[Ocular surface adverse reactions of antitumor-targeted drugs].

With the extensive application of targeted drugs, the survival rate of cancer patients has been significantly improved. However, adverse reactions to the drugs have also become apparent, especially those affecting the ocular surface, which can severely impact patients' vision and quality of life. The article systematically analyzes a variety of targeted drugs, including epidermal growth factor receptor inhibitors, human epidermal growth factor receptor 2 inhibitors, fibroblast growth factor receptor inhibitors, selective estrogen receptor modulators, vascular endothelial growth factor receptor inhibitors, aromatase inhibitors, proteasome inhibitors, antibody-drug conjugates, Bruton's tyrosine kinase inhibitors, FMS-like tyrosine kinase 3 inhibitors, and cyclin-dependent kinase inhibitors, and discusses their adverse reactions on the ocular surface. The review emphasizes the role of clinicians in monitoring and managing patients' ocular surface health and the importance of early diagnosis and intervention to ensure that patients receive optimal visual protection while undergoing antitumor treatment.

MRI radiomics predicts the efficacy of EGFR-TKI in EGFR-mutant non-small-cell lung cancer with brain metastasis.

AIM: To develop and validate models based on magnetic resonance imaging (MRI) radiomics for predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in EGFR-mutant non-small-cell lung cancer (NSCLC) patients with brain metastases. MATERIALS AND METHODS: 117 EGFR-mutant NSCLC patients with brain metastases who received EGFR-TKI treatment were included in this study from January 1, 2014 to December 31, 2021. Patients were randomly divided into training and validation cohorts in a ratio of 2:1. Radiomics features extracted from brain MRI were screened by least absolute shrinkage and selection operator (LASSO) algorithm. Logistic regression analysis and Cox proportional hazard regression analysis were used to screen clinical risk factors. Clinical (C), radiomics (R), and combined (C + R) nomograms were constructed in models predicting short-term efficacy and intracranial progression-free survival (iPFS), respectively. Calibration curves, Harrell's concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the performance of models. RESULTS: Overall response rate (ORR) was 57.3% and median iPFS was 12.67 months. The C + R nomograms were more effective. In the short-term efficacy model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.860 (0.820-0.901, 95%CI) and 0.843 (0.783-0.904, 95%CI). In iPFS model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.837 (0.751-0.923, 95%CI) and 0.850 (0.763-0.937, 95%CI). CONCLUSION: The C + R nomograms were more effective in predicting EGFR-TKI efficacy of EGFR-mutant NSCLC patients with brain metastases than single clinical or radiomics nomograms.

[Cryotherapy combined with local spraying of isoniazid for the treatment of nasopharyngeal tuberculosis: a case report].

Nasopharyngeal tuberculosis refers to the tuberculosis in the nasopharynx, which is mainly treated with systemic chemotherapy with anti-tuberculosis drugs. Here, we reported a case of nasopharyngeal tuberculosis treated by cryosurgery combined with local spraying of isoniazid on the basis of systemic chemotherapy with anti-tuberculosis drugs. By reviewing the case data and relevant literature, we understood the clinical manifestations, diagnosis and differential diagnosis of the disease, improved everyone's understanding of the disease, and proposed a new method of cryosurgery combined with local spraying of isoniazid for the treatment of nasopharyngeal tuberculosis for clinical discussion.

[Application of the two-step sentinel lymph node biopsy with double-tracer in early staged endometrial cancer].

Objective: To explore the feasibility and clinical value of sentinel lymph node (SLN) biopsy through cervix-uterine combined two-step injection with two tracers in patients with early stage endometrial cancer. Methods: From July 2019 to April 2021, a total of 73 patients, aged (54.2±3.3) year, who were preoperatively diagnosed as stage Ⅰ-Ⅱ endometrial cancer (including 56 low-risk patients and 17 medium-high risk patients) in Affiliated Hospital of Qingdao University were selected. According to the different sites of tracer injection, the patients were randomly divided into three groups: cervical injection group (25 cases): 1 ml of nano-carbon was used to inject at 3 and 9 o'clock in the cervix; uterine injection group (21 cases): the magnetic resonance imaging examination was performed to determine the location of the lesion, and 4 ml of methylene blue was injected into the uterine body at 2 sites where the lesion was located; combined injection group (27 cases): cervical injection of nano-carbon (1 ml) combined with uterine injection of methylene blue (4 ml). The SLN in all patients were identified under laparoscopy, removed, and followed by frozen pathological examination. Pathological ultra-staging was performed if the postoperative pathological outcome of SLN was negative. The total detection rate of SLN, bilateral pelvic SLN detection rate, sensitivity, negative predictive value, and location of SLN in each group were calculated and compared. Results: (1) In 73 patients with endometrial cancer, the overall detection rate of SLN was 88% (64/73), the detection rate of bilateral pelvic SLN was 67% (49/73), and the detection rate of para-aortic SLN was 49% (36/73). The overall detection rate of SLN (71%, 15/21) and bilateral pelvic SLN (43%, 9/21) in the intrauterine injection group were significantly lower than those in the cervical injection group [92% (23/25), 76% (19/25), respectively] and the combined injection group [96% (26/27), 78% (21/27), respectively; all P<0.05]; the detection rate of para-aortic SLN in the cervical injection group (28%, 7/25) was significantly lower than those in the intrauterine injection group and combined injection group [52% (11/21) and 67% (18/27), respectively; both P<0.05]. Among 73 cases with endometrial cancer, 9 had lymph node metastasis confirmed by postoperative pathological examination, 8 of them had lymph node metastasis detected by SLN and 1 had no lymph node metastasis detected by SLN, with a total sensitivity of 89% and a negative predictive value of 98%. The sensitivity and negative predictive value of cervical injection group and combined injection group were 100%, while the sensitivity and negative predictive value of intrauterine injection group were 67% and 95%. Among 56 low-risk patients, only one patient with lymph node metastasis was confirmed by postoperative pathology by SLN detection, and the metastasis rate was 2% (1/56), and the sensitivity and negative predictive value were 100%. Lymph node metastasis was confirmed in 8 of 17 patients (8/17) with a sensitivity of 88% and a negative predictive value of 90%. (2) A total of 459 SLN were detected in 73 endometrial cancer patients, with the highest proportion of external iliac (33.3%, 153/459).The obturator foramen was 25.3% (116/459), para-aortic 19.6% (90/459), iliac 12.0% (55/459), and presacral 9.8% (45/459). The proportion of para-aortic SLN in the cervical injection group was 12.4% (21/169), which were significantly lower than that in the intrauterine injection group and the combined injection group [27.4% (26/95) and 22.1% (43/195), respectively; both P<0.05]. (3) Pathological super-staging results: among 64 patients with negative SLN routine paraffin pathology, 4 cases of lymph node micro-metastases and 1 case of isolated tumor cell metastasis were detected, and the SLN micro-metastases rate was 8% (5/64), including 2 cases of low-risk patients and 3 cases of medium-high risk patients. Conclusions: SLN biopsy has high sensitivity and negative predictive value in patients with early endometrial cancer and could be used as an alternative to systematic lymph node dissection in low-risk patients. The SLN mapping through cervical-uterine combined injection could further improve the detection rate effectively and avoid the missed detection of positive para-aortic lymph node, especially for high-risk patients or patients with fundal tumor involvement.

[A case of microsporidial keratitis].

A case of keratitis caused by microsporidia infection was reported. A 57-year-old female patient, without any obvious predisposing cause, presented with eye redness, eye abrasion and vision loss for one year in the left eye. The patient was diagnosed with viral keratitis based on laboratory examinations and clinical symptoms two months ago in our hospital. He was given outpatient treatment for antivirus. Two months later, he was admitted to our hospital with worsened condition that presented with corneal ulcer. After admission, corneal scraping examination was performed for the detection of microsporidia with calcofluor white (CFW) and Ziehl-Neelsen staining, the smear revealed multiple oval spore-like structures, with acid-fast positive and showed blue fluorescence on potassium hydroxide with CFW stain, confirming a diagnosis of microsporidial keratitis in the left eye. Treatment: topical use of ofloxacin eye ointment and voriconazole eye drops was not effective, and then penetrating keratoplasty was performed, and the patient's condition was stable after surgery. At present, they are still in treatment and follow-up.

[Value of ultrasonography in diagnosis and classification of Masson's tumor].

A retrospective analysis was performed on 11 cases of Masson's tumor admitted to Liaocheng People's Hospital from January 2010 to July 2021. Among them, there were 4 males and 7 females, aged from 14 to 62 years, with a medical history of 1 to 24 months. All of the patients complained of touching the mass under the skin. In this group, 9 cases were pure form, 1 case was mixed form and 1 case was extravascular form. Ultrasound imaging can reflect the characteristics of Masson's tumor to a certain extent, which has a certain value in the diagnosis, classification and differential diagnosis.

[The combination of YAP/TAZ predicts the clinical prognosis in patients with cholangiocarcinoma after radical resection].

Objective: Cholangiocarcinoma (CCA) is a malignant tumor derived from bile duct epithelial cells with extremely poor prognosis. The Hippo-Yes-associated protein (YAP)/transcription activator with PDZ binding motif (TAZ) signaling plays a critical role in cancer stem cell biology. Previous studies have shown that the positive expression of YAP/TAZ in CCA predicts larger tumor size and unfavorable clinical outcomes. We aim to evaluate the prognostic value of YAP/TAZ detection in CCA patients. Methods: CCA patients who underwent radical resection were retrospectively analyzed at our institution from January 2011 to June 2016. Postoperative pathological specimens were scored by YAP/TAZ immunohistochemical staining. The prognostic value of YAP/TAZ was analyzed by multivariate Cox-proportional hazards model. Results: A total of 91 CCA patients were enrolled. During a median follow-up time of 11.0 months, 69.2% patients relapsed and 45.1% died. The median OS and DFS were 10.7 months and 8.8 months respectively. The YAP/TAZ dual positive patients owned a worse TNM stage (P=0.015), poorer tissue differentiation (P=0.007), and a higher CA199 than those in negative patients. Multivariate Cox analysis identified that YAP/TAZ dual positivity as a significant factor predicted poorer OS (P=0.010) and DFS (P=0.028) in CCA patients after radical resection. In subgroup analysis, YAP/TAZ combination also significantly predicted OS (P=0.044) and DFS (P=0.043) in CCA patients with positive lymphatic metastasis and/or surgical margin who required adjuvant therapy. Conclusions: YAP/TAZ positivity is an independent predictive factor for survival in CCA patients after radical resectiony.

[Clinical significance of combined sST2 and NT-proBNP detection for the short-term prognosis of acute organophosphorus pesticide poisoning].

Objective: To explore the value of soluble growth stimulation expression gene 2 protein (soluble suppression of tumorigenicity 2; sST2) and N terminal B type brain natriuretic peptide (N-terminal probrainnatriuretic peptide, NT-proBNP) in evaluating the short-term prognosis of acute organophosphorus pesticide poisoning. Methods: select 228 patients with acute organophosphorus pesticide poisoning in our hospital from October 2017 to March 2020. According to the grade of poisoning degree, it was divided into 82 cases in mild and moderate group and 146 cases in severe group. hs-cTnI、CK-MB、sST2、NT-proBNP、APACHE Ⅱ score and cholinesterase activity were detected 4 h、12 h、24 h after admission. ROC curve was used to evaluate sST2 and NT-proBNP to predict the prognosis of AOPP. Results: 4 hours after admission, there was no significant difference in the scores of hs-cTnI, APACHE Ⅱ, cholinesterase and CK-MB between the Severe Group and the mild and moderate Group (P<0.05) . At 12 and 24 hours after admission, the scores of hs-cTnI, CK-MB and APACHE Ⅱ in severe group were higher than those in mild and moderate group, and the changes of Cholinesterase were more significant than those in 12 hours after Admission (P<0.05) . 4 hours after admission, SST2 and NT-proBNP levels were significantly higher in severe group than those in mild and moderate Group (P<0.05) . The level of SST2 and NT-proBNP in the severe group was significantly higher than that in the mild and moderate group 12 and 24 hours after Admission (P<0.01) , and the level of SST2 and NT-proBNP was significantly higher than that in the mild group 12 hours after Admission (P<0.05) . Correlation analysis showed that 24 hours after admission, sST2, NT-proBNP were positively correlated with APACHE-Ⅱ scores (R=0.634, 0.723, P<0.01) . The area under sST2 combined with NT-proBNP was 0.891, higher than that under sST2 and NT-proBNP at 12 h after admission. The 24 h APACHE Ⅱ score after admission area under the curve was 0.838. Conclusion: sST2 and NT-proBNP combined detection can early predict the occurrence of recent complications in AOPP patients.

Comparison of Isolation, Expansion and Cryopreservation Techniques to Produce Stem Cells from Human Exfoliated Deciduous Teeth (SHED) with Better Regenerative Potential.

Mesenchymal Stem Cells (MSCs) are adult stem cells that are gaining worldwide attention for their multi-potential use in tissue engineering-based regenerative medicine. They can be obtained from numerous sources and one of the excellent sources is the dental tissue, such as Stem cells that are extracted from the Human Exfoliated Deciduous teeth (SHED). SHED are considered ideal due to their inherent characteristics, including the capability to proliferate quickly with minimal oncogenesis risk, multipotency capacity and their ability to suppress the immune system. On top of these positive cell traits, SHED are easily accessible with the patient's safety assured, posing less ethical issues and could also provide a sufficient number of cells for prospective clinical uses. This is primarily attributed to their ability to differentiate into multiple cell linages, including osteoblasts, odontoblasts, neuronal cells, adipocytes, as well as endothelial cells. Albeit SHED having a bright future, there still remains an obstacle to develop reliable experimental techniques to retain the long-term regeneration potential of the stem cells for prospective research and clinical applications. Therefore, this review aims to describe the various isolation, expansion and cryopreservation techniques used by researchers in this stem cell field. Optimization of these techniques is crucial to obtain distinct SHED culture with preserved stem cell properties, which enable more reproducible results that will be the key for further stem cell therapy development.

MiR-222-5p promotes the growth and migration of trophoblasts by targeting AHNAK.

OBJECTIVE: The purpose of this study was to detect microRNA-222-5p (miR-222-5p) levels in placental tissues of preeclampsia (PE) pregnancies, and to explore the role of miR-222-5p in the proliferative and migratory potentials of trophoblast cell line HTR-8/SVneo. PATIENTS AND METHODS: Expression levels of miR-222-5p and AHNAK in placental tissues of PE pregnancies (n=24) and healthy pregnancies (n=24) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Potential influences of miR-222-5p and AHNAK on proliferative, migratory and apoptotic potentials in HTR-8/SVneo cells were examined. At last, Luciferase assay was conducted to illustrate the interaction between miR-222-5p and AHNAK in trophoblasts. RESULTS: It was found that miR-222-5p was downregulated in placental tissues of PE pregnancies. Overexpression of miR-222-5p stimulated proliferative and migratory potentials, and inhibited apoptosis in HTR-8/SVneo cells. Moreover, AHNAK was the target gene binding to miR-222-5p, and overexpression of AHNAK inhibited proliferative and migratory potentials and promoted apoptosis in HTR-8/SVneo cells. CONCLUSIONS: MiR-222-5p stimulates proliferative and migratory potentials and inhibits apoptosis in HTR-8/SVneo cells by negatively regulating AHNAK.

Abnormal expression of Rap2A as a prognostic marker for human breast cancer.

OBJECTIVE: The aim of this study was to explore the expression of GTPase protein Ras-related protein Rap-2a (Rap2A) in breast cancer (BC). Furthermore, the associations of Rap2A with clinicopathological parameters of BC patients were investigated. PATIENTS AND METHODS: quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine Rap2A expression in BC tissues and cells. The association between Rap2A expression and clinicopathological characteristics was analyzed by Chi-square test. Low expression of Rap2A in BC cells was conducted by transfection of small interfering RNA (siRNA). Subsequently, colony formation assay and transwell assay were used to detect the proliferation and invasion abilities of BC cells, respectively. RESULTS: Rap2A was highly expressed in both BC tissues and cells (p<0.05). Further analysis showed that tumor size, clinical stage, and distant metastasis were correlated with Rap2A expression (p<0.05). Besides, inhibition of Rap2A significantly decreased the proliferation and invasion abilities of BC cells (p<0.05). CONCLUSIONS: Rap2A acted as a promotor in the development of BC. Our findings suggested that Rap2A might be a new potential therapeutic target marker for BC treatment.

MiR-203 regulates proliferation and apoptosis of ovarian cancer cells by targeting SOCS3.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-203 regulates proliferation and apoptosis of ovarian cancer cells by targeting SOCS3, by H.-P. Liu, Y. Zhang, Z.-T. Liu, H. Qi, X.-M. Zheng, L.-H. Qi, J.-Y. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (21): 9286-9294-DOI: 10.26355/eurrev_201911_19421-PMID: 31773696" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19421.

Correlation between MRAS gene polymorphism and atherosclerosis.

OBJECTIVE: The aim of this study was to explore the correlation between muscle RAS oncogene homolog (MRAS) gene polymorphism and the onset risk of atherosclerosis (AS). PATIENTS AND METHODS: A total of 135 AS patients diagnosed and treated in our hospital from November 2017 to October 2018 were randomly enrolled in the observation group. Meanwhile, 150 healthy adults were selected as control group. Venous blood was withdrawn from all the subjects, and DNAs were extracted. MRAS gene loci rs9818870 and rs3755751 were analyzed by the multiplex SNaPshot method, and their correlations with the onset risk of AS were explored. RESULTS: No statistically significant differences in the frequencies at gene loci were observed between the two groups (p>0.05). Subjects with genotype TT at rs9818870 exhibited significantly higher risk of AS (p=0.041<0.05). The recessive model of rs9818870 (GG + AG/AA) in AS patients with coronary heart disease was correlated with AS (p=0.048<0.05). Similarly, the dominant model of rs3755751 (TT/TC+CC) in those with hypertension was associated with AS (p=0.027<0.05). CONCLUSIONS: MRAS gene is correlated with the onset of AS to a certain degree.

[Predictive value of early detection of hs-cTnI and sST2 for secondary cardiac damage in severe acute organophosphorus pesticide poisoning].

Objective: To investigate the value of high-sensitivity cardiac troponin I (hs-cTnI) and soluble suppression of tumorigenicity 2 (sST2) in predicting cardiac complications of severe acute organophosphorus pesticide poisoning (SAOPP) . Methods: All 274 SAOPP patients from September 2014 to February 2019 were selected. According to the results of hs-cTnI detection, the patients were divided into non-elevated troponin group (78 cases) and troponin elevation group (196 cases) at 1 hour after admission. 3 days after admission, there were 109 cases of complication and 165 cases of non-complication according to the presence or absence of cardiac complications. The changes of hs-cTnI, sST2, N-terminal B-type brain natriuretic peptide (NT proBNP) , acute physiology and chronic health (APACHE-Ⅱ) , cholinesterase activity, left ventricular ejection fraction (LVEF) , short axis shortening rate (FS) were observed and analyzed. The predictive value of hs-cTnI and sST2 were evaluated by receiver operating characteristic curve (ROC) analysis. Results: The sST2 level in patients with troponin elevation group was significantly higher than that in non-elevated troponin group (P<0.05) . Compared with the non-complication and non-elevated troponin group, the patients with non-complication and troponin elevation group had elevated hs-cTnI, sST2 and decreased cholinesterase (P<0.05) . Compared with other groups, the hs-cTnI, sST2, NT-proBNP, and APACHE-Ⅱ scores in the complication and troponin elevation group were significantly increased, and cholinesterase was significantly reduced (P<0.05) . In the non-complication group, LVEF and FS were in the normal range, and there was no significant difference between the groups (P>0.05) . Compared with other groups, the LVEF and FS of patients with elevated troponin in the complications group were significantly decreased (P<0.05) . Correlation analysis showed that hs-cTnI and sST2 were positively correlated in patients with SAOPP complications (r=0.725, P<0.01) . hs-cTnI, sST2 and APACHE-Ⅱ scores were positively correlated in the complications group (r=0.846, 0.885, P<0.01) . ROC results showed that the areas under the curve for predicting SAOPP secondary heart damage of hs-cTnI (1 hour after admission) and sST2 (3 days after admission) were 0.945 and 0.833, respectively. Conclusion: hs-cTnI and sST2 may have important clinical value in the early diagnosis and prognosis evaluation of patients with SAOPP secondary cardiac damage.

[Clinical analysis of surgical treatment of post-infarction left ventricular aneurysm: a series of 254 patients].

Objective: To examine the efficacy of two surgical procedures on post-infarction left ventricular aneurysm. Methods: The clinic data of 254 patients with post-infarction left ventricular aneurysm, who underwent surgical ventricular reconstruction between January 1997 and December 2019 in Department of Cardiovascular Surgery, Nanjing Hospital Affiliated to Nanjing Medical University was analyzed retrospectively. There were 183 males and 71 females aged from 31 to 81 years, with a median age of 64.6 years. Based on the size of the ventricular aneurysm, there were 73 patient received linear reconstruction (linear group) and 181 patients received endoventricular patch plasty technique (patch plasty group). Ejection fraction, left ventricular systolic and end diastolic volume and left ventricular systolic and end diastolic volume index were recorded preoperatively, 2-week, 3-month, 1-year and 5-year after operation. The survival curves were plotted with Kaplan-Meier method and the survival rates were compared by Log-rank test. Results: All patients underwent surgery with a mean cardiopulmonay bypass duration of (92±32) minutes (44 to 196 minutes) and aortic cross clamp duration of (67±22) minutes (33 to 152 minutes).There were 9 perioperative deaths with a mortality rate of 3.5%. Angina pectoris of other cases are relief and heart function improved greatly. Five years after operation, the percentage of cardiac function (New Yord Heart Association) class Ⅲ to Ⅳ patients decreased from 96.1%(244/254) to 9.9%(16/161). There was no significant difference in survival rate between linear group and patch plasty group at 1-, 3-, 5-years postoperatively (96%, 91%, 77% vs. 96%, 90%, 79%, P=0.562). Ejection fraction increased from (39±10)% (range: 22% to 50%) preoperatively to (46±6)% (range: 39% to 54%) 1-year postoperatively in the linear group, while increased from (38±13)% (range: 26% to 51%) preoperatively to (50±6)% (range: 39% to 55%) in the patch plasty group. Conclusions: Left ventricular reconstruction is quite effective for patients with post-infarction left ventricular aneurysm. The choice of operative approaches is determined by the size and range of ventricular aneurysm. Both linear reconstruction and endoventricular patch plasty technique can got similarly surgical outcomes with near and late curative effect.

Partial thyroxine-binding globulin deficiency in a family with coding region mutations in the TBG gene.

PURPOSE: T4-binding globulin (TBG) is the main thyroid hormone (TH) transporter present in human serum. Inherited thyroxine-binding globulin (TBG) deficiency is caused by mutations in the TBG (SERPINA7) gene, which is located on the X chromosome. This study was performed to report and evaluate coding region mutations in TBG gene for partial thyroxine-binding globulin deficiency. METHODS: A pedigree spanning four generations is described in this study. The proband is a female with partial TBG deficiency. All members of this pedigree underwent thyroid function tests, while Sanger sequencing was used to identify the TBG gene mutations. Bioinformatics databases were used to evaluate the deleterious effects of the mutation(s). Two hundred and seven unrelated individuals were used to evaluate the thyroid function of individuals with different TBG mutations. A one-way ANOVA was used to analyze the impact of the TBG mutations on thyroid function. RESULTS: TBG gene sequencing results revealed that the proband had a novel mutation in codon 27 leading to alanine to valine substitution (p.A27V). This mutation was associated with lower serum T4 levels (p < 0.0001) when compared to the groups that did not carry the mutation. The previously reported p.L283F mutation was also found in the proband. The hemizygous p.L283F individuals presenting with lower T4 serum and TBG levels (p < 0.001) when compared to wildtype males and females. Both mutations were deleterious upon SIFT and PolyPhen-2 evaluation. CONCLUSION: Associated with partial thyroxine-binding globulin deficiency, this study reports a novel p.A27V mutation in the TBG gene.