OBJECTIVE: To investigate the clinical characteristics and genetic etiology in a fetus with 12q14 microdeletion syndrome. METHODS: A fetus diagnosed with 12q14 microdeletion syndrome at Wenzhou People's Hospital in July 2019 was selected as the study subject. The fetus was from a twin pregnancy by in vitro fertilization-embryo transfer, with ultrasound findings including growth restriction, cleft lip/palate, ventricular septal defect, tricuspid regurgitation, and pericardial effusion. Clinical data and family history were collected. Amniotic fluid sample was collected from both twins, and peripheral blood samples were obtained from their parents. Amniocytic karyotyping analysis and chromosomal microarray analysis (CMA) were performed, and familial validation was conducted. This study was approved by the Medical Ethics Committee of Wenzhou People's Hospital (Ethics No.: KY-202408-034). RESULTS: Prenatal ultrasound showed no significant abnormality in one of the twins, whilst the other twin exhibited severe growth restriction accompanied by cleft lip/palate, ventricular septal defect, tricuspid regurgitation, and pericardial effusion. Karyotyping and CMA analyses of first twin showed no abnormalities, whilst the second twin had a chromosomal karyotype of 46,XN,t(3;12)(q26.3;q14), and CMA revealed a 4.9 Mb deletion in the 12q14.3-q15 region (arr[hg19]12q14.3q15(65,574,059_70,488,106)x1). Karyotyping and CMA analyses of both parents revealed no abnormalities, confirming that the fetus deletion was de novo in origin. Literature review suggested that prenatal diagnosis of 12q14 microdeletion syndrome has been extremely rare. CONCLUSION The fetus was diagnosed with 12q14 microdeletion syndrome. This de novo deletion may have dervied from chromosomal translocation. As a first-tier prenatal diagnostic technique, CMA can effectively detect microdeletion/microduplications missed by conventional karyotyping analysis.
Humans ; Female ; Pregnancy ; Chromosome Deletion ; Chromosomes, Human, Pair 12/genetics* ; Karyotyping ; Adult ; Prenatal Diagnosis ; Chromosome Disorders/diagnosis* ; Ultrasonography, Prenatal ; Fetus ; Male

Objective To analyze the characteristics,causes,influencing factors of compensation,and appraisal features of second-instance medical malpractice cases involving cardiovascular diseases in Henan Province from 2017 to 2022,and to provide reference for forensic appraisal and judicial trial.Methods Cases were retrieved from China Judgments Online between 2017 and 2022.A total of 1,957 documents were reviewed,including 1,397 medical malpractice cases and 130 cardiovascular disease cases.Results The total compensation awarded in these second-instance cases was 27.04 million yuan,with a median of 158,600 yuan.Cases involving patient death accounted for 80.00％(104/130).Among 107 cases with first-instance appraisals,55.14％(59/107)raised objections,while 74.62％(97/130)of the second-instance trials upheld the original judgment.The most common degree of responsibility borne by medical institutions was secondary responsibility(41.54％,54/130).The top three medical faults were:inadequate observation and management of patient conditions(46.15％),omission of auxiliary examinations(37.50％),and insufficient notification(36.54％).In terms of violations-including medical record documentation,inappropriate treatment,misdiagnosis or missed diagnosis,out-of-scope practice,and improper medication use-the actual proportions in judgments(24/113,34/113,12/113,7/113,14/113)were all significantly lower than the patients' claims(all P＜0.05).Conclusion Cardiovascular medical malpractice cases in second-instance trials involve substantial compensation and a high proportion of death outcomes.Both medical institutions and patients should pay greater attention to first-instance trials.Appraisal organizations should proactively provide explanation and education regarding issues likely to raise patient doubts,thereby reducing unnecessary appeals.They should also avoid hasty revisions of appraisal opinions when faced with objections and instead focus on improving the quality and credibility of appraisals.In determining medical faults,emphasis should be placed on evaluating whether there was inadequate patient monitoring and management,omission of auxiliary examinations,and insufficient notification.

Objective To analyze the characteristics,causes,influencing factors of compensation,and appraisal features of second-instance medical malpractice cases involving cardiovascular diseases in Henan Province from 2017 to 2022,and to provide reference for forensic appraisal and judicial trial.Methods Cases were retrieved from China Judgments Online between 2017 and 2022.A total of 1,957 documents were reviewed,including 1,397 medical malpractice cases and 130 cardiovascular disease cases.Results The total compensation awarded in these second-instance cases was 27.04 million yuan,with a median of 158,600 yuan.Cases involving patient death accounted for 80.00％(104/130).Among 107 cases with first-instance appraisals,55.14％(59/107)raised objections,while 74.62％(97/130)of the second-instance trials upheld the original judgment.The most common degree of responsibility borne by medical institutions was secondary responsibility(41.54％,54/130).The top three medical faults were:inadequate observation and management of patient conditions(46.15％),omission of auxiliary examinations(37.50％),and insufficient notification(36.54％).In terms of violations-including medical record documentation,inappropriate treatment,misdiagnosis or missed diagnosis,out-of-scope practice,and improper medication use-the actual proportions in judgments(24/113,34/113,12/113,7/113,14/113)were all significantly lower than the patients' claims(all P＜0.05).Conclusion Cardiovascular medical malpractice cases in second-instance trials involve substantial compensation and a high proportion of death outcomes.Both medical institutions and patients should pay greater attention to first-instance trials.Appraisal organizations should proactively provide explanation and education regarding issues likely to raise patient doubts,thereby reducing unnecessary appeals.They should also avoid hasty revisions of appraisal opinions when faced with objections and instead focus on improving the quality and credibility of appraisals.In determining medical faults,emphasis should be placed on evaluating whether there was inadequate patient monitoring and management,omission of auxiliary examinations,and insufficient notification.

Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.

Objective:To investigate the role of an inflammatory microenvironment induced by Porphyromonasgingivalis ( P. gingivalis) in the occurrence of esophageal squamous cell carcinoma (ESCC) in mice. Methods:A total of 180 C57BL/6 mice were randomly divided into 6 groups, i.e. control group, P. gingivalis group, 4NQO group, 4NQO + P. gingivalis group, 4NQO + P. gingivalis + celecoxib group, and 4NQO + P. gingivalis + antibiotic cocktail (ABC, including metronidazole, neomycin, ampicillin, and vancomycin) group, with 30 mice in each group, using the random number table. All mice were normalized by treatment with ABC in drinking water for 2 weeks. In the following 2 weeks, the mice in the control group and the P. gingivalis group were given drinking water, while the other 4 groups were treated with 30 μg/ml 4NQO in the drinking water. In weeks 11-12, the mice in the P. gingivalis group, the 4NQO + P. gingivalis group, the 4NQO + P. gingivalis + celecoxib group, and the 4NQO + P. gingivalis + ABC group were subjected to ligation of the second molar in oral cavity followed by oral P. gingivalis infection thrice weekly for 24 weeks in weeks 11-34. In weeks 13-34, the mice in 4NQO + P. gingivalis+celecoxib group and 4NQO + P. gingivalis + ABC group were administered with celecoxib and ABC for 22 weeks, respectively. At the end of 34 weeks, gross and microscopic alterations were examined followed by RT-qPCR and immunohistochemistry to examine the expression profiles of inflammatory- and tumor-molecules in esophagi of mice. Results:At 34 weeks, 4NQO treatment alone did not affect the foci of papillary hyperproliferation, diseased area, and the thickness of the esophageal wall, but significantly enhanced the foci of hyperproliferation (median 1.00, P＜0.05) and mild/moderate dysplasia (median 2.00, P＜0.01). In addition, the expression levels of IL-6 [8.35(3.45,8.99)], IL-1β [6.90(2.01,9.72)], TNF-α [12.04(3.31,14.08)], c-myc [2.21(1.80,3.04)], pSTAT3, Ki-67, and pH2AX were higher than those in the control group. The pathological changes of the esophageal mucosa were significantly more overt in the 4NQO + P. gingivalis group in terms of the foci of papillary hyperproliferation (median 2.00), diseased area (median 2.51 mm 2), the thickness of the esophageal wall (median 172.52 μm), the foci of hyperproliferation (median 1.00, P＜0.05), and mild/moderate dysplasia (median 1.00, P＜0.01). In mice of the 4NQO + P. gingivalis group, the expression levels of IL-6 [12.27(5.35,22.08)], IL-1β [13.89(10.04,15.96)], TNF-α [19.56(6.07,20.36)], IFN-γ [11.37(8.23,20.07)], c-myc [2.62(1.51,4.25)], cyclin D1 [4.52(2.68,7.83)], nuclear pSTAT3, COX-2, Ki-67, and pH2AX were significantly increased compared with the mice in the control group. In mice of the 4NQO + P. gingivalis group, the diseased area, invasive malignant foci as well as pSTAT3 and pH2AX expression were significantly blunted by celecoxib. Treatment with ABC markedly reduced the papillary hyperproliferative foci, invasive malignant foci, and pSTAT3 expression but not pH2AX. Conclusions:P. gingivalis promotes the occurrence of esophageal squamous cell carcinoma in mice by inducing an inflammatory microenvironment primed with 4NQO induced DNA damage. Clearance of P. gingivalis with ABC or anti-inflammatory intervention holds promise for prevention of esophageal squamous cell malignant pathogenesis via blockage of IL-6/STAT3 signaling and amelioration of inflammation.

Programmed cell death (PCD) is a genetically determined, active and orderly cell death in the organism, and it affects the evolution of the organism, maintenance of its homeostasis, and development of several tissues and organs. The abnormal regulation of this process is closely related to various human diseases, including cancer. The identified pathways of PCD include apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis, which can be activated when cells are stimulated by various internal and external environmental factors. These pathways can induce cell death or maintain cell survival in kidney cancer cells under the regulation of various signaling molecules, thus affecting tumor progression or therapeutic efficacy. In this paper, the role of these PCD pathways in the development of kidney cancer was reviewed in light of recent research advances to provide new directions for the in-depth study of the pathogenesis of kidney cancer and the development of targeted antitumor drugs.

Objective:To investigate the effects of Porphyromonas gingivalis ( P. gingivalis) fimbrillin (FimA) on the progression of esophageal squamous cell carcinoma (ESCC). Methods:Wild-type P. gingivalis and fimA gene-deleted P. gingivalis ( fimA-/-P. gingivalis) were used to infect ESCC cells after morphology and PCR identification. Immunofluorescence, CCK-8 and Transwell chamber were used to detect the effects of FimA on the infectivity of P. gingivalis and it influences on cell invasion, proliferation and migration. Western blot was used to detect pSmad2/3 changes. The growth of tumor was detected in a nude mouse model bearing subcutaneous tumor. Results:Deletion of FimA might reduce the interbacterial adhesion of P. gingivalis. Compared with wild-type P. gingivalis, less fimA-/-P. gingivalis could infect NE6-T cells. Moreover, the proliferation, migration and invasion of NE6-T and KYSE30 cells as well as the activation of pSmad2/3 induced by P. gingivalis were inhibited after deletion of FimA. The growth of KYSE30 infected by fimA-/-P. gingivalis in nude mice was significantly slower than that of the wild-type P. gingivalis group. Conclusions:FimA mediated the effects of P. gingivalis on promoting the evolution of ESCC and was a potential target molecule to block the tumor-promoting effect of P. gingivalis.

Objective: To isolate and identify Prevotella nigrescens (P.nigrescens) in gingival crevicular fluid of patients with chronic periodontitis and to analyze its tumor-promoting role in esophageal squamous cell carcinoma (ESCC). Methods: Samples of gingival crevicular fluid were collected from patients with chronic periodontitis and cultured on GAM agar medium under anaerobic conditions. Black colonies on GAM agar plates were picked for subculture, and then the bacteria were isolated and purified. Bacterial identification was conducted using Gram staining and 16S rDNA sequencing analysis. The isolated bacterial species was used to infect ESCC NE6-T cells and the changes in biological characteristics of the infected cells were evaluated. Results: Multiple bacterial colonies were observed after anaerobic culturing of gingival crevicular fluid samples for 120 h on GAM agar plates. A single bacterial colony with pure black and smooth appearance was obtained from grey black bacterial colonies with streak method. It was a Gram-negative bacterium with bead-like shape. It showed 99.78% 16S rDNA sequence identity with P. nigrescens F0103 and was named P. nigrescens LY01. P. nigrescens LY01 infection promoted the in vitro proliferation, migration and invasion of NE6-T cells and the growth of subcutaneous xenograft in nude mice. In addition, it could also induce the upregulation of Ki67 and activation of p-STAT3. Conclusions P. nigrescens inhabiting in gingival sulcus might promote the progression of ESCC in human with chronic periodontitis.

Objective To investigate the effects of sodium butyrate on the activity of RAW264.7 cells and the osteoclast differentiation.Methods The RAW264.7 cells were treated by sodium butyrate at concentrations of 0,0.25,0.50,1.00,2.00,3.00,4.00 and 5.00 mmol/L,with 3 double pores for each concentration.The cytotoxicity of sodium butyrate on RAW264.7 cells was detected by a CCK-8 kit.The effects of sodium butyrate (0,0.25,0.50 and 1.00 mmol/L) on apoptosis of RAW264.7 cells were detected by Hoechst33342 staining.RAW264.7 cells were induced into osteoclasts by osteoclast differentiation factors.The experiment was carried out in 2 groups (n =3).After induced maturation,the experimental group was treated with 1.00 mmol/L sodium butyrate and the control medium was added only with the same volume of solvent.The number of osteoclasts and the area of bone resorption were observed and compared.The differentiation of RAW264.7 cells was detected by tartrate-resistant acid phosphatase (TRAP) staining.Western blotting was used to detect the effects of sodium butyrate (0,0.25,0.50 and 1.00 mmol/L) on NF-κB-related signaling pathway in RAW264.7 cells.Results Compared with the group of 0 mmol/L sodium butyrate,the activity of cells treated with 1.00,2.00,3.00,4.00 and 5.00 mmol/L sodium butyrate for 24 h was significantly decreased (P ＜ 0.05).Treatment with 1.00 mmol/L sodium butyrate for 24 h induced apoptosis.The number of osteoclasts in the control group and the experimental group were 9.33 ± 2.08 and 4.67 ± 1.16,respectively,showing a significant difference between the 2 groups (t =3.395,P =0.027).The percentages of bone resorption area in the control group and the experimental group were 52.43％ ± 5.38％ and 14.28％ ± 2.72％,respectively,also showing a significant difference between the 2 groups (t =10.970,P ＜ 0.001).Western blot results showed that,compared with other concentrations of sodium butyrate,treatment with 1 mmol/L sodium butyrate on RAW264.7 cells for 24 h led to an increase in the expression levels of cytoplasmic p65,B lymphoma-2 associated X protein and cleaved-caspase 3 and the acetylation of Histone H3 but a decrease in the phosphorylation level of α/β subunit of NF-κB kinase.Conclusions With the increased concentration of sodium butyratecan,the activity of NF-κB may be suppressed and the number of apoptotic cells may increase.1.00 mmol/L sodium butyrate can reduce osteoclast formation and bone resorption area.

Cervical intraepithelial neoplasia is a preinvasive lesion of cervical carcinoma associated with HPV infection.It can be classified as low or high grade according to the degree of the lesion.Low grade lesion includes HPV infection and CIN1,and high grade lesion includes CIN2～3.HPV infection and CIN have become very common among fertile women,so more and more attention has been paid to the influence that HPV infection,cervical lesion and their treatments would have on pregnancy.HPV infection may increase during pregnancy period.Tough there will be more chances for the vaginal delivery infants to be exposed to HPV,it is not proper to draw a conclusion that cesarean must be performed for all HPV infected pregant women.If CIN1 is found during pregnancy,observation and close follow-up post partum should be advised.Pregnancy may not deteriorate CIN2～3,but clear diagnosis should be made during pregnancy if colposcopy examination result is not satisfactory or great doubt for invasive cancer exits.In this case,conization during the second semester of the pregancy is advised,which may increase the cesarean rate.Conservative therapy for CIN has not significant influnce on fertility,while cold knife conization and LEEP conization may increase the premature delivery rate,which may be associated with premature ruption of fetal membrane.