1.Value of serum Aldo-keto reductase family 1 member B10 (AKR1B10) in diagnosis of hepatocellular carcinoma
Yunling DU ; Changjiang SHI ; Fangyuan GAO ; Mengna ZHANG ; Lingling WANG ; Zhuqing ZHANG ; Ying MING ; Shoujun XIE
Journal of Clinical Hepatology 2025;41(4):684-689
ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 (AKR1B10) in patients with hepatocellular carcinoma (HCC) in northern China, and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC, 119 patients with benign liver disease, and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein (AFP). The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve (AUC) was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 (1 475.67 — 4 605.86) pg/mL in the HCC group, 1 324.42 (659.68 — 2 023.88) pg/mL in the benign liver disease group, 660.68 (377.56 — 2 087.77) pg/mL in the other malignant tumor group, and 318.30 (82.73 — 478.82) pg/mL in the healthy group, with a significant difference between the four groups (H=240.86, P<0.001), and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups (all P<0.001). The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC, with an AUC of 0.86 (95% confidence interval [CI]: 0.82 — 0.90), a sensitivity of 74.3%, and a specificity of 85.2%. Compared with each indicator alone, a combination of AKR1B10 and AFP could improve the sensitivity (81.8%) and specificity (91.4%) of HCC diagnosis. AKR1B10 had an AUC of 0.84 (95%CI: 0.78 — 0.90) in the diagnosis of patients with early- or middle-stage HCC, with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 (95%CI: 0.77 — 0.92) in the diagnosis of patients with AFP-negative HCC, with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC, and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China, especially those with early- or middle-stage HCC and AFP-negative HCC.
2.Preoperative prediction of GPC3 positive hepatocellular carcinoma and postoperative recurrence with the LI-RADS features on gadoxetate disodium-enhanced MRI
Ning ZHANG ; Minghui WU ; Changjiang YU ; Yiran ZHOU ; Cong WANG ; Dandan SHI ; Shaocheng ZHU
Chinese Journal of Radiology 2024;58(1):64-70
Objective:To investigate the predictive ability of Glypican-3 (GPC3) positive hepatocellular carcinoma based on the hepatobiliary specific contrast agent gadoxetate disodium enhancement of the liver imaging reporting and data system version 2018 (LI-RADS v2018) imaging features, and to assess the relevant clinical imaging features for postoperative recurrence in GPC3 positive HCC patients.Methods:This study was a cohort study. A total of 122 hepatocellular carcinoma patients who underwent gadoxetate disodium enhanced MRI examination with hepatic tumor resection in Henan Provincial People′s Hospital from January 2017 to December 2021 were retrospectively collected, including 96 GPC3 positive and 26 GPC3 negative patients. The imaging features defined by LI-RADS v2018 of HCC lesions were analyzed. Patients were followed up for 40 months to determine recurrence free survival (RFS). The logistic regression was used to analyze the risk factors of GPC3 positivity. An imaging model, and a clinical-imaging model which combined the patient′s alpha-fetoprotein levels were constructed. The efficacy of the model for predicting GPC3 positivity was assessed using receiver operating characteristic curves. Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the RFS between GPC3 positive and negative patients. Risk factors affecting the recurrence of GPC3 positive HCC were assessed by Cox regression.Results:The results of logistic multivariate regression analysis confirmed that rim enhancement ( OR=5.685, 95% CI 1.229-26.287, P=0.026) and irregular tumor margin at hepatobiliary phase ( OR=4.431, 95% CI 1.684-11.663, P=0.003) were independent risk factors for GPC3 positive HCC. The area under the curve for predicting GPC3 positivity was 0.745 (95% CI 0.636-0.854) for the imaging model and 0.776 (95% CI 0.677-0.876) for the clinical-imaging model. The mean RFS in the GPC3 positive group was 22 months, and it was 32 months in the negative group. There was a statistically significant difference in RFS between the two groups ( χ2=5.15, P=0.023). The multivariate Cox regression analysis showed that the arterial rim enhancement ( HR=5.460, 95% CI 1.966-15.162, P=0.001), microvascular invasion ( HR=2.402, 95% CI 1.210-4.769, P=0.012), portal vein tumor thrombus ( HR=3.226, 95% CI 1.114-9.344, P=0.031) were independent risk factors for recurrence after hepatic tumor resection for GPC3-positive HCC. Conclusions:A model based on the LI-RADS v2018 imaging features of hepatobiliary specific contrast agent gadoxetate disodium enhancement can effectively predict GPC3 positive HCC. The arterial rim enhancement, microvascular invasion and portal vein tumor thrombus are independent risk factors for postoperative recurrence of GPC3 positive HCC.
3.Establishment of a LASSO-Logistic Regression-based Risk Prediction Model for Early Recurrence of Siewert Ⅱ/Ⅲ Adenocarcinoma of Esophagogastric Junction Post-Surgery
Zuyu ZHANG ; Hong WEI ; Qian LIU ; Yaoqiang WANG ; Xueyan FAN ; Ruiying LUO ; Changjiang LUO
Medical Journal of Peking Union Medical College Hospital 2024;15(3):604-615
To investigate the risk factors for early relapse after curative resection of Siewert type Ⅱ/Ⅲ adenocarcinoma of esophagogastric junction (AEG) and construct a visual predictive model. A retrospective analysis was conducted on the clinicopathological data of patients diagnosed with Siewert type Ⅱ/Ⅲ AEG who underwent curative resection at the Second Hospital of Lanzhou University from January 2016 to March 2021. The samples were randomly divided into a training group and a validation group in a 7∶3 ratio. The LASSO-Logistic regression method was used to select variables predictive of early recurrence of Siewert type Ⅱ/Ⅲ AEG and construct a predictive model for early recurrence. The model was validated through 1000 bootstrap resampling. Receiver operating characteristic (ROC) curves were drawn, and area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to evaluate the model's stability. According to the inclusion and exclusion criteria of this study, a total of 320 Siewert type Ⅱ/Ⅲ AEG patients were included, with 122 experiencing recurrence within two years. LASSO-Logistic regression analysis revealed AJCC staging, degree of differentiation, CA199, CEA, NLR, and tumor maximum diameter as independent predictive factors for early recurrence of Siewert type Ⅱ/Ⅲ AEG. A predictive model was constructed with these factors and depicted as a nomogram. For the training group, the AUC of the ROC curve was 0.836(95% CI: 0.785-0.887), with a sensitivity of 81.4% and a specificity of 85.6%;for the validation group, the AUC was 0.812(95% CI: 0.711-0.912), with a sensitivity of 80.6% and a specificity of 87.7%. Calibration curves for both the training and validation groups displayed curves close to the reference line, indicating high model stability. The DCA curve showed that the model provided a good net benefit with threshold probabilities between 0.05 and 0.75. A multivariate model developed using LASSO-Logistic regression could predict early relapse in patients with Siewert type Ⅱ/Ⅲ AEG, which may be instrumental in assessing patient prognoses and in guiding postoperative surveillance and management for patients with Siewert type Ⅱ/Ⅲ AEG.
4.GNMT inhibits intrauterine adhesion fibrosis through TGF-β1/Smad3 signaling pathway and its mechanism
Hong GU ; Jia WANG ; Wenwen ZHANG ; Xiao YANG ; Xiyue HUANG ; Yingfeng ZHANG ; Yanhua MAO ; Changjiang LI ; Qiuhong CHEN ; Jinglin HUANG ; Qi LIU ; Ling WEI ; Congcong SUN
Journal of Army Medical University 2024;46(18):2110-2120
Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6~8 weeks old and weighing from 180~220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.
5.Application of radium-223 combined with new-generation hormonal agents in bone metastatic of prostate cancer
Haozhong HOU ; Changjiang YU ; Penghe QUAN ; Xiaozheng FAN ; Longlong ZHANG ; Zhe WANG ; Xiaojian YANG
Chinese Journal of Urology 2023;44(5):325-329
Objective:To investigate the efficacy and safety of radium-223 in combination with new-generation hormonal agents in patients with bone metastases of prostate cancer.Methods:The clinical data of 17 patients (12 from the First Affiliated Hospital of Airforce Military Medical University and 5 from Xi'an International Medical Center Hospital) with metastatic castration-resistant prostate cancer(mCRPC) treated by radium-223 combined with new-generation hormonal agents from January 2021 to June 2022 were retrospectively analyzed. In all cases, the average age was (73.3±8.5) years old. Before treatment, the median prostate-specific antigen (PSA) was 15.7 (3.2, 36.5) ng/ml, the median alkaline phosphatase (ALP) was 131.5 (79.0, 430.7) U/L. All patients had ≥ 2 bone metastases but no visceral or lymph node metastases. The median number of bone scan lesions was 10(8, 15). Bone pain symptom was present in 16(94.1%) patients. There were 9 cases (52.9%) with Eastern Cooperative Oncology Group (ECOG) score of ≥2, 1 case (5.9%) with ECOG score of 1 and 6 cases (35.2%) with ECOG score of 0. All patients were treated with radium-223 (55 kBq/kg, injected every 4 weeks for a maximum of 6 cycles), of which 5 patients were combined with enzalutamide, 8 patients combined with apatamide and 4 patients combined with bicalutamide. PSA response (PSA decreased by ≥30% from baseline and maintained for at least 1 month), ALP response (ALP decreased by ≥30% from baseline and maintained for at least 1 month) and pain relief rates were analyzed. Imaging evaluation was performed before and after treatment to calculate the objective response rate of metastases. The incidence of treatment-related adverse effects and skeletal related event (SRE) were also recorded.Results:Eleven patients completed 6 courses, 3 patients completed 5 courses and 3 patients completed ≥4 courses. The median ALP after 1 month of last treatment was 83.2 (51.5, 126.5) U/L, which was significantly decreased than baseline. 12 patients (70.6%) showed an ALP response and the other 5 (29.4%) showed varying degrees of ALP elevation. PSA response was observed in 4 patients (23.5%), of which 2 (11.8%) had a continuous decrease and 2 (11.8%) had a late-stage increase in PSA. Pain relief was relieved in 15 cases (88.2%) during treatment, 1 case (5.9%) had worsening pain due to disease progression and 1 case (5.9%) had no change during treatment. The ECOG score decreased in 15 (88.2%) patients. The median number of bone metastases in patients decreased to 5 (4, 9). One patient (5.9%) had complete remission during treatment, 11 patients (64.7%) had a partial response, 4 patients (23.5%) were stable, and 1 (5.9%) showed imaging progression after 4 months of treatment. The overall objective remission response rate was 70.5% (12/17). Treatment-related hematologic adverse effects included anemia (1 case, 5.9%, grade 3), thrombocytopenia (1 case, 5.9%, grade 3) and leukopenia (1 case, 5.9%, grade 2). Non-hematologic adverse effects included fatigue (3 cases, 17.6%, 2 cases in grade 1, 1 case in grade 2), gastrointestinal bleeding (1 case, 5.9%, grade 3), diarrhea (1 case, 5.9%, grade 2) and fever (1 case, 5.9%, grade 1). Patients with grades 1 to 2 relieved with symptomatic management. Three cases (17.6%) were discontinued due to intolerance of grade 3 adverse reactions and 1 case (5.9%) terminated on its own. There was no SRE during treatment and follow-up.Conclusions:Radium-223 combined with New-generation hormonal agents has a high objective remission rate in patients with mCRPC, which could provide pain relief and improve quality of life. The incidence of adverse reactions was low and well tolerated.
6.Study on the relationship between habitat factors and the distribution
Yitian GAO ; Fan GAO ; Da XYU ; Fengyang MIN ; Jiasheng WANG ; Yi YUAN ; Kongxian ZHU ; Xiaoguang LIU ; Yunchao ZHANG
Journal of Public Health and Preventive Medicine 2022;33(3):22-27
Objective To explore the relationship between the distribution characteristics and the habitat factors of the invasive B. straminea in South China. Methods From October 2016 to August 2017, the breeding condition and habitat factors of B. straminea were investigated in the rivers of Shenzhen and its adjacent areas in the dry season, normal season and wet reason. The generalized additive model (GAM) was used to study the main habitat factors affecting the distribution density of B. straminea. Results The distribution characteristics of B. straminea showed obvious aggregation and unevenness in space. In terms of time, the density of snails was the highest in the dry season, followed by the normal water season and the least in the wet season. The GAM model analysis showed that the main habitat factors affecting the distribution density of B. straminea were water depth, water temperature, flow velocity, dissolved oxygen, and total phosphorus. When the flow velocity and water temperature were 0.25 m / s and 26 °C, respectively, the largest distribution density of snails might appear. The distribution density of B. straminea was positively correlated with dissolved oxygen and total phosphorus. Conclusion B. straminea is suitable to live in the water environment with poor water quality. In the future, the monitoring should be strengthened to provide reference for the prevention and control of the spread of the snails.
7.Study on the different extraction fractions of Agrimonia pilosa against hepatic fibrosis
Lin LI ; Chunyan RAO ; Qingsong LEI ; Yi HUANG ; Huabao LIU ; Changjiang ZHANG
China Pharmacy 2022;33(3):313-318
OBJECTIVE To study different extraction fractions of Agrimonia pilosa against h epatic fibrosis. METHODS Using hepatic stellate cells HSC-T 6 of rats as objects ,the effects of different extraction fractions (total extract ,ethyl acetate fraction , petroleum ether fraction and n-butanol fraction )with different concentrations (0.5,5,50,500,5 000 μg/mL,calculated by raw drug)of A. pilosa on the proliferation of HSC-T 6 cells were detected (after treated for 24,48,72 h);median inhibition concentration(IC50)was also caculated. Platelet-derived growth factor (PDGF-BB)was used to induce the activation of HSC-T 6 cells to establish hepatic fibrosis cell model. Flow cytometry was used to detect the effects of different extraction fractions of A. pilosa on apoptosis of HSC-T 6 cells. The expression of collagen Ⅰ(Col-Ⅰ)in the supernatant was detected by enzyme linked immunosorbent assay. The expressions of α-smooth muscle actin (α-SMA),Col-Ⅰ,B-cell lymphoma- 2(Bcl-2),Bcl-2-associated X protein (Bax)and caspase- 3 were detected by Western blot assay. RESULTS Total extract ,ethyl acetate fraction ,petroleum ether fraction and n-butanol fraction of A. pilosa could significantly increase the apoptotic rate of HSC-T 6 cells(P<0.01). After treated for 24 h,IC50 of above fractions were 50.17,20.75,5.82,4.09 μg/mL,respectively. After intervened with PDGF-BB ,the expression of Col- Ⅰ in supernatant of HSC-T 6 cells as well as protein expression of Col- Ⅰ,α-SMA,Bcl-2,Bax and caspase- 3 in HSC-T6 cells were increased significantly (P<0.01). After intervened with different extraction fractions of A. pilosa ,most of the expressions of above proteins in HSC-T 6 cell culture supernatant or cells were significantly reversed compared with PDGF-BB group (P<0.05 or P<0.01), and the intervention effect of n-butanol fraction of A. pilosa was the most significant. CONCLUSIONS Different extraction fractions of A. pilosa can inhibite the proliferation of HSC-T 6 cells and induce their apoptosis;n-butanol fraction from A. pilosa may be an effective fraction to exert the effect of anti-hepatic fibrosis.
8.Finite element analysis of the effect of knee movable unicompartmental prosthesis insertion shape and mounting position on stress distribution in the knee joint after replacement.
Mingxin ZHAO ; Yuan GUO ; Changjiang WANG ; Xushu ZHANG ; Binping JI ; Kai ZHANG ; Dongdong HE
Journal of Biomedical Engineering 2022;39(4):660-671
In unicompartmental replacement surgery, there are a wide variety of commercially available unicompartmental prostheses, and the consistency of the contact surface between the common liner and the femoral prosthesis could impact the stress distribution in the knee after replacement in different ways. Medial tibial plateau fracture and liner dislocation are two common forms of failure after unicompartmental replacement. One of the reasons is the mismatch in the mounting position of the unicompartmental prosthesis in the knee joint, which may lead to failure. Therefore, this paper focuses on the influence of the shape of the contact surface between the liner and the femoral prosthesis and the mounting position of the unicompartmental prosthesis on the stress distribution in the knee joint after replacement. Firstly, a finite element model of the normal human knee joint was established, and the validity of the model was verified by both stress and displacement. Secondly, two different shapes of padded knee prosthesis models (type A and type B) were developed to simulate and analyze the stress distribution in the knee joint under single-leg stance with five internal or external rotation mounting positions of the two pads. The results showed that under a 1 kN axial load, the peak contact pressure of the liner, the peak ACL equivalent force, and the peak contact pressure of the lateral meniscus were smaller for type A than for type B. The liner displacement, peak contact pressure of the liner, peak tibial equivalent force, and peak ACL equivalent force were the smallest for type A at 3° of internal rotation in all five internal or external rotation mounting positions. For unicompartmental replacement, it is recommended that the choice of type A or type B liner for prosthetic internal rotation up to 6° should be combined with other factors of the patient for comprehensive analysis. In conclusion, the results of this paper may reduce the risk of liner dislocation and medial tibial plateau fracture after unicompartmental replacement, providing a biomechanical reference for unicompartmental prosthesis design.
Arthroplasty, Replacement, Knee/methods*
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Biomechanical Phenomena
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Finite Element Analysis
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Humans
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Knee Joint/surgery*
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Knee Prosthesis
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Tibia/surgery*
9.Survival outcomes of patients with intrahepatic cholangiocarcinoma undergoing surgical resection
Ruolin WU ; Changjiang ZHANG ; Enqiang GUO ; Guanghou CHEN ; Songbing LIU ; Hongyu WU ; Xiaojun YU ; Fan HUANG ; Guobin WANG ; Hongchuan ZHAO ; Xiaoping GENG
Chinese Journal of General Surgery 2022;37(12):896-902
Objective:To investigate the clinical outcomes of patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection.Methods:Patients who undergoing radical surgical resection for ICC from Jan 2015 to Apr 2021 at the Department of General Surgery, the First Affiliated Hospital of Anhui Medical University were included in this retrospective cohort study.Results:There were 67 patients in the final analysis, The median follow-up duration was 14 months (range: 1-60 months). Firty three patients (79.1%) had tumor recurrence, 52 patients (77.6%) died, Among them, 49 patients (73.1%) died from tumor recurrence. The 1-、2-、and 3-year accumulated disease-free and overall survival rate were 35.6%, 19.6%, 16.8% and 53.7%, 32.4%, 20.8%. respectively. The overall survival rate of the group without microvascular invasion was significantly better than those of the group with microvascular invasion ( χ2=5.916, P=0.015). CA19-9≥1 000 U/ml was the only independent risk factor for the disease-free survival. CA19-9≥1 000 U/ml、blood loss≥600 ml、microvascular invasion and tumor recurrence were the independent risk factors for the overall survival. Conclusion:For ICC patients with single tumor, when the tumor diameter is less than 5 cm and has no microvascular invasion, surgical resection is recommended, and a satisfactory prognosis could be achieved.
10.Application experience of ventricular intracranial pressure monitoring in the treatment of traumatic multiple intracranial hematoma
Dongyuan LIU ; Hao WANG ; Ziming HOU ; Jun YANG ; Changjiang WANG ; Hongbing ZHANG
Chinese Journal of Postgraduates of Medicine 2022;45(7):639-642
Objective:To investigate the significance of ventricular intracranial pressure monitoring in the treatment of traumatic multiple intracranial hematoma (TMIH).Methods:The clinical data of 14 TMIH patients treated with ventricular intracranial pressure monitoring from January 2016 to August 2021 in Beijing Luhe Hospital, Capital Medical University were analyzed retrospectively. The patients were followed up 6 months after injury, and the Glasgow outcome score (GOS) was assessed.Results:All the 14 patients successfully completed ventricular intracranial pressure probe placement. Among them, 8 patients recovered well after continuous monitoring of ventricular intracranial pressure and continuous cerebrospinal fluid drainage. Their ventricular intracranial pressure probe was placed for 5 to 10 (7.3 ± 2.2) d, with no intracranial infection occurred; and their GOS was 5 scores 6-month follow-up after injury. Six cases underwent craniotomy for hematoma removal due to the expansion of intracranial hematoma or aggravation of edema, and decompressive craniectomy was performed during the operation; 6-month follow-up after injury, GOS of 5 scores was in 3 cases, 4 scores in 2 cases, 3 scores in 1 case.Conclusions:The condition of TMIH patients is complex and changeable, and ventricular intracranial pressure monitoring can improve the prognosis of TMIH patients.


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