Neuroendocrine carcinoma of the endometrium: a retrospective analysis of data from a single center.

BACKGROUND: Neuroendocrine carcinoma (NEC) originating from the endometrium is rare, and there is limited knowledge regarding its diagnosis and optimal management. In this study, we present our experience with 11 patients with endometrial NEC, aiming to provide guidance for clinical practice. METHODS: We retrospectively collected the clinical, pathological, and treatment data of 11 patients with endometrial NEC who were treated at the First Affiliated Hospital of Zhengzhou University from January 2011 to July 2023. The clinicopathological characteristics, treatment and prognosis of these patients were analyzed. RESULTS: The median age of the patients was 55.0 (39.0-64.0) years, and the median tumor size was 40.0 (33.0-60.0) mm. Irregular vaginal bleeding was the most common symptom observed in 10 out of 11 patients, while metabolic syndrome occurred in only 2 out of 11 patients. Six out of the 11 patients were diagnosed at an early stage. Among the patients, 6 were diagnosed with endometrial NECs, while the remaining patients had a combination of endometrial NEC and other non-NEC endometrial carcinomas. All patients underwent surgery, except for one who received only chemotherapy due to multiple metastases. After surgery, adjuvant chemotherapy was administered to 5 patients, chemotherapy combined with radiotherapy was given to 3 patients, and 2 patients did not receive any adjuvant therapy. A total of 10 patients completed the follow-up, with a median follow-up time of 51.0 (14.3-81.0) months. Unfortunately, 2 patients died from the disease. CONCLUSION: NECs originating from the endometrium might not be affected by metabolic disorders. Preoperative diagnosis of these tumors was challenging. The primary approach for managing endometrial NEC can be multimodal treatment centered around surgery.

Quantitative proteomics analysis in small cell carcinoma of cervix reveals novel therapeutic targets.

BACKGROUND: As a rare pathologic subtype, small cell carcinoma of the cervix (SCCC) is characterized by extensive aggressiveness and resistance to current therapies. To date, our knowledge of SCCC origin and progression is limited and sometimes even controversial. Herein, we explored the whole-protein expression profiles in a panel of SCCC cases, aiming to provide more evidence for the precise diagnosis and targeting therapy. METHODS: Eighteen SCCC samples and six matched normal cervix tissues were collected from January 2013 to December 2017. Data independent acquisition mass spectrometry (DIA) was performed to discriminate the different proteins (DEPs) associated with SCCC. The expression of CDN2A and SYP in corresponding SCCC tissues was verified using immunohistochemistry. GO and KEGG enrichment analyses were used to identify the key DEPs related to SCCC development and tumor recurrence. RESULTS: As a result, 1311 DEPs were identified in SCCC tissues (780 up-regulated and 531 down-regulated). In up-regulated DEPs, both GO analysis and KEGG analysis showed the most enriched were related to DNA replication (including nuclear DNA replication, DNA-dependent DNA replication, and cell cycle DNA replication), indicating the prosperous proliferation in SCCC. As for the down-regulated DEPs, GO analysis showed that the most enriched functions were associated with extracellular matrix collagen-containing extracellular matrix. KEGG analysis revealed that the DEPs were enriched in Complement and coagulation cascades, proteoglycans in cancer, and focal adhesion-related pathways. Down-regulation of these proteins could enhance the mobility of cancer cells and establish a favorable microenvironment for tumor metastasis, which might be accounted for the frequent local and distant metastasis in SCCC. Surprisingly, the blood vessels and circulatory system exhibit a down-regulation in SCCC, which might be partly responsible for its resistance to anti-angiogenic regimens. In the stratification analysis of early-stage tumors, a group of enzymes involved in the cancer metabolism was discriminated in these recurrence cases. CONCLUSIONS: Using quantitative proteomics analysis, we first reported the whole-protein expression profiles in SCCC. Significant alterations were found in proteins associated with the enhancement of DNA replication and cellular motility. Besides the association with mitosis, a unique metabolic feature was detected in cases with tumor recurrence. These findings provided novel targets for disease surveillance and treatments, which warranted further validation in the future.

Separation of five flavone glycosides including two groups with similar polarities from Dracocephalum tanguticum by a combination of three high-speed counter-current chromatography modes.

The separation of compounds with similar polarities is challenging. In the present study, five flavone glycosides, including two groups with similar polarities, were obtained from Dracocephalum tanguticum by three high-speed counter-current chromatography modes, including flow rate conversion mode, recycling mode, and heart-cut mode. With flow rate conversion mode, compounds 3 and 4 with similar polarities and compound 5 were separated by high-speed counter-current chromatography with ethyl acetate/methanol/water (5.0% acetic acid) (8:2:10, v/v) system. The flow rate was controlled as: 1.8 mL/min for 0-160 min, 2.2 mL/min for 160-200 min, and 2.5 mL/min for 200-400 min. However, compounds 1 and 2 with similar polarities were not separated due to the similar distributive properties. Then, a recycling and heart-cut mode were introduced to improve the separation efficiency. The heart-cut mode was introduced in the second and third cycles, and compounds 1 and 2 were well separated in the fourth cycle. Consequently, five flavone glycosides, including two groups with similar polarities were obtained and identified as cosmosiin (1), pedaliin (2), quercetin-3-O-rutinoside (3), pedaliin-6''-acetate (4), and sorbifolin-6-O-ß-glucopyranoside (5). The current strategy provides a reference for separating compounds with similar polarities from a crude sample.

Low preoperative serum ALB level is independently associated with poor overall survival in endometrial cancer patients.

Aim: To reveal the prognostic significance of serum albumin (ALB) concentration in endometrial cancer (EC) patients in China. Patients & methods: 345 EC patients were enrolled in a single center, and the preoperative serum ALB concentration were measured. Kaplan-Meier curve analysis and Cox proportional hazards regression model were performed to evaluate the associations between ALB concentration and overall survival (OS) of EC patients. Results: The EC patients with lower preoperative serum ALB concentration exhibited a significantly poorer OS (p < 0.05). Univariate analysis and multivariate analysis indicated that serum ALB concentration was an independent prognostic factor of unfavorable OS for EC patients. Conclusion: Our results showing that ALB concentration may serve as an independent prognostic factor for EC patients.

Separation of five flavonoids with similar polarity from Caragana korshinskii Kom. by preparative high speed counter-current chromatography with recycling and heart cut mode.

Five flavonoids with similar polarity were obtained from Caragana korshinskii Kom. by preparative high speed counter-current chromatography. Due to their similar polarity, it is difficult to select a suitable solvent system for one-step separation. Three fractions including one pure compound were only obtained with a relatively suitable solvent system of ethyl acetate: n-butanol:water (0.5% glacial acetic acid) (4:6:10, v:v:v). In order to improve the separation efficiency, recycling and heart cut modes were introduced. As a result, two flavonoids with separation factor value at 1.13 and the other two with separation factor value at 1.20 were successfully separated. Finally, five flavonoids with purity higher than 98% were obtained. Fortunately, a new compound named myricetin 3'-methyl ether 3-O-glucoside-7-O-rhamnoside was obtained. The results indicated that the recycling combined with heart-cut mode could be effective for the preparation of natural compounds with similar polarity.

[Genetic diagnosis for a patient with Leydig cell hypoplasia caused by two novel variants of LHCGR gene].

OBJECTIVE: To explore the genetic basis for a patient with Leydig cell hypoplasia. METHODS: Whole exome sequencing was used to detect genetic variants in the patient. Suspect variants were verified by PCR and Sanger sequencing of the family members. RESULTS: The patient was found to carry two novel variants, namely c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala), of the luteinizing hormone receptor gene (LHCGR), where were respectively inherited from her father and mother. Upon prenatal diagnosis, the fetus was found to be a heterozygous carrier of the c.265A>T (p.Ile189Leu) variant. CONCLUSION: The compound heterozygous variants of c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala) of the LHCGR gene probably underlie the Leydig cell hypoplasia in the patient.

LncRNA LINC01305 silencing inhibits cell epithelial-mesenchymal transition in cervical cancer by inhibiting TNXB-mediated PI3K/Akt signalling pathway.

Cervical cancer (CC) remains one of the leading malignancies afflicting females worldwide, with its aetiology associated with long-term papillomavirus infection. Recent studies have shifted their focus and research attention to the relationship between long non-coding RNAs (lncRNAs) and CC therapeutic. Thus, the aim of the current study was to investigate the underlying mechanism of lncRNA LINC01305 on the cell invasion, migration and epithelial-mesenchymal transition (EMT) of CC cells via modulation of the PI3K/Akt signalling pathway by targeting tenascin-X B (TNXB). The expressions of LINC01305, TNXB, MMP2, MMP9, E-cadherin, vimentin, PI3K, Akt, p-PI3K, p-Akt and TNXB were detected in this study. After which, the cell invasion and migration abilities of the CC cells were determined respectively. Bioinformatics and the application of a dual luciferase reporter gene assay provided verification indicating that TNXB is the target gene of lncRNA LINC01305. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis methods revealed that the expressions of MMP2, MMP9, vimentin, PI3K, Akt, p-PI3K and p-Akt were decreased following the down-regulation of LncRNA LINC01305 or overexpression of TNXB. LncRNA LINC01305 silencing or TNXB overexpression was noted to decrease the migration and invasion of SiHa cells. Taken together, the key findings of the current study present evidence suggesting that lncRNA LINC01305 silencing suppresses EMT, invasion and migration via repressing the PI3K/Akt signalling pathway by means of targeting TNXB in CC cells, which ultimately provides novel insight and identification of potential therapeutic targets for CC.

[The value of chest X-ray and cervical vascular ultrasound in predicting the presence of non-recurrent laryngeal nerves].

OBJECTIVE: To determine the value of chest X-ray and cervical vascular ultrasound in predicting the presence of non-recurrent laryngeal nerves (NRLN) in patients with thyroid disorders. METHODS: Preoperative, intraoperative and postoperative documents of 2 251 patients with various thyroid disorders between January 2006 and December 2013 were reviewed. All of the patients underwent preoperative chest X-ray examinations. The patients who had confirmed NRLN during surgery were given a cervical vascular ultrasound examination postoperatively. RESULTS: A total of 49 patients (2. 18%, A group) were identified having NRLN by preoperative chest X-ray as they showed aberrant right subclavian artery (ARSA). Of those suspected cases of NRLN, 23 (46.94%) were confirmed during subsequent surgeries and no NRLN injury was inflicted. In the 2 202 unsuspected cases (B group), 5 (0. 23%) were discovered having NRLN during surgeries, and one (20. 00%) NRLN injury occurred. ARSA were found in postoperative cervical vascular ultrasound examination in all of the 28 cases of NRLN confirmed during surgeries. The postoperative cervical vascular ultrasound suggested a normal right subclavian artery (RSA) for the 26 chest X-ray revealed but surgically dismissed cases of NRLN. The 23 X-ray predicted NRLN were revealed more quickly in surgeries than those that had been failed to show in X-ray (t= -18. 867 2, P=O. 000 0). CONCLUSION: Chest X-ray of patients scheduled for thyroid surgery should be reviewed carefully and cervical vascular ultrasound should be allied for predicting ARSA before surgery. Detection of ARSA can accurately predict the existence of NRLN, preventing NRLN injury and shorten the duration of subsequent operations.

Lacticaseibacillus casei IB1 Alleviates DSS-Induced Inflammatory Bowel Disease by Regulating the Microbiota and Restoring the Intestinal Epithelial Barrier.

Inflammatory bowel disease (IBD) is becoming an increasingly serious health problem in humans and animals. Probiotics can inhibit the development of IBD. Due to the specificity of the strains, the function and mechanism of action of different strains are still unclear. Here, a DSS-induced colitis mouse model was utilized to investigate the ability and mechanism by which Lacticaseibacillus casei IB1 alleviates colitis. Treatment with L. casei IB1 improved DSS-induced colitis in mice, as indicated by increased body weight, colon length, and goblet cell numbers and decreased disease activity index (DAI), proinflammatory factor (TNF-α, IL-1ß, and IL-6) levels, and histopathological scores after intake of IB1. IB1 supplementation also improved the expression of tight junction proteins and inhibited the activation of the MAPK and NF-κB signaling pathways to alleviate intestinal inflammation. In addition, IB1 rebalanced the intestinal microbial composition of colitis mice by increasing the abundance of Faecalibaculum and Alistipes and decreasing the abundance of Bacteroides and Escherichia_Shigella. In summary, L. casei IB1 showed great potential for relieving colitis by regulating the microbiota and restoring the epithelial barrier. It can be used as a potential probiotic for the prevention and treatment of UC in the future.

Efficacy of PD-1/PD-L1 blockade immunotherapy in recurrent/metastatic high-grade neuroendocrine carcinoma of the cervix: A retrospective study.

Although high-grade neuroendocrine carcinoma of the cervix (HGNECC) accounts for less than 1 % of all cervical cancers, it exhibits marked aggressiveness and resistance to radiation and chemotherapy. We retrospectively investigated the efficacy of immunotherapy for recurrent/metastatic HGNECC in a real-world setting. From September 2016 to December 2022, a total of 29 patients with HGNECC accepted PD-1/PD-L1 inhibitors; of these, six cases (20.7 %) were PD-L1 positive (combined positive score ≥1). According to their primary treatment, the patients were assigned to either a surgery group (n = 14) or a non-surgery group (n = 15). In the surgery group, four patients received anti-PD-1 therapy immediately after surgery, while six, two, one, and one patients started immunotherapy after the first, second, third, and forth recurrence, respectively. In the non-surgery group, seven patients started immunotherapy as part of their primary treatment, while the other four, two, and two patients received anti-PD-1 drugs as the second, third, and forth lines of treatment, respectively. The seven-patient group showed longer progression-free survival after immunotherapy (PFSi) and overall survival than those of their counterparts (P = 0.085 and 0.08, respectively), while this benefit was not observed in other subgroups. No significant correlation was observed between PD-L1 and PFSi expression. Interestingly, one patient with a high tumor mutation burden (TMB-H) had a long PFSi of 26 months and experienced no recurrence until the last follow-up. Based on these findings, we propose that PD-1/PD-L1 inhibitors may prolong the survival of patients with HGNECC who start immunotherapy as the first-line of treatment. This indicates that early immunotherapy may be a better choice for this challenging malignancy. Moreover, the predictive role of TMB-H in immunotherapeutic outcomes requires further investigation.