1.Improvement of neutral protease activity of Bacillus amyloliquefaciens LX-6 by combined ribosome engineering and medium optimization and its application in soybean meal fermentation.
Yifan ZHU ; Xinyi HUANG ; Tao HAN ; Jiteng WANG ; Xiaoping YU ; Zheng MA
Journal of Zhejiang University. Science. B 2025;26(8):805-812
Soybean meal (SBM) prepared by soybean crushing is the most popular protein source in the poultry and livestock industries (Cai et al., 2015) due to its economic manufacture, high protein content, and good nutritional value. Despite these benefits, SBM contains various antigen proteins such as glycinin and β-conglycinin, which account for approximately 70% of the total proteins of the SBM and reduce digestibility and damage intestinal function (Peng et al., 2018). Treating SBM with proteases (neutrase, alcalase, and trypsin) or fermentation can eliminate these antigen proteins (Contesini et al., 2018). Because of its safety and rapid growth cycle, Bacillus strains are considered ideal for the fermentation industry (Yao et al., 2021). SBM fermented by Bacillus yields products with high nutritional value and low levels of antinutritional factors (ANFs), stimulating research in this area (Yuan et al., 2017). Kumari et al. (2023) demonstrated that fermentation with Bacillus species effectively degrades antigen proteins and increases crude protein content. The degradation of antigen proteins relies on protease hydrolysis. Low protease production is the major obstacle hindering the widespread use of microbial fermentation techniques.
Bacillus amyloliquefaciens/metabolism*
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Fermentation
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Glycine max/metabolism*
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Soybean Proteins/metabolism*
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Peptide Hydrolases/metabolism*
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Ribosomes/metabolism*
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Globulins
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Antigens, Plant
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Seed Storage Proteins
2.Identification of HMA gene family and response to cadmium stress in Ophiopogon japonicas.
Zhihui WANG ; Erli NIU ; Yuanliang GAO ; Qian ZHU ; Zihong YE ; Xiaoping YU ; Qian ZHAO ; Jun HUANG
Chinese Journal of Biotechnology 2025;41(2):771-790
Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]4P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism*
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Adenosine Triphosphatases/metabolism*
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Ophiopogon/drug effects*
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Soil Pollutants/toxicity*
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Plant Proteins/metabolism*
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Stress, Physiological
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Multigene Family
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Gene Expression Regulation, Plant
3.Research Progress on the Application of Large Language Model-based Intelligent Medical Assistants
Yuchen ZHANG ; Chuantao WANG ; Hailiang XIA ; Jiliang ZHAI
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1511-1518
Large language models (LLMs), represented by ChatGPT, have garnered significant attention due to their powerful capabilities in understanding and generating human language. Research on the application of LLMs across various medical tasks has shown a vigorous development trend. This review aims to outline the development and clinical applications of LLMs, with a focus on the primary tasks of medical intelligent assistants, including their associated opportunities and challenges. At the technical level, we provide a detailed explanation of the architecture and training processes of existing medical LLMs, and summarize the general technical steps for adapting large models to the healthcare domain. At the application level, we introduce the main tasks of medical intelligent assistants from both healthcare provider- and patient-oriented perspectives, andcompare the performance of different LLMs across various medical tasks to illustrate their unique advantages and limitations in medical applications.
4.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850,封3
177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.
5.National bloodstream infection bacterial resistance surveillance report(2022): Gram-positive bacteria
Chaoqun YING ; Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(2):99-112
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units,and the top five bacteria were Staphylococcus aureus( n=1 147,36.3%),coagulase-negative Staphylococci( n=928,29.3%), Enterococcus faecalis( n=369,11.7%), Enterococcus faecium( n=296,9.4%)and alpha-hemolyticus Streptococci( n=192,6.1%). The detection rates of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)were 26.4%(303/1 147)and 66.7%(619/928),respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome,rifampin,compound sulfamethoxazole,linezolid,minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%(2/369),and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions( χ2=14.578, P=0.002),while the detection rate of MRCNS in northern China was significantly higher than that in other regions( χ2=15.195, P=0.002). The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals( χ2=13.519 and 12.136, P<0.001). The detection rates of MRSA and MRCNS in economically more advanced regions(per capita GDP≥92 059 Yuan in 2022)were higher than those in economically less advanced regions(per capita GDP<92 059 Yuan)( χ2=9.969 and 7.606, P=0.002和0.006). Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China, Staphylococci is the most common while the MRSA incidence decreases continuously with time;the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China,with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.
6.Application study of test bolus and high-flow rate injection scheme in thyroid CT enhancement
Gaoxue LIN ; Yan ZHOU ; Jianwei WANG ; Jiliang CHEN ; Xiaoquan XU ; Lulu XU
Journal of Practical Radiology 2024;40(8):1349-1353
Objective To explore the application value of test bolus combined with a high-flow rate injection scheme in improving the quality of thyroid CT enhancement images.Methods A total of 126 patients who underwent thyroid plain scan and enhanced CT were selected.Among them,63 underwent conventional examination methods(control group),while the remaining 63 patients received test bolus and high-flow rate injection scheme(experimental group).Objective evaluation included the signal-to-noise ratio(SNR),contrast-to-noise ratio(CNR),thyroid enhancement rate,thyroid parenchyma-cancer difference,artifact index(AI)of the two groups of arterial phase images,thyroid enhancement rate of the two groups of venous phase images,and contrast agent dose of the two groups were all compared.Statistical analysis was performed via independent sample t-test or Mann-Whitney U test.Subjective evaluation included the evaluation of thyroid display in two groups of arterial phase images was conducted via the 4-point method,followed by the implementation of the Mann-Whitney U test.Results The SNR,CNR,thyroid enhancement rate,thyroid parenchyma-cancer difference,and AI in the arterial phase images of the experimental group were all significantly superior to those of the control group(P<0.05).There was no statistically significant difference in the thyroid enhancement rate in the venous phase between control group and experimental group(P>0.05);The contrast agent dose of the experimental group was significantly lower than that of the control group(P<0.01).The thyroid display score observed in the arterial phase images of the experimental group was significantly higher than that of the control group(P<0.01).Conclusion Using a test bolus combined with a high-flow rate injection scheme can significantly improve the image quality of thyroid CT enhancement.
7.Application of three-dimensional simulated osteotomy of the distal femur in total knee arthroplasty
Tihui WANG ; Xu WANG ; Jinqing WU ; Jiliang CHEN ; Xiaolu WANG ; Juan MIAO
Chinese Journal of Tissue Engineering Research 2024;28(6):905-910
BACKGROUND:Studies have shown that there are significant differences in the geometric morphology of the distal femur of different races and genders,and there are more short female patients in southern China,so the phenomenon of overhanging or insufficient coverage of imported knee prostheses often occurs during surgery. OBJECTIVE:To investigate the characteristics of distal femur bones in southern Chinese women and compare them with imported joint prostheses by simulating the three-dimensional reconstruction of the distal femur bone and matching the femoral side after osteotomy with common imported joint prostheses. METHODS:From January to December 2021,120 female volunteers underwent a CT scan of knee joints.The images were imported into Mimics 20.0 software in Dicom format for three-dimensional reconstruction and then imported into Magic 22.0 software to simulate osteotomy by posterior cruciate ligament preserved total knee arthroplasty and to conduct a matching study with a normal imported joint prosthesis. RESULTS AND CONCLUSION:(1)The functional anteroposterior dimension(fAP)of the distal femur and Persona matched prosthesis had a total overhang rate of 25%(30/120).The fAP≤47 mm group had an overhang than the other groups(P<0.05).The poor coverage rate of Triathlon prosthesis was 12.5%(15/120),and poor coverage was more likely in fAP>53 mm group than in fAP≤53 mm group(P<0.05).(2)The total poor coverage rate of femoral intercondylar width matching with Triathlon prosthesis was 27.5%(33/120).Therefore,the poor coverage rate of bone surface in the central region of the distal femur was more likely in the fAP≤47 mm group than in other groups(P<0.05).The overhang rate of Journey II was 21.6%(26/120),and the overhang rate was higher in the fAP>53 mm group than in the fAP≤53 mm group(P<0.05).(3)Journey II CR prosthesis had the largest difference with the length of the anterior mediolateral diameter of the femur,which was easy to hang out on the anterolateral side of the femoral prosthesis.The Persona CR prosthesis has the largest difference with the length of the posterior mediolateral diameter of the femur,which is easy to be poorly covered in the posterior medial part of the prosthesis.It is recommended to increase the femoral prosthesis with reduced mediolateral diameter in the fAP≤47 mm group and add wider and narrower sizes than the conventional size of intercondylar width,and optimize the anterolateral angular arc design of the femoral prosthesis to improve the matching of posterior cruciate ligament reserved knee prosthesis.
8.Moderate and severe valgus knee by total knee arthroplasty through medial and lateral parapatellar approach
Tihui WANG ; Xu WANG ; Jinqing WU ; Jiliang CHEN ; Qijin WANG ; Hongwei XU ; Jianguo LIN
Chinese Journal of Tissue Engineering Research 2024;28(30):4825-4830
BACKGROUND:Prosthesis restricted selection,soft tissue release,patellar trajectory recovery,and bone defect reconstruction were need to be optimized in total knee arthroplasty for moderate and severe valgus knee.The medial parapatellar approach has disadvantages in the treatment of valgus knee,such as aggravating the medial soft tissue relaxation.In recent years,it has been found that the lateral parapatellar approach has advantages in the treatment of valgus knee,such as exposure and release. OBJECTIVE:To observe the efficacy of the lateral and medial parapatellar approach in total knee arthroplasty for moderate and severe valgus knee,and to explore a more suitable surgical approach for moderate and severe valgus knee. METHODS:Totally 56 patients with moderate and severe valgus knee underwent total knee arthroplasty and would take turns performing surgery through the medial and lateral parapatellar approach according to the order of admission.The lateral group(n=28)underwent total knee arthroplasty through lateral parapatellar approach,and the medial group(n=28)through medial parapatellar approach.Posterior stablized knee prosthesis was used in all patients.The restricted types of prosthesis,thickness of polyethylene,operation time,amount of blood loss,femoro-tibia angle,patellar tilt angle,range of motion,Hospital for Special Surgery score,Western Ontario and McMaster Universities Arthritis Index(WOMAC)score,and complications were collected as observation indexes for statistical analysis. RESULTS AND CONCLUSION:(1)The utilization rate of condyle-restricted prosthesis in the lateral group was significantly lower than that in the medial group.The average thickness of polyethylene liner was lower,and the operation time was shorter in the lateral group compared with the medial group.There were significant differences between the two groups(P<0.05),and there was no significant difference in the amount of surgical bleeding.(2)56 patients were followed up for an average of 2-5 years.There were no signs of prosthesis loosening or bone resorption in all patients.The average patellar tilt angle and femoral tibial angle of the lateral group were lower than those of the medial group,and the average Hospital for Special Surgery score and WOMAC score of the lateral group were higher than those of the medial group,with significant differences(P<0.05).There was no significant difference in the range of motion of the knees between the two groups.(3)Incision fat liquefaction and calf intermuscular venous thrombosis occurred in one case in each group.No infection,poor incision healing,incisional hematoma,prosthesis dislocation,iatrogenic nerve injury,ectopic ossification,or periprosthesis fracture occurred during follow-up.(4)In conclusion,the treatment of moderate and severe valgus knee by lateral parapatellar approach can better protect the tension of the medial soft tissue of the knee,use less condylar restrictive prostheses,and have a more friendly patellar trajectory and higher postoperative function score.
9.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
10.Current status of diagnosis and management of postoperative complications after endoscopic endonasal transsphenoidal approach to pituitary adenoma removal
Guangmou CAI ; Hao WANG ; Jiliang HU
Clinical Medicine of China 2023;39(2):134-139
Pituitary adenoma is one of the most common intracranial tumors, and most of them can be well removed by endoscopic transsphenoidal surgery. Pituitary adenoma is located in the sella, which can compress the pituitary and optic nerve, invade the sphenoid sinus and cavernous sinus, invade and grow in all directions, and affect the endocrine function at the same time. Endoscopic transsphenoidal pituitary adenoma resection (EETS) has the advantages of minimally invasive, close observation, panoramic view, high tumor resection rate and high preservation rate of normal pituitary function, but it can cause pituitary endocrine disorder, diabetes insipidus, electrolyte disorder, cerebrospinal fluid leakage, intracranial infection, cerebral nerve paralysis, tumor cavity, intracranial hemorrhage, rhinitis and other related complications. It affects the prognosis and quality of life of patients. The postoperative complications of EETS are not only related to the pathophysiological characteristics of pituitary adenoma, but also closely related to the depth of understanding of pathology and anatomy of pituitary adenoma, surgical skills, proficiency and clinical experience. Familiarity with endoscopic anatomy and fine surgical techniques, rich surgical experience, strict preoperative endocrine function evaluation, hormone replacement therapy, etc. can reduce the incidence of postoperative complications of EETS.

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