atmosphere.In this study,the measurement of component and content of SOA formed from photooxidation of styrene in smog chamber using synchronous radiation vacuum-ultraviolet photoionization aerosol mass spectrometer(VUV-PIAMS)was conducted.Photoionization mass spectra of styrene SOA was detected by synchrotron radiation photon with 10.5 eV,and the proportion of main components was quantified based on the peak area of each ion peak.The photoionization efficiency curve of ion peak was obtained under synchrotron radiation photons in the range from 7.5 to 11.5 eV,and then the ionization potential was acquired for qualitative analysis of the component structure.The results showed that the photoionization mass spectra of styrene SOA mainly contained ion peaks at m/z 106,108,120 and 122,and the ionization potentials of each peak were(9.41±0.03)eV,(8.93±0.03)eV,(9.24±0.03)eV and(9.25±0.03)eV,respectively.Combined with quantum chemistry calculation and off-line measurement verification of infrared absorption spectra and electrospray ionization mass spectra,it was determined that benzaldehyde,benzyl alcohol,4-vinylphenol and benzoic acid were main components of styrene SOA,accounting for 32.5%,17.5%,25%and 15%of the measured components,respectively,and the generated quantity ratio was 13∶7∶10∶6.VUV-PIAMS could overcome the disadvantages of off-line method,and could on-line detect component and content of SOA,proving a useful tool to measure the chemical components and reveal the formation process of SOA particles.
4.Advances in research of dual inhibitors targeting Janus kinase and histone deacetylase
Jing SHEN ; Wei-jie HU ; Guo-qiang DONG ; Chun-quan SHENG ; Ya-hui HUANG
Acta Pharmaceutica Sinica 2024;59(11):3057-3073
Janus kinase (JAK) and histone deacetylase (HDAC) referred to as crucial targets in autoimmune diseases and cancers have achieved quite success in the treatment of these diseases. Until now, several JAK and HDAC inhibitors have been approved. Recently, developing single multi-targeting inhibitors including JAK/HDAC dual inhibitors based on network pharmacology has made significant progress in improving therapeutic efficacy, reducing toxic and side effects, and overcoming drug resistance. In this review, we summarize novel JAK/HDAC dual inhibitors as well as JAK/HDAC-based triple-targeting inhibitors, in order to provide reference for the discovery of novel JAK/HDAC dual inhibitor.
5.Prone position lateral lumbar interbody fusion combined with posterior pedicle screw fixation for the treatment of lumbar degenerative diseases
Yonghui ZHAO ; Sheng LU ; Qiang YANG ; Weichao LI ; Jiayu CHEN ; Qiyang WANG ; Tiannan ZOU ; Kun HUANG ; Jie LIU ; Hui ZHONG
Chinese Journal of Orthopaedics 2024;44(17):1151-1158
Objective:To explore the feasibility and clinical efficacy of prone transpsoas lateral interbody fusion (PTP LIF) combined with posterior pedicle screw fixation for the treatment of lumbar degenerative diseases in the prone position.Methods:A total of 23 patients who underwent LLIF in the prone position at the First People's Hospital of Yunnan Province between March 2023 and October 2023 were retrospectively analyzed. The cohort comprised 9 males and 14 females, with a mean age of 55.5±8.8 years (range, 41-70 years). The clinical diagnoses included intervertebral disc herniation with endplate inflammation (3 cases), lumbar spinal stenosis (13 cases), lumbar spondylolisthesis (5 cases), and lumbar instability (2 cases). The surgical segments involved L 3, 4 (15 cases), L 4, 5 (6 cases), and L 3-L 5 (2 cases), with 21 cases involving a single segment and 2 cases involving double segments. The disc height and lumbar lordosis Angle before and after surgery were compared. Lower back pain was evaluated using the visual analogue scale (VAS), while lumbar spine function was assessed via the Oswestry Disability Index (ODI). Clinical efficacy was evaluated according to the modified MacNab criteria at the last follow-up. Results:All surgeries were successfully completed. The operation time was 120.2±21.4 min (range, 90-175 min), intraoperative blood loss was 131.1±40.8 ml (range, 60-200 ml), and the hospital stay was 6.2±1.6 days (range, 4-10 days). Follow-up was obtained for all 23 cases, with the follow-up time being 9.6±2.2 months (range, 6-13 months). One case of endplate damage occurred during surgery, two cases of transient psoas muscle weakness occurred postoperatively, and one case of lower limb pain and numbness was reported; no cases of wound infection or delayed healing were observed. The postoperative disc height improved compared to preoperative (6.8±1.9 mm; F=66.618, P<0.001). There was no statistically significant difference between 3 months postoperative (11.1±1.2 mm) and immediately postoperative (12.2±1.2 mm; P>0.05), but there was a statistically significant difference between the last follow-up (10.7±1.1 mm) and immediately postoperative ( P<0.05). The postoperative lumbar lordosis angle improved compared to preoperative (35.3°±5.4°; F=19.465, P<0.001), with no statistically significant difference between 3 months postoperative (44.1°±5.4°) and immediately postoperative (47.8°±6.6°; P>0.05), but there was a statistically significant difference between the last follow-up (43.2°±5.3°) and immediately postoperative ( P<0.05). The postoperative VAS score improved compared to preoperative (6.3±1.1 points; F=79.931, P<0.001), and the last follow-up (1.1±1.1 points) showed further improvement compared to 3 months postoperative (1.7±1.4 points; P<0.05). The postoperative ODI improved compared to preoperative (69.9%±7.4%; F=592.392, P<0.001), with 3 months postoperative (23.1%±3.1%) showing improvement compared to 1 month postoperative (29.2%±3.1%), and the last follow-up (17.5%±3.6%) showing further improvement compared to 3 months postoperative ( P<0.05). At the last follow-up, the modified MacNab criteria were: excellent in 16 cases, good in 5, fair in 2, with an excellent and good rate of 91% (21/23); 7 cases of cage subsidence were observed, with no cases of internal fixation loosening. Conclusion:PTP LIF combined with pedicle screw fixation for the treatment of lumbar degenerative diseases is safe and effective, with satisfactory short-term postoperative outcomes.
6.A single-center study on the distribution and antibiotic resistance of pathogens causing bloodstream infection in patients with hematological malignancies.
Lin Jing CAI ; Xiao Lei WEI ; Yong Qiang WEI ; Xu Tao GUO ; Xue Jie JIANG ; Yu ZHANG ; Guo pan YU ; Min DAI ; Jie Yu YE ; Hong Sheng ZHOU ; Dan XU ; Fen HUANG ; Zhi Ping FAN ; Na XU ; Peng Cheng SHI ; Li XUAN ; Ru FENG ; Xiao Li LIU ; Jing SUN ; Qi Fa LIU
Chinese Journal of Hematology 2023;44(6):479-483
Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.
Humans
;
Bacteremia/epidemiology*
;
Cefoperazone
;
Sulbactam
;
Retrospective Studies
;
Drug Resistance, Bacterial
;
Microbial Sensitivity Tests
;
Hematologic Neoplasms
;
Sepsis
;
Anti-Bacterial Agents/pharmacology*
;
Gram-Negative Bacteria
;
Gram-Positive Bacteria
;
Piperacillin, Tazobactam Drug Combination
;
Escherichia coli
7.Analysis of transmission dynamics and effectiveness of control of local epidemics caused by the Omicron BA.2 and BA.5.2 COVID-19 strains in Fujian Province
Wen-Jing YE ; Sheng-Gen WU ; Mei-Rong ZHAN ; Zheng-Qiang HUANG ; Shao-Jian CAI ; Wu CHEN ; Jian-Ming OU ; Jie-Feng HUANG ; Tian-Mu CHEN ; Yan-Qin DENG ; Kui-Cheng ZHENG
Chinese Journal of Zoonoses 2023;39(11):1065-1071
This study evaluated the scientific nature and effectiveness of iterative optimization of prevention and control measures for local outbreaks caused by the BA.2 and BA.5.2 COVID-19 strains in Fujian Province in 2022,to provide a scientif-ic basis for responding to future new or recurrent respiratory infectious diseases.According to the theory of infectious disease dynamics,relevant information regarding the local epidemic situation caused by the BA.2 sub-type Omicron virus strain in March 2022 and BA.5.2 sub-type Omicron virus strain in October 2022 in Fujian Province was collected.The susceptible exposed infectious removed(SEIAR)model of COVID-19 infection with a latent period and asymptomatic infected persons was used to analyze the transmission dynam-ics of two local epidemic situations,and evaluate the preven-tion and control effects.The incubation period of the BA.2 epidemic was 3 days(1~9 days),the intergenerational inter-val was 3 days(1~5 days),and the initial Rt was 3.0(95%CI:2.7~3.3).The incubation period of the BA.5.2 epidemic was 2 days(1~6 days),the intergenerational interval was 1 day(0~2 days),and the initial R,was 1.9(95%CI:1.7~2.1).The fittingresults for the BA.2 and BA.5.2 epidemics were good,and no statistical difference was observed between the predic-ted and actual numbers of cases(x2BA.2=31.53,x2BA.5.2=27.88,P>0.05).If an emergency response had not been initiated,the BA.2 epidemic would have continued to spread andpeak on April 7th,with an estimated 638 035 cases.The BA.5.2 epidemic would have rapidly spread,reaching a peak on November 14th,with an estimated 685 940 cases.If one incubation period were detected early,the scale of the BA.2 epidemic would have decreased by 25.73%;if two incubation periods were detected early,the scale would have decreased by 79.56%,and if one incubation period had been delayed,the scale would have expanded by 13.72%.If one incubation period had been detected early in the BA.5.2 epidemic,the scale would have decreased by 35.04%;if two incubation periods had been detected early,the scale would have decreased by 92.47%;and if one incubation period had been delayed,the scale would have increased by 19.75%.The guiding ideology,and the prevention and control measures for handling two local epidemics were optimized and iterated.Our study indicated that implementing the"four early"measures ef-fectively decreased the scale of the epidemic,and earlier detection was associated with more significant control effects.This study provides valuable information for the prevention and control of new or recurrent respiratory infectious diseases.
8.Comparison of efficacy of different doses of Conbercept combined with panretinal photocoagulation and EX-PRESS glaucoma shunt implantation in the treatment of neovascular glaucoma
Su-E ZHONG ; Sheng HUANG ; Mang-Qian RAO ; Wen-Qiang ZHANG
International Eye Science 2022;22(12):2058-2062
AIM: To evaluate the efficacy and safety of three doses of Conbercept intravitreal injection with panretinal photocoagulation(PRP)followed by EX-PRESS glaucoma shunt implantation on patients with neovascular glaucoma(NVG).METHODS: Prospective study. A total of 37 patients(37 eyes)with NVG from May 2018 to September 2020 were collected. All accepted intravitreal injection of Conbercept and PRP 3-5d later, and accepted EX-PRESS glaucoma shunt implantation within 1wk after surgery. They were randomly divided into the low-dose group(13 eyes), the conventional dose group(12 eyes)and the high-dose group(12 eyes)according to three doses of preoperative Conbercept intravitreal injection, and they were injected with 10mg/mL Conbercept of 0.03, 0.05 and 0.08 mL(0.3, 0.5 and 0.8 mg Conbercept contained)respectively. The regression of iris and angle neovascularization(NV)after intravitreal injection was observed in the three groups, and postoperative intraocular pressure(IOP), best corrected visual acuity(BCVA)and complications were compared among the three groups.RESULTS: All patients completed follow-up. Cases with NV regression of iris and angle in the high-dose group were significantly more than the low-dose group(χ2=0.132, P=0.003)and the conventional dose group(χ2=0.154, P=0.015)3-5d after intravitreal injection. BCVA and IOP of the three groups at 1, 3 and 6mo after surgery were improved compared with those before treatment. IOP of the low-dose group, the conventional dose group and the high-dose group at 12mo after surgery was 14.12±2.63, 13.37±2.18 and 12.15±1.43mmHg, respectively. IOP of the high-dose group was lower than that of the low-dose group and the conventional dose group(all P<0.05). The BCVA of the high-dose group at 12mo after surgery was better than that of the low-dose group and the conventional dose group(all P<0.05). There was no significantly statistical difference in the incidence of postoperative complications at 12mo after surgery among the three groups(P>0.05).CONCLUSIONS: The intravitreal injection of high-dose(0.8mg)Conbercept combined with PRP and EX-PRESS glaucoma shunt implantation has particularly significant clinical effect on the treatment of NVG.
9.Data Mining Study on Prescription Patterns of Different Dosage Forms of Chinese Herbal Medicines for Treating and Improving Immune-Inflammatory Indices in Patients with Rheumatoid Arthritis.
Dan HUANG ; Jian LIU ; Ling XIN ; Jin-Gui XIE ; Qiang ZHU ; Pei-Sheng CHEN ; Zhi-Bin SHEN ; Qing-He MENG ; Hai-Yan WANG
Chinese journal of integrative medicine 2022;28(3):215-222
OBJECTIVE:
To explore the prescription patterns of different dosage forms of Chinese herbal medicines (CHMs) for the treatment of rheumatoid arthritis (RA) and their effects on immune-inflammatory indices.
METHODS:
Clinical data were collected from patients with RA in 4 hospitals (3 Class A comprehensive hospitals and 1 Class B comprehensive hospital) in Anhui Province, China, from August 2012 to June 2018 via the electronic medical record gathering system. Following extraction of prescription information, each prescribed herb was quantified and standardized according to the knowledge base to establish a database of RA treatment formulae. The medical records were divided into the granules group and decoction pieces group. Core herbs and their combination patterns were obtained from the two groups of cases using Liquorice software. Changes in immune-inflammatory and hepatic and renal function indices were compared between the two groups using SPSS 23.0 software. The Aprior module of SPSS Clementine 11.1 software was applied to analyse the correlation between CHMs and improvement in indices. Finally, the ORACLE 10 g tool was used to evaluate the random walk model of the immune-inflammatory indices between the two groups.
RESULTS:
(1) We retrospectively analysed 35,898 prescriptions for 6,829 patients with RA who received CHM treatment. There were 3,816 patients in the granules group and 3,013 in the decoction pieces group. (2) The core herbs were Pi (Spleen)-strengthening and dampness-resolving drugs, blood-activating and stasis-resolving drugs, wind/dampness-dispelling drugs and heat-clearing and detoxifying drugs. (3) Both dosage forms could improve immune-inflammatory indices in RA patients, with similar efficacy and no influence on hepatic or renal function. (4) Herba Siegesbeckiae and Oldenlandia had a stronger association with immune-inflammatory indices in the two groups. (5) The immune-inflammatory indices showed obvious improvement after treatment with granules and decoction pieces of CHMs, and there were long range correlations between the comprehensive evaluation indices and interventions.
CONCLUSIONS
The principal CHM treatment methods for RA in four hospitals in Anhui Province are strengthening Pi and resolving dampness, activating blood and resolving stasis, dispelling wind/dampness and clearing heat. Granules and decoction pieces of CHMs have similar efficacy in improving immune-inflammatory indices in RA patients and could be used as treatment options for RA.
Arthritis, Rheumatoid/drug therapy*
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Data Mining
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Drugs, Chinese Herbal/therapeutic use*
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Humans
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Medicine, Chinese Traditional
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Prescriptions
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Retrospective Studies
10.Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Cognitive Function in Senior Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Randomized Controlled Trial.
Hua WEI ; Jun-Sheng HUANG ; Fang ZHAO ; Zhi-Qiang XIE ; Zhi-Yang XIA ; Jian-Hui GAN
Chinese journal of integrative medicine 2022;28(8):730-735
OBJECTIVE:
To evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) for improving postoperative cognitive function in senior patients undergoing video-assisted thoracoscopic surgical (VATS).
METHODS:
From January to December 2020, 97 participants were randomly assigned to the TEAS group (49 cases) and the control group (48 cases) by a random number table. The patients in the TEAS group received TEAS, at the bilateral Neiguan (PC 6) and Zusanli (ST 36) acupoints. The control group received sham TEAS. The stimulation was started from 30 min before surgery until the end of the operation. The primary outcome was the incidence of pstoperative cognitive dysfunction (POCD), diagnosed based on the changes in the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. The secondary outcomes were plasma levels of S100β protein and neuron-specific enolase (NSE).
RESULTS:
The incidence of POCD on day 1 and 3 after surgery in the TEAS group was significantly lower than that in the control group [day 1 after surgery: 28.3% (13/46) vs. 52.3% (23/44), P=0.028; day 3 after surgery: 21.7% (10/46) vs. 40.9% (18/44), P=0.043]. Compared with baseline, the MMSE and MoCA scores decreased to various extents in both groups. The MMSE scores on day 1, 3, and 5 after surgery and MoCA scores on day 1, 3, 5, and 7 after surgery in the TEAS group were higher than those in the control group (all P<0.05) in both groups. Compared with baseline, the plasma levels of S100β and NSE were significantly increased at 4, 8, 12, 24 h after surgery (all P<0.05). Compared with the control group, the plasma levels of S100β and NSE were lower in the TEAS group at 4, 8, 12, and 24 h after surgery (all P<0.05). No obvious adverse events were found during the trial.
CONCLUSION
Application of TEAS in senior patients after VATS could reduce incidence of POCD and improve postoperative cognitive function.
Acupuncture Points
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Cognition
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Humans
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Postoperative Period
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Thoracic Surgery, Video-Assisted/adverse effects*
;
Transcutaneous Electric Nerve Stimulation

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