1.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
2.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
3.The Oncogenic Role of TNFRSF12A in Colorectal Cancer and Pan-Cancer Bioinformatics Analysis
Chuyue WANG ; Yingying ZHAO ; You CHEN ; Ying SHI ; Zhiying YANG ; Weili WU ; Rui MA ; Bo WANG ; Yifeng SUN ; Ping YUAN
Cancer Research and Treatment 2025;57(1):212-228
Purpose:
Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms.
Materials and Methods:
Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A.
Results:
TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer.
Conclusion
TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.
4.Phase changes and quantity-quality transfer of raw material, calcined decoction pieces, and standard decoction of Ostreae Concha (Ostrea rivularis).
Hong-Yi ZHANG ; Jing-Wei ZHOU ; Jia-Wen LIU ; Wen-Bo FEI ; Shi-Ru HUANG ; Yu-Mei CHEN ; Chong-Yang LI ; Fei-Fei LI ; Qiao-Ling MA ; Fu WANG ; Yuan HU ; You-Ping LIU ; Shi-Lin CHEN ; Lin CHEN ; Hong-Ping CHEN
China Journal of Chinese Materia Medica 2025;50(5):1209-1223
The phase changes and quantity-quality transfer of 17 batches of Ostreae Concha(Ostrea rivularis) during the raw material-calcined decoction pieces-standard decoction process were analyzed. The content of calcium carbonate(CaCO_3), the main component, was determined by chemical titration, and the extract yield and transfer rate were calculated. The CaCO_3 content in the raw material, calcined decoction pieces, and standard decoction was 94.39%-98.80%, 95.03%-99.22%, and 84.58%-90.47%, respectively. The process of raw material to calcined decoction pieces showed the yield range of 96.85% to 98.55% and the CaCO_3 transfer rate range of 96.92% to 99.27%. The process of calcined decoction pieces to standard decoction showed the extract yield range of 2.86% to 5.48% and the CaCO_3 transfer rate range of 2.59% to 5.13%. The results of X-ray fluorescence(XRF) assay showed that the raw material, calcined decoction pieces, and standard decoction mainly contained Ca, Na, Mg, Si, Br, Cl, Al, Fe, Cr, Mn, and K. The chemometric results showed an increase in the relative content of Cr, Fe, and Si from raw material to calcined decoction pieces and an increase in the relative content of Mg, Al, Br, K, Cl, and Na from calcined decoction pieces to standard decoction. X-ray diffraction(XRD) was employed to establish XRD characteristic patterns of the raw material, calcined decoction pieces, and standard decoction. The XRD results showed that the main phase of all three was calcite, and no transformation of crystalline form or generation of new phase was observed. Fourier transform infrared spectroscopy(FTIR) was employed to establish the FTIR characteristic spectra of the raw material, calcined decoction pieces, and standard decoction. The FTIR results showed that the raw material had internal vibrations of O-H, C-H, C=O, C-O, and CO■ groups. Due to the loss of organic matter components after calcination, no information about the vibrations of C-H, C=O, and C-O groups was observed in the spectra of calcined decoction pieces and standard decoction. In summary, this study elucidated the quantity-quality transfer and phase changes in the raw material-calcined decoction pieces-standard decoction process by determining the CaCO_3 content, calculating the extract yield and transfer rate, and comparing the element changes, FTIR characteristic spectra, and XRD characteristic pattern. The results were reasonable and reliable, laying a foundation for the subsequent process research and quality control of the formula granules of calcined Ostreae Concha(O. rivularis Gould), and providing ideas and methods for the quality control of the whole process of raw material-decoction pieces-standard decoction-formula granules of Ostreae Concha and other testacean traditional Chinese medicine.
Drugs, Chinese Herbal/isolation & purification*
;
Calcium Carbonate/analysis*
;
Quality Control
5.Processing technology of calcined Magnetitum based on concept of QbD and its XRD characteristic spectra.
De-Wen ZENG ; Jing-Wei ZHOU ; Tian-Xing HE ; Yu-Mei CHEN ; Huan-Huan XU ; Jian FENG ; Yue YANG ; Xin CHEN ; Jia-Liang ZOU ; Lin CHEN ; Hong-Ping CHEN ; Shi-Lin CHEN ; Yuan HU ; You-Ping LIU
China Journal of Chinese Materia Medica 2025;50(9):2391-2403
Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods*
;
Drugs, Chinese Herbal/chemistry*
;
Quality Control
;
Particle Size
6.Early clinical outcomes of 3D-printed individualised customised prostheses in hip revision combined severe bone defect.
Hong-Ping WANG ; Ming-You WANG ; Xiao-Qin YANG ; Zhuo-Dong TANG ; Xun-Zhou SONG ; Yu-Ping LAN
China Journal of Orthopaedics and Traumatology 2025;38(2):163-169
OBJECTIVE:
To explore the early clinical outcomes of 3D printed individualised customised prostheses for in hip revision in patients with combined severe bone defects.
METHODS:
Twenty-two patients from January 2021 to May 2023 underwent hip revision using 3D printed personalised customised prostheses were retrospective analyzed, including 10 males and 12 females, age 28 to 78 with a mean of (58.9±12.8) years old. All of patients were combined with severe bone defects (Parprosky type Ⅲ). Among of them, 9 patients had periprosthetic infections and 13 patients had aseptic prosthesis loosening. All patients were treated with a 3D printed personalised prosthesis protocol, patients with the periprosthetic infection received a second stage revision after infection control. The operation time, preoperative waiting time, intraoperative and postoperative complications were recorded, and the clinical efficacy were evaluated at the final follow-up using the visual analogue scale (VAS) for pain, the Harris hip score.
RESULTS:
One patient was lost to follow-up and the remaining 21 patients were followed up for 10 to 15 with a mean of (12.91±1.44) months after surgery. All patients completed surgery as planned, with an operative time of 135 to 390 with a mean of (165.4±39.3) minutes and a preoperative waiting time of 7 to 16 with a mean of (10.5±3.3) days. Regarding patient complications:one patient had a severe intraoperative periprosthetic femoral fracture due to the combination of severe osteoporosis; one patient had an intraoperative greater trochanteric femur fracture. At the latest follow-up, all patients had good position of the custom-made prosthesis and no loosening of the prosthesis;all patients had good wound healing and no local redness or swelling. The total Harris score at the final follow-up (85.86±7.04) was significantly improved compared to the preoperative (44.86±2.36), P<0.001. The VAS at the last follow-up (2.19±0.87) was significantly improved compared with preoperative (7.41±0.96), P<0.001.
CONCLUSION
The clinical efficacy of 3D-printed personalised customised prosthesis in combined severe bone defect hip revision is satisfactory, but due to the increased preoperative waiting time of the patients and certain risks, certain indications should be mastered when applying in the clinic.
Humans
;
Male
;
Female
;
Printing, Three-Dimensional
;
Middle Aged
;
Aged
;
Adult
;
Retrospective Studies
;
Hip Prosthesis
;
Arthroplasty, Replacement, Hip
;
Reoperation
;
Prosthesis Design
;
Treatment Outcome
7.Efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases: A systematic review and meta-analysis.
Li YANG ; Bo FANG ; Can-Qin HE ; Xu-Xin ZHAN ; You-Ping XIAO ; Xiao-Jun QIN ; Qiang LOU ; Xue-Jun SHANG
National Journal of Andrology 2025;31(4):349-356
OBJECTIVE:
To evaluate the efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases.
METHODS:
Relevant studies were retrieved from PubMed, EMBASE, Cochrane, Web of Science, Sinomed , CNKI and Wanfang databases. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of included studies, and relevant data were extracted. meta-analysis was performed using RevMan 5.4 and RStudio software, and forest plots were generated.
RESULTS:
Six randomized controlled trials (RCTs) were included. Compared with the control group, denosumab significantly reduced the risk of skeletal-related events (HR=0.78, 95% CI: 0.62-0.93). In terms of safety, denosumab did not increase the risk of total adverse events, severe adverse events and the adverse events higher than CTC grade 3.
CONCLUSION
Denosumab can delay the time to first skeletal-related event with good safety. However, due to the limitations of this study, further high-quality, large-sample, multicenter RCTs are needed to confirm these findings.
Humans
;
Denosumab/therapeutic use*
;
Bone Neoplasms/drug therapy*
;
Prostatic Neoplasms/drug therapy*
;
Male
;
Randomized Controlled Trials as Topic
;
Bone Density Conservation Agents/therapeutic use*
8.Analysis of the causes of cage subsidence after oblique lateral lumbar interbody fusion
Zhong-You ZENG ; Ping-Quan CHEN ; Xing ZHAO ; Hong-Fei WU ; Jian-Qiao ZHANG ; Xiang-Qian FANG ; Yong-Xing SONG ; Wei YU ; Fei PEI ; Shun-Wu FAN ; Guo-Hao SONG ; Shi-Yang FAN
China Journal of Orthopaedics and Traumatology 2024;37(1):33-44
Objective To observe the cage subsidence after oblique lateral interbody fusion(OLIF)for lumbar spondylo-sis,summarize the characteristics of the cage subsidence,analyze causes,and propose preventive measures.Methods The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively ana-lyzed.There were 43 males and 101 females,and the age ranged from 20 to 81 years old,with an average of(60.90±10.06)years old.Disease types:17 patients of lumbar intervertebral disc degenerative disease,12 patients of giant lumbar disc hernia-tion,5 patients of discogenic low back pain,33 patients of lumbar spinal stenosis,26 patients of lumbar degenerative spondy-lolisthesis,28 patients of lumbar spondylolisthesis with spondylolisthesis,11 patients of adjacent vertebral disease after lumbar internal fixation,7 patients of primary spondylitis in the inflammatory outcome stage,and 5 patients of lumbar degenerative scoliosis.Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis,and 87 patients of normal bone density.The number of fusion segments:124 patients of single-segment,11 patients of two-seg-ment,8 patients of three-segment,four-segment 1 patient.There were 40 patients treated by stand-alone OLIF,and 104 patients by OLIF combined with posterior pedicle screw.Observed the occurrence of fusion cage settlement after operation,conducted monofactor analysis on possible risk factors,and observed the influence of fusion cage settlement on clinical results.Results All operations were successfully completed,the median operation time was 99 min,and the median intraoperative blood loss was 106 ml.Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients.The mean follow-up was(14.57±7.14)months from 6 to 30 months.During the follow-up,except for the patients of primary lumbar interstitial in-flammation and some patients of lumbar spondylolisthesis with spondylolisthesis,the others all had different degrees of cage subsidence.Cage subsidence classification:119 patients were normal subsidence,and 25 patients were abnormal subsidence(23 patients were grade Ⅰ,and 2 patients were grade Ⅱ).There was no loosening or rupture of the pedicle screw system.The height of the intervertebral space recovered from the preoperative average(9.48±1.84)mm to the postoperative average(12.65±2.03)mm,and the average(10.51±1.81)mm at the last follow-up.There were statistical differences between postop-erative and preoperative,and between the last follow-up and postoperative.The interbody fusion rate was 94.4%.The low back pain VAS decreased from the preoperative average(6.55±2.2 9)to the last follow-up(1.40±0.82),and there was statistically significant different.The leg pain VAS decreased from the preoperative average(4.72±1.49)to the final follow-up(0.60± 0.03),and the difference was statistically significant(t=9.13,P<0.000 1).The ODI index recovered from the preoperative av-erage(38.50±6.98)%to the latest follow-up(11.30±3.27)%,and there was statistically significant different.The complication rate was 31.3%(45/144),and the reoperation rate was 9.72%(14/144).Among them,8 patients were reoperated due to fusion cage subsidence or displacement,accounting for 57.14%(8/14)of reoperation.The fusion cage subsidence in this group had obvious characteristics.The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group,Stand-alone OLIF group,2 or more segments fusion group,and endplate injury group was higher than that in the normal bone mass group,OLIF combined with pedicle screw fixation group,single segment fusion group,and no endplate injury group,and the comparison had statistical differences.Conclusion Cage subsidence is a common phenomenon after 0-LIF surgery.Preoperative osteopenia or osteoporosis,Stand-alone OLIF,2 or more segments of fusion and intraoperative end-plate injury may be important factors for postoperative fusion cage subsidence.Although there is no significant correlation be-tween the degree of cage subsidence and clinical symptoms,there is a risk of cage migration,and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence,including reoperation.
9.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
10.Contrast-enhanced ultrasound for evaluating area of coagulation necrosis after microwave ablation of rabbit liver:Comparison with pathological findings
Ping HE ; Xia LUO ; Xin YANG ; Xiaoqing TANG ; You YANG ; Juying ZHNAG ; Yuanlin GAN ; Jinhong YU
Chinese Journal of Medical Imaging Technology 2024;40(10):1461-1465
Objective To observe area of coagulation necrosis after microwave ablation(MWA)of rabbit liver showed on contrast-enhanced ultrasound(CEUS)in comparison with pathological findings.Methods Twenty-five healthy male experimental rabbits were equally randomly divided into L0,M0,H0,M7 and M14 groups.MWA was achieved with different power and time,and then CEUS and pathological examinations were performed,respectively.Four target areas of rabbit liver were ablated under 20 W for 1 min in L0 group,under 30 W for 1 min in M0 group and under 30 W for 3 min in H0 group,and the ablated areas were observed on the same day after MWA,while 2 target areas of rabbit liver were ablated under 30 W for 1 min in M7 and M14 groups,and the ablated areas were observed 7 days and 14 days after MWA,respectively.The ablated foci and ablated foci+edema band(inflammatory reaction band,IRB)showed on CEUS and pathology were compared,and their differences and changes with time going were analyzed.Results On the day of ablation,the extent of ablation foci,ablation foci+IRB as well as IRB in L0,M0 and H0 groups showed on CEUS were all larger than pathological findings under light microscopy(all P<0.05),and the difference value of the length of the ablation foci between 2 methods increased sequentially among group L0,M0 and H0(all adjusted P<0.05).Seven days after ablation,the area of ablation foci measured with CEUS in M 7 group was slightly larger than that measured with pathology(adjusted P=0.045),but no significant difference of the length nor the short diameter was found(both adjusted P>0.05).Fourteen days after ablation,no significant difference of the length,the short diameter nor the area of ablation foci was detected between 2 methods in M14 group(all adjusted P>0.05).The length,short diameter and area of ablation foci in M0 group measured with CEUS or pathology were all smaller than those in M 7 and M14 groups(all adjusted P<0.05),while no significant difference was found between the latter 2 groups(all adjusted P>0.05).Conclusion On the day of MWA of rabbit liver with different power and time settings,the areas of ablation foci,ablation foci+IRB and IRB showed on CEUS were larger than pathological findings.The range of ablation foci showed on CEUS 7 days after ablation was basically in line with pathology,indicating that CUES should be reexamined 7 days after ablation to evaluate the actual extent of coagulation and necrosis of ablation foci.

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