5 signature genes revealed by single-cell profiling identified unique immune subtypes affecting the prognosis of ovarian cancer.

OBJECTIVE: Ovarian cancer (OC) ranks among the most prevalent gynecological malignancies, with surgery, chemotherapy, and immunotherapy constituting primary treatment modalities. However, despite advancements, immunotherapy, particularly immune checkpoint inhibitors, has yielded suboptimal outcomes. The pressing need to identify biomarkers predictive of clinical prognosis underscores our objective. We aim to discern gene signatures and establish prognostic subgroups, specifically in the context of immunotherapy and chemotherapy, guiding clinical decision-making. MATERIALS AND METHODS: We used the Tumor Immunotherapy Gene Expression Resource (TIGER) and The Cancer Genome Atlas (TCGA) databases to extract signature genes of prognostic significance. Unsupervised consensus clustering was employed to classify patients based on these signature genes. The Tumor Immune Estimation Resource (TIMER) database, along with the R packages "maftools" and "ESTIMATE" facilitated immune infiltration estimation. Gene set variation analysis (GSVA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were implemented to probe immune-related cell signaling pathways among distinct subtypes. The Tumor Immune Dysfunction and Exclusion (TIDE) database was used to assess immunotherapy effects, while the R package "OncoPredict" evaluated drug sensitivity differences among subtypes. RESULTS: We identified five prognostically influential genes in ovarian cancer: IGFBP7, JCHAIN, CCDC80, VSIG4, and MS4A1. Utilizing these signature genes, we categorized TCGA-OV patients into five clusters, each associated with varying clinical prognoses. Notably, 2 clusters exhibited superior prognoses, accompanied by enhanced immune cell infiltration. KEGG enrichment analysis revealed their heightened enrichment in cellular immunity and immune cell interaction pathways. Given the elevated expression levels of multiple immune checkpoint molecules, these clusters may substantially benefit from immune checkpoint inhibitor therapy. Additionally, chemotherapy sensitivity analysis indicated their favorable responses to first or second-line chemotherapy regimens. CONCLUSIONS: We subclustered ovarian cancer patients by 5 signature genes obtained from the Single-cell RNA sequencing (scRNA-seq) dataset, which demonstrated a good typing effect. Patients in the two molecular subtypes showed better survival, higher immune cell infiltration, and higher drug sensitivity. This meticulous typing may help clinicians to quickly assess the prognosis of patients and the response to immunotherapy and chemotherapy.

[Application of next-generation sequencing technology detecting ctDNA in the diagnosis and treatment of gastric cancer].

Gastric cancer is a malignant tumor with high morbidity and mortality, which is a serious threat to human life and health. At present, the diagnosis and course monitoring of gastric cancer mainly rely on gastroscopic biopsy and CT, but their invasiveness and delay limit their clinical value. Gastric cancer patients urgently need a real-time, accurate, non-invasive diagnosis and course monitoring method. Circulating tumor DNA(ctDNA) is single or double stranded DNA released into body fluid by tumor cells, which contains the same genetic mutations as the original tumor cells. It is also one of the newly emerged biological markers. With the emergence and development of next-generation sequencing(NGS) technology, the sensitivity and specificity of ctDNA detection continue to increase, and it is gradually becoming a new choice for tumor diagnosis and disease course monitoring. In this paper, the current application of the next-generation sequencing technology detecting ctDNA in diagnosis and treatment of gastric cancer was discussed.

[Research advances in epithelial - mesenchymal transition in hepatocellular carcinoma].

Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their own features and become mesenchymal cells, and more and more studies have shown that EMT plays an important role in the invasion and metastasis of hepatocellular carcinoma (HCC). This article reviews the signaling pathways involved in the progression of HCC and molecules involved in the regulation of EMT, in order to provide a new direction for the treatment of HCC.

Effects of pressure and temperature on the carrier transports in organic crystal: a first-principles study.

By employing density-functional theory coupled with Holstein-Peierls model, we investigate the pressure and temperature dependence of the hole and electron mobilities in naphthalene single crystal from atmospheric pressure up to 2.1 GPa (at room temperature) and from 5 to 296 K (at ambient pressure). It is found that the pressure reduces the electron-phonon coupling strength and enhances the mobilities. Importantly, we point out that only when temperature-dependent structure modifications are taken into account can one better describe the temperature-dependent transport behavior. Especially, the band to hopping crossover transition temperature for the electron transport in the c'-axis is calculated to be around 153 K, which is close to the experimental result of between 100 and 150 K. If this temperature-dependent structure modifications were neglected, the transition temperature would be only about 23 K, as previously obtained [L. J. Wang et al., J. Chem. Phys. 127, 044506 (2007)].

Roles of inter- and intramolecular vibrations and band-hopping crossover in the charge transport in naphthalene crystal.

We calculate the hole and electron mobilities in naphthalene crystal from 10 to 300 K within the framework of the Holstein-Peierls model coupled with first-principles density-functional-theory-projected tight-binding band structures. All the electron-phonon coupling constants, including both local and nonlocal parts for inter- and intramolecular vibrations, have been taken into considerations through density functional theory. The band-hopping crossover transition temperature for the electron transport in the c' axis is calculated to be around 23 K. We have identified a few high frequency intramolecular vibrations which are very important to the charge transport in naphthalene crystal due to their comparatively large electron-phonon coupling constants. However, their contributions to the temperature dependence of mobility are minor because of the small phonon occupations and small nonlocal coupling strengths. The low frequency intermolecular modes (longitudinal optical modes) are found to be the major contributions to the temperature dependent charge transfer properties in naphthalene crystal. Even though the calculated qualitative temperature dependence is in agreement with experiment, the predicted absolute mobility is about one to two orders of magnitude larger.

Proteins in fluid from the proximal vas deferens of normal fertile and vasectomized men.

Fluids were collected from the proximal vas deferens of 18 normal fertile men and 32 vasectomized men during vasectomy or vasovasostomy, respectively, and the protein concentration and pattern of proteins were then analysed by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE). In normal fertile men and vasectomized men there were no significant differences in total protein concentrations between fluids from the left and right vas deferens. The total protein concentration of proximal vas fluid from vasectomized men (82.8 +/- 7.5 mg/ml; mean +/- SEM) was significantly higher than in normal fertile men (36.8 +/- 4.5 mg/ml). In vasectomized men there was no significant correlation between the total protein concentration in vas fluid and the duration of vasectomy. The patterns of protein bands in proximal vas fluid differed from those in seminal plasma. There was no relationship between the pattern of protein bands in vas fluid and the duration of vasectomy. Five major groups of proteins from proximal vas fluid were identified and no new major proteins were found in proximal vas fluid were identified and no new major proteins were found in proximal vas fluid after vasectomy. The percentage of 80K and 67K protein bands in vasectomized men was higher than that in normal fertile men. It is suggested that, after vasectomy, the physiological environment of the proximal vas deferens may be changed. One of these changes may be the higher total protein concentration (especially the 80K and 67K proteins) in vas fluid.

PIP: Fluids were collected from the proximal vas deferens of 18 normal fertile men and 32 vasectomized men during vasectomy or vasovasostomy, respectively, and the protein concentration and pattern of proteins were then analyzed by sodium dodecylsulphate polyacrylamide gel electrophoresis. The subjects were 18 normal, fertile men 22-33 years old, who had 2 or more children and volunteered for vasectomy, and 32 vasectomized men 25-40 years old, who asked for vasovasostomy because of the death of 1 or more of their children since their vasectomy 1-8 years prior. The physical examination was normal. Testicular size was normal as measured by the Prader's orchidometer (15-20 ml). Vasectomy and vasovasostomy were performed under local anaesthesia using procaine hydrochloride. In normal, fertile men and vasectomized men there were no significant differences in total protein concentration between fluids from the left and the right vas deferens. In vasectomized men the total protein concentration in vas fluid (82.8 +or- 7.5 mg/ml, n = 37; mean +or- SEM) was significantly higher than in normal fertile men (36.8 +or- 4.5 mg/ml, n = 21) in all samples (p 0.001), irrespective of whether samples were from the left (p 0.02) or the right vas (p 0.002). In vasectomized men there were no significant correlations between the concentration of total protein and the duration of vasectomy (p 0.05). The vas fluids from 14 (left and right samples) fertile men and from 21 vasectomized men were electrophoresed. The same protein pattern was found in 12 samples for fertile men and in 19 samples for vasectomized men. The patterns of protein bands in proximal vas fluid differed from those in seminal plasma. Five major groups of proteins from proximal vas fluid were identified and no new major proteins were found in proximal vas fluid after vasectomy. After vasectomy the physiological environment of the proximal vas deferens may be changed with the result of higher total protein concentration (especially the 80K and 67K proteins) in vas fluid.

Analysis of spermatozoa from the proximal vas deferens of vasectomized men.

This study assessed the condition of spermatozoa from the proximal vas deferens of men after vasectomy. The fluids of both proximal vas deferens were collected from 67 vasectomized men by cannulating the vas deferens at the time of vasectomy reversal. Selected sperm parameters were analysed after incubation of the spermatozoa for 30 min at 37 degrees C. Sperm concentration in the proximal vas from vasectomized men (16,312 +/- 21,496 million per ml, geometric mean: 7948 +/- 398 million per ml) was significantly higher than that of fertile men and was maintained at a constant level independent of the duration of vas obstruction. The means of sperm motility (36.2 +/- 26.2%), spermatozoa with normal morphology (50.7 +/- 21.7%), sperm viability (53.0 +/- 25.3%) and hypo-osmotic swelling test (HOS-test, 53.9 +/- 21.7%) were statistically lower than the respective values for normal fertile men. There was no significant correlation between the duration of vas obstruction and the above semen parameters. In 46.4% of vas fluids all spermatozoa were immotile and this condition was more common after 3 years of vasectomy. Immotile spermatozoa in the proximal vas fluids at the time of vasectomy reversal may be an important factor for predicting semen quality and fertilizing ability after vasovasostomy. There were no significant differences in the results of sperm-cervical mucus penetration test (CMPT) between spermatozoa from vasectomized and fertile men. Antisperm antibodies on the surface of spermatozoa from the vas of vasectomized men were determined by the immunobead test (IBT; 78.6% for IgG, 32.1% for IgA) and sperm cervical mucus contact test (SCMC, 36.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: Vasectomy is a widely used birth control method. Although spermatogenesis continues in the testis after vasectomy, the secretion and absorption functions of the epididymis and proximal vas deferens are changed. Spermatozoa stored in the epididymis may therefore be affected. Some men regret having been sterilized and seek to reverse their vasectomy. While the development of microsurgery has increased the success rate of vasovasostomy, the rate at which such men are able to impregnate fertile women remains only in the 50-58% range. Defects of spermatozoa in the epididymis following vasectomization may contribute to this low fertilizing capacity of men who have attempted to reverse the effects of their vasectomy. This study assessed the condition of spermatozoa from the proximal vas deferens of 67 men after vasectomy. Subjects were aged 25-40 years with duration of vasectomy three months to ten years with no chronic medical illnesses. The men's fluids were collected from both proximal vas deferens by cannulating the vas deferens at the time of vasectomy reversal. Selected sperm parameters were then analyzed after incubation of the spermatozoa for 30 minutes at 37 degrees Celsius. Sperm concentration in the proximal vas from vasectomized men was significantly higher than that of fertile men and was maintained at a constant level independent of the duration of vas obstruction. The means of sperm motility, spermatozoa with morphology, sperm viability, and hypo-osmotic swelling test were statistically lower than the respective values for normally fertile men, while no significant correlation was observed between the duration of vas obstruction and the above semen parameters. In 46.4% of vas fluids all spermatozoa were immotile, especially after three years of vasectomy, suggesting that immotile spermatozoa in the proximal vas fluids at the time of vasectomy reversal may be an important factor for predicting semen quality and fertilizing ability after vasovasostomy. There were not, however, significant differences in the results of sperm-cervical mucus penetration test between spermatozoa from vasectomized and fertile men. It is noted that the presence of antisperm bodies on the spermatozoa from the vas of vasectomized men, as determined by the immunobead test, may partially explain the lower pregnancy rate after vasovasostomy, with spermatozoa parameters potentially closely reflecting those in the cauda epididymis after vasectomy.

Analysis of spermatozoa from the proximal vas deferens of fertile men.

Fluids from the left and right proximal vas deferens were collected from 105 normal fertile men by cannulating the vas deferens during vasectomy, and sperm parameters analysed. Sperm motility (73.1 +/- 13.3%), normal sperm morphology (75.2 +/- 11.1%), sperm viability (72.7 +/- 18.8%) and the hypo-osmotic swelling test (73.3 +/- 19.2%) were in the normal range, compared with that of ejaculated spermatozoa. However, sperm concentration in the proximal vas deferens (6274.6 +/- 5103.8 x 10(6) ml-1 was higher than that in semen. Sperm concentration in the right vas deferens was significantly higher (P < 0.05) than that in the left and the percentage of spermatozoa showing abnormal cervical mucus penetration was significantly higher (47%) for the left than for the right (18%). There were no anti-sperm antibodies on the surface of spermatozoa from the vas deferens as determined by the sperm cervical mucus contact test and immunobead test. These parameters of spermatozoa from the proximal vas may reflect those of spermatozoa from the human cauda epididymis.

Congenital absence of vas deferens treated by artificial spermatocele constructed from the tunica vaginalis; report of six cases.

Six patients with congenital absence of the vas deferens were treated by artificial spermatoceles (ASCs) in an attempt to collect sperm for subsequent artificial insemination (AI). The ASC was constructed from a flap of tunica vaginalis from the patient. Sperm were aspirated from the ASC each month; there was wide variation in the concentration of sperm recovered [33.0 +/- 48.2 x 10(6) mL-1 (range 0.1-200)] and motility and normal morphology of the sperm were 19.0 +/- 17.9% and 48.8 +/- 23.4% respectively. Although a total of 14 cycles of AI was performed using the aspirated sperm, pregnancy did not result. Both poor sperm recovery and poor motility contributed to this failure. The condition of the epididymis observed during scrotum examination is reported. It is suggested that in some patients with congenital absence of vas deferens, the paired Wolffian ducts may differ from each other in their development.