Effect of 5-aminolevulinic acid photodynamic therapy versus loop electrosurgical excision procedure for cervical intraepithelial neoplasia grade 2 treatment.

BACKGROUND: Both the traditional loop electrosurgical excision procedure (LEEP) and the newly developed 5-aminolevulinic acid photodynamic therapy (ALA-PDT) are used to treat high-grade squamous intraepithelial lesions. However, the clinical efficacy and safety of these two therapies have rarely been compared. Thus, this study aimed to compare the clinical efficacy and safety of the two treatment regimens. METHODS: One hundred and twenty patients in two groups (60 + 60) with grade 2 cervical intraepithelial neoplasia (CIN2) were voluntary treated with photodynamic therapy or LEEP between June 2020 and December 2022. Follow-up was conducted at 3, 4-6, and 7-12 months after treatment. RESULTS: Although the total effective rate of LEEP was higher during the first 6 months after treatment, both the total effective rate of lesion degradation and the double-negative rate of high-risk HPV16/18 and liquid-based cervical cytology by ALA-PDT treatment increased with time and finally exceeded those of LEEP at 7-12 months. CONCLUSIONS: ALA-PDT may be more promising than LEEP for treating patients with CIN2 because of the better CIN2 degradation and high-risk HPV negativity, less damage, and greater fertility conservation, especially after 6 months.

LncRNAs and regulated cell death in tumor cells.

Regulated Cell Death (RCD) is a mode of cell death that occurs through drug or genetic intervention. The regulation of RCDs is one of the significant reasons for the long survival time of tumor cells and poor prognosis of patients. Long non-coding RNAs (lncRNAs) which are involved in the regulation of tumor biological processes, including RCDs occurring on tumor cells, are closely related to tumor progression. In this review, we describe the mechanisms of eight different RCDs which contain apoptosis, necroptosis, pyroptosis, NETosis, entosis, ferroptosis, autosis and cuproptosis. Meanwhile, their respective roles in the tumor are aggregated. In addition, we outline the literature that is related to the regulatory relationships between lncRNAs and RCDs in tumor cells, which is expected to provide new ideas for tumor diagnosis and treatment.

The roles of Linc-ROR in the regulation of cancer stem cells.

Cancer stem cells (CSCs) are considered to be a kind of tumor cell population characterized by self-renewal, easy to metastasize and drug resistance, which play an indispensable role in the occurrence, development, metastasis and drug resistance of tumors, and their existence is an important reason for high metastasis and recurrence of tumors. Long non-coding RNAs (LncRNAs), which are more than 200 nucleotides in length, have a close relationship with the malignant progression of cancer.In recent years, abundant studies have reavling that LncRNAs are beneficial to the regulation of various cancer stem cells. Linc-ROR, as a newly discovered intergenic non-protein-coding RNA in recent years, is considered to be a key regulator affecting the development of human tumors. Dysregulation of Linc-ROR is related to stemness phenotype and functional regulation of cancer stem cells. For that, Linc-ROR has the potential to be used as a diagnostic biomarker for cancer patients and can serve as a clinically meaningful potential therapeutic target. In this review, we generalize the existing research results on the important role of Linc-ROR in regulation of CSCs.

USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance.

Ubiquitin­specific protease 39 (USP39), as one of the deubiquitinating enzymes (DUBs), exhibits aberrant an expression and has oncogenic functions in several types of cancer. However, the function and underlying molecular mechanisms of action of USP39 in ovarian cancer remain largely undetermined. The present study thus aimed to investigate whether USP39 is a promising tumor­associated gene and whether it could be a viable target for overcoming chemotherapeutic resistance in ovarian cancer. The present study identified that USP39 was highly expressed in ovarian cancer samples with carboplatin resistance. A series of functional assays revealed that the knockdown of USP39 in ES2 and SKOV3 cells significantly decreased cell proliferation, induced cell cycle arrest at the G2/M phase and impaired the cell colony formation ability. USP39 deficiency enhanced the carboplatin­induced apoptosis of the SKOV3 cells via the activation of poly­ADP ribose polymerase and caspase­3. USP39 knockdown led to the inhibition of cell migration and invasion. The opposite effects were observed when USP39 was overexpressed in the ES2 and SKOV3 cells. In vivo animal models revealed that the subcutaneous transplantation and intraperitoneal injection of USP39­overexpressing ES2 cells increased tumor burden with or without treatment with carboplatin. However, the knockdown of USP39 suppressed SKOV3 cell growth in vivo. Mechanistic analyses also demonstrated that USP39 induced the phosphorylation of extracellular signal­regulated kinase and AKT and increased the expression of epidermal growth factor receptor and cyclin B1. Collectively, the findings of this study suggest that USP39 may paly a vital role in regulating ovarian cancer malignant phenotypes and carboplatin resistance. Therefore, USP39 may prove to be a promising therapeutic target for patients with ovarian cancer.

Fabrication of Nickel Oxide Nanopillar Arrays on Flexible Electrodes for Highly Efficient Perovskite Solar Cells.

Semiconductor nanomaterials with controlled morphologies and architectures are of critical importance for high-performance optoelectronic devices. However, the fabrication of such nanomaterials on polymer-based flexible electrodes is particularly challenging due to degradation of the flexible electrodes at a high temperature. Here we report the fabrication of nickel oxide nanopillar arrays (NiO x NaPAs) on a flexible electrode by vapor deposition, which enables highly efficient perovskite solar cells (PSCs). The NiO x NaPAs exhibit an enhanced light transmittance for light harvesting, prohibit exciton recombination, promote irradiation-generated hole transport and collection, and facilitate the formation of large perovskite grains. These advantageous features result in a high efficiency of 20% and 17% for the rigid and flexible PSCs, respectively. Additionally, the NaPAs show no cracking after 500 times of bending, consistent with the mechanic simulation results. This robust fabrication opens a new opportunity for the fabrication of a large area of high-performance flexible optoelectronic devices.

Gene microarray analysis of lncRNA and mRNA expression profiles in patients with high­grade ovarian serous cancer.

High­grade ovarian serous cancer is known for its high rates of invasion and metastasis, and resultant high mortality rate. Therefore, research concerning biomarkers and underlying molecular mechanisms of high­grade ovarian serous cancer progression and prognosis are urgently required. Long non­coding RNAs (lncRNAs) have been the subject of an increasing number of studies, and certain lncRNAs have been demonstrated to serve an important function in the development and progression of various cancers, including HOX transcript antisense RNA, competing endogenous lncRNA 2 for microRNA let­7b, urothelial cancer associated 1, and H19, imprinted maternally expressed transcript (non­protein coding). However, few studies have investigated the differential expression of lncRNAs in high­grade ovarian serous cancer. In the present study, differences in lncRNA and mRNA expression profiles between high­grade ovarian serous cancer tissue samples and healthy fallopian tube tissue samples were investigated using microarray analysis, and the differential expression of lncRNAs and mRNAs was confirmed by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). Then, five abnormally expressed lncRNAs were selected, and the associations between these lncRNAs and ovarian cancer clinicopathological parameters were examined using RT­qPCR. The expression profiles of certain lncRNAs and mRNAs were confirmed to be altered between high­grade ovarian serous cancer tissues and healthy fallopian tube tissues. Furthermore, the expression levels of selected lncRNAs were associated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis. These lncRNAs and mRNAs may therefore be involved in the pathogenesis of high­grade ovarian serous cancer. The results of the present study provide an experimental foundation for further exploration of the value of these lncRNAs and mRNAs in the early diagnosis and treatment of high­grade ovarian serous cancer.

Linc-ROR induces epithelial-to-mesenchymal transition in ovarian cancer by increasing Wnt/ß-catenin signaling.

Long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) is an intergenic long non-coding RNA (lncRNA) previously shown to contribute to tumorigenesis in several malignancies. However, little is known about whether linc-ROR has a role in ovarian cancer progression. In this study, we found that linc-ROR expression was increased in high-grade ovarian serous cancer tissues compared with normal ovarian tissues or normal fallopian tube tissues. Furthermore, the level of linc-ROR expression was associated with ovarian cancer International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Linc-ROR promoted ovarian cancer cell proliferation both in vitro and in vivo, and contributed to cell migration and invasion. Linc-ROR knockdown in ovarian cancer cell lines inhibited the epithelial-to-mesenchymal transition (EMT) program, which led to ovarian cancer cell metastasis through the repression of canonical Wnt/ß-catenin signaling. Together, our results indicated that linc-ROR induces EMT in ovarian cancer cells and may be an important molecule in the invasion and metastasis of ovarian cancer.

High expression of S100P is associated with unfavorable prognosis and tumor progression in patients with epithelial ovarian cancer.

Accumulating evidence has demonstrated that S100P is involved in the tumorigenesis and progression of multiple cancers. In the current study, we evaluated the expression of S100P in epithelial ovarian cancer and assessed its relevance to clinicopathological characteristics. Moreover, we investigated the biological effects of S100P using A2780 and SKOV3 cells. S100P expression was significantly increased in epithelial ovarian cancer specimens compared with fallopian tube tissues and normal ovary tissues. And high expression of S100P in epithelial ovarian cancer samples was significantly associated with tumor stage (P<0.001), serum CA125 level (P=0.026), residual tumor (P<0.001), ascites (P<0.001) and lymph nodes metastasis (P<0.001). Multivariate Cox analysis showed that S100P expression was an independent prognostic factor of overall survival (OS) and progression free survival (PFS) (P=0.017 and 0.031, respectively). Functional assays showed that overexpression of S100P promoted cell proliferation and cell cycle progression but did not affect cell migration and invasion in A2780 and SKOV3 cells. These data suggest that S100P may contribute to tumor development in epithelial ovarian cancer and could be a useful marker for the prognosis of epithelial ovarian cancer patients.

Transparent p-type epitaxial thin films of nickel oxide.

Transparent p-type nickel oxide (NiO) thin films have been epitaxially grown on (0001) Al2O3 substrates by a chemical solution method of polymer-assisted deposition for the first time. The films have a high optical transparency of above 95% in the wavelength range of 350-900 nm.

[MicroRNA-16 regulates the proliferation, invasion and apoptosis of ovarian epithelial carcinoma cells in vitro].

OBJECTIVE: To study the role and mechanism of microRNA-16 (miR-16) in the proliferation, invasion and apoptosis of ovarian epithelial carcinoma cells in vitro. METHODS: The SKOV-3 cells were transfected with miR-16 mimics or negative control RNA (NC) by lipofectamine 2000. The expression of miR-16 was detected by real-time reverse transcription (RT)-PCR in SKOV-3 cells, and western blot was used to detect the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and bcl-2 protein. Methyl thiazolyl tetrazolium (MTT), 5-ethynyl-2'-deoxyuridine (EdU) and transwell assay were used to determine the proliferation and invasion abilities. And the rate of apoptotic cell was detected by flow cytometry method. RESULTS: (1) The expression level of miR-16 in the transfection cells group was significantly higher than that in NC group (125.93 ± 15.30 versus 0.78 ± 0.16, P < 0.01). (2) The relative expression level of VEGF protein in transfection cells, NC and blank control group was 0.58 ± 0.05, 1.22 ± 0.03, 1.20 ± 0.03, MMP-2 protein was 0.63 ± 0.03, 1.16 ± 0.03, 1.21 ± 0.03, and bcl-2 protein 0.52 ± 0.03, 1.19 ± 0.05, 1.28 ± 0.06, respectively. The level of VEGF, MMP-2 and bcl-2 protein in the transfection group were lower than those in other control groups, and there were significantly differences among them (all P < 0.01). (3) After transfected 4 days, the inhibition rate of cell proliferation in the transfection group was dramatically higher than that in NC group [(37.2 ± 6.2)% versus (3.6 ± 3.2)%, P = 0.001]. (4) The percentage rate of proliferative cells in the transfection, NC and blank control group was (12.3 ± 0.8)%, (23.4 ± 1.8)%, (31.1 ± 4.9)%. And it was lower in the transfection group (P < 0.05). (5) Decreased cells via the transwell member in the transfection group (6 ± 3) were detected as compared with NC group (40 ± 9) and blank control group (48 ± 8, P < 0.01). (6) Twenty-four hours after cultured in serum starvation and hypoxia, the rate of the viable and late apoptotic cells in the transfection group were significantly higher than those in NC group and blank control group [the rate of viable apoptotic cell was (16.9 ± 2.1)%, (10.3 ± 1.7)% and (9.0 ± 0.8)% respectively, P < 0.01; the rate of late apoptotic cell was (13.4 ± 3.3)%, (3.2 ± 1.8)% and (0.7 ± 0.6)% respectively, P < 0.01]. After cultured 48 hours, total apoptotic cells in the transfection group was significantly more than those in other groups (P < 0.01). CONCLUSION: miR-16 might inhibit the proliferation, invasion of ovarian epithelial carcinoma cells and enhance their sensitivity to apoptotic stimuli via downregulation of the expression of VEGF, MMP-2 and bcl-2 protein.

[Role of microRNA-21 in the proliferation and apoptosis of ovarian epithelial carcinoma cells].

OBJECTIVE: To investigate the role and mechanism of microRNA-21(miR-21) in the proliferation and apoptosis of ovarian epithelial carcinoma cells. METHODS: A short-hairpin RNA specifically targeting miR-21 plasmid was constructed, and the recombinant was identified by restriction endonuclease analysis and DNA sequencing. Three experimental groups were included, transfection group (transfected with pSIREN-miR-21), negative control group (transfected with pSIREN-miR-21-neg) and blank control group (without transfection plasmid). The expression of miR-21 was detected by stem-loop real-time reverse transcription (RT)-PCR in OVCAR3 cells, and western blot was used to detect the expression of programmed cell death 4 (PDCD4) protein. Tethyl thiazolyl tetrazolium(MTT) and flow cytometry method were used respectively. RESULTS: Recombinant plasmid (pSIREN-miR-21) was constructed successfully and identified by restriction endonuclease analysis and DNA sequencing. The relative expression level of miR-21 in cells transfection, negative control and blank control group was 0.26 ± 0.08, 1.26 ± 0.21 and 1.00 respectively. The level of miR-21 in the cells in transfection group was significantly lower than those in the negative control and blank control group (P < 0.01). The gray scale of PDCD4 protein was 1443 ± 33, 858 ± 19 and 846 ± 16 in the transfection group, negative control and blank control group respectively. The value of PDCD4 in transfection group was higher than other control groups, and there were significantly difference among them(P < 0.01). Moreover, the optical density of the cells in transfection group was 0.661 ± 0.015, significantly lower than those in two control groups (0.848 ± 0.150 for negative control, 0.935 ± 0.133 for blank control, P < 0.01). Forty-eight hours after transfection, the rate of viable apoptotic cell was significantly higher than negative control and blank control group [(25.821 ± 0.763)% vs. (0.010 ± 0.003)% vs. (0.238 ± 0.023)%; P < 0.01]; 72 hours after transfection, the rates of viable apoptotic cell and necrotic cell were all higher than the two control groups [the rate of viable apoptotic cell was (30.480 ± 0.821)%, (7.792 ± 0.312)% and (7.033 ± 0.257)% respectively (P < 0.01); the rate of necrotic cell was (3.558 ± 0.211)%, (1.557 ± 0.067)% and (1.049 ± 0.028)%, respectively (P < 0.01)]. CONCLUSION: miR-21 might play an important role in the proliferation and apoptosis of ovarian epithelial carcinoma cells through negatively control the expression of PDCD4.

miR-21 down-regulation promotes apoptosis and inhibits invasion and migration abilities of OVCAR3 cells.

PURPOSE: To investigate the influence of miR-21 down-regulation on cell proliferation, apoptosis, invasion and migration of ovarian papillary adenocarcinoma cell lines (OVCAR3). METHODS: Short-hairpin RNA (shRNA), specifically targeting miR-21, was constructed and transfected into OVCAR3 cells using the pSIREN-RetroQ linear vector (pSIREN-miR-21). The expression of miR-21 was detected with stem-loop real-time RT-PCR in OVCAR3 cells. Cell proliferation and apoptosis were monitored using the MTT assay and flow cytometry, respectively. Cell migration and invasion were assessed using the transwell migration and scratch-wound assay, respectively. Western-bloting was used for PDCD4 protein expression. RESULTS: pSIREN-miR-21 suppressed miR-21 expression in OVCAR3 cells. miR-21 expression levels in pSIREN-miR-21 cells was 0.3 ± 0.1, which was significantly lower when compared with pSIREN-miR-21-Neg and control groups (P < 0.01). Cell inhibition rate in the pSIREN-miR-21 group was higher than the control group (29.4% vs 9.0%, P < 0.01), as was the percentage of apoptotic and necrotic cells. By transwell migration assay, the number of cells migrating in the pSIREN-miR-21 group was significantly lower than in the control group. In addition, fewer cells were observed in the wounded area of the pSIREN-miR-21 group following the scratch-wound assay. PDCD4 expression was increased in OVCAR-3 cells transfected by pSIREN-miR-21 compared with vector-control transfected cells. Moreover, the optical density of the transfected cells was significantly lower than the two control groups. CONCLUSION: Down-regulation of miR-21 dramatically increased apoptotic cell death and decreased cell proliferation, invasion and migration in OVCAR3 cells. MiR-21 may play an important role in the biological behaviors of epithelial ovarian carcinoma cells through negative control of the expression of PDCD4.

MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein.

Ovarian cancer, especially epithelial ovarian cancer (EOC), which accounts for 90% of ovarian cancer, continues to be the leading cause of death among gynecological malignancies. However, the factors associated with its malignant biological behavior are still poorly understood. Accumulating evidence suggests that microRNAs (miRNAs), regulating diverse biological processes, may play an important role in tumorigenesis and development. miR-21 has been frequently observed to be aberrantly overexpressed in various tumors. Using real-time PCR, we confirmed that miR-21 was significantly overexpressed in human EOC tissues and cell lines. The overexpression of miR-21 correlated with histological differentiation, clinicopathological stage, and lymph node metastasis, and we showed that knockdown of miR-21 by an inhibitor caused a significant reduction in cell proliferation and decrease in cell migration and invasion abilities. Furthermore, we demonstrated that knockdown of miR-21 significantly increased the expression of PTEN, a known tumor suppressor in ovarian cancer. Collectively, our findings suggest miR-21 may be important in the initiation and progression of EOC as an oncomiR, likely through regulating PTEN.

The role of TSH for 18F-FDG-PET in the diagnosis of recurrence and metastases of differentiated thyroid carcinoma with elevated thyroglobulin and negative scan: a meta-analysis.

PURPOSE: To establish the effects of TSH stimulation on the uptake of fluorine-18-labeled 2-fluoro-2-deoxy-d-glucose for differentiated thyroid carcinoma (DTC) with thyroglobulin-positive and scan negative metastases. MATERIALS AND METHODS: We searched the MEDLINE, EMBASE and the Cochrane Library for prospective controlled trials using TSH stimulation as an intervention. The outcomes of positron emission tomography (PET)-positive lesions, tumor-to-background ratio, maximum standard uptake value of the detected lesions were extracted and synthesized, and patients with the altered clinical management were studied. A meta-analysis was carried out using the Review Manager software. RESULTS: Seven prospective controlled clinical trials with 168 patients were found. All studies had a low risk of bias. PET scans under TSH stimulation versus thyroid hormone suppression showed statistically significant differences in the number of patients with PET true-positive lesions (odds ratio (OR) 2.45, 95% confidence interval (CI) 1.23-4.90) and in the number of the PET-detected lesions (OR 4.92, 95% CI 2.70-8.95) and tumor-to-background ratios. PET scans taken under TSH stimulation altered clinical management in altogether 12/130 (9%) patients in five paired studies (OR 2.40, 95% CI 1.11-5.22). CONCLUSION: The data indicate that TSH stimulation should be recommended for DTC patients undergoing PET scanning in these circumstances. However, further well-designed studies emphasizing on the clinical significance of altered management by PET under TSH stimulation are needed.

[Expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in human and nude mouse ectopic endometrium and the effect of estrogen and progestin on their expression].

OBJECTIVE: To explore the roles of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinase-1(TIMP-1) in the pathogenesis of endometriosis and the effects of estrogen and progestin on their expression. METHODS: Immunohistochemistry and RT-PCR were employed to detect the expression of MMP-1 and TIMP-1 in the ectopic tissues of 35 patients with endometriosis, 22 eutopic endometrium tissues from women with endometriosis and 28 normal controls. Fifty-nine nude mice were injected with human late secretory endometrial chippings and randomized into estrogen group, progestin group, estrogen-progestin group and control group with corresponding treatments. The implantation rates and graft morphology were observed and MMP-1 and TIMP-1 expressions in the grafts detected by immunohistochemistry. RESULTS: Typical endometrial glands and stroma were observed in all the groups with comparable implantation rates. The administration of progestin was associated with multiple peritoneal implantation sites and significantly larger implants. The transplanted endometria showed proliferative or secretory changes with estrogen or progestin administration. MMP-1 expression significantly increased and TIMP-1 expression decreased with increased MMP-1/TIMP-1 ratio in human and nude mouse ectopic endometria in comparison with those in normal endometria (P<0.05, P<0.01). MMP-1 expression was higher in estrogen and estrogen-progestin groups than in the control group, and was lower in the 3 sexual hormone-treated groups than in the control group. MMP-1 mRNA expression in the eutopic endometrium was significantly higher than that in the normal endometria. CONCLUSION: Progestrin can not inhibit MMP-1 expression or the effect of estrogen on ectopic endometrium known as progestin resistance. The high expression of MMP-1 and low expression of TIMP-1 in endometriotic tissues confer strong invasiveness of ectopic endometrial tissue, especially in eutopic endometrial tissue, and may play an important role in the pathogenesis of endometriosis.

[Expression of microRNA-21 in ovarian epithelial carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression of microRNA-21(miR-21) in ovarian epithelial carcinoma and its association with the clinicopathological features. METHODS: The expression of miR-21 was detected by Stem-loop real-time RT-PCR in 48 cases of ovarian epithelial carcinomas, 24 cases of benign ovarian epithelial tumors and 15 cases of normal ovarian tissues. RESULTS: The relative expression level of miR-21(2-(DeltaDelta)CT) was 4.849-/+1.813 in the ovarian epithelial carcinomas, significantly higher than that in the benign ovarian tumors and normal ovarian tissues (P<0.01), but comparable between the latter two groups. The expression of miR-21 was not correlated to the histological type, but increased significantly with the progression of the clinical stages and histological grading (P<0.01), showing a close correlation to lymphatic metastasis. CONCLUSION: MiR-21 might play a role as an oncogene in the tumorigenesis and development of ovarian epithelial carcinoma, and is possibly correlated to the progression and prognosis of ovarian epithelial carcinoma.

[Expression of matrix metalloproteinase-9 and tumor necrosis factor-alpha in the placenta of patients with pregnancy-induced hypertension].

OBJECTIVE: To investigate the role of matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of pregnancy-induced hypertension (PIH). METHODS: The placenta samples were collected from 57 patients with PIH and 24 normal pregnant women. Immunohistochemical staining was used to examine positive expression of MMP-9 and TNF-alpha in these samples. RESULTS: The positive expression of MMP-9 in the normal group was significantly higher than that in patients with moderate or severe PIH (P<0.01), while no significant difference was found between normal pregnant women and patients with mild PIH (P>0.05), and expression decreased drastically with the progression of PIH (P<0.05). The expression of TNF-alpha in the patients with mild, moderate and severe PIH groups were significantly higher than that in the normal group (P<0.05, P<0.01 and P<0.01, respectively), and the differences were also significant between the PIH groups of different severities (P<0.01). No correlation was found between MMP-9 and TNF-alpha expressions in the normal and mild PIH groups (r=0.287, P>0.05; r=0.382, P>0.05), in the patients with moderate and severe PIH, MMP-9 expression showed inverse correlation with TNF-alpha expression (r=-0.563, P<0.05; r=-0.681, P<0.01). CONCLUSION: Lowerd MMP-9 expression in syncytiotrophoblast might result in defective nidation in the placenta where local ischemia and hypoxia cause abnormal TNF-alpha elevation, which might be one of the important factors inducing PIH.