BRCA2, PALB2, RECQL4 Germline Pathogenic Variants, and Somatic TP53 Mutation in Triple Metachronous Malignancies: A Case Report and Literature Review.

Background: Multiple primary cancer (MPC) refers to the presence of more than one cancer in an individual. Triple primary malignancies are uncommon. Case: We report the case of a 50-year-old postmenopausal woman in our gynecology department, diagnosed with endometrial cancer, ovarian cancer, and unilateral breast cancer. She carried germline mutations in BRCA2, PALB2, and RECQL4, along with a somatic pathogenic variant in TP53. Endometrial cancer patients harboring germline pathogenic variants in BRCA2 exhibit a heightened risk of ovarian and breast cancer. BRCA2 is known to play a role in the development of ovarian and breast cancer, while PALB2 is identified as a gene associated with breast cancer susceptibility. RECQL4 has been linked to breast cancer, cervical cancer, and other tumors. Conclusion: Genetic testing may be imperative for identifying MPC in endometrial cancer patients. For individuals with BRCA2 and other gene pathogenic variants, routine examination and monitoring of the endometrium, ovaries, breasts, and other sites prone to polygenic cancer are recommended.

[Pollution Characteristics and Risk Assessment of Nitrated Polycyclic Aromatic Hydrocarbons in the Atmosphere of Guangdong-Hong Kong-Macao Greater Bay Area].

To investigate the pollution characteristics and sources of nitrated polycyclic aromatic hydrocarbons (NPAHs) in Guangdong-Hong Kong-Macao Greater Bay Area (GBA), 44 ambient air samples were collected using the active sampling method, which were then determined via gas chromatography-triple quadrupole tandem mass spectrometry. The main results showed that filters, polyurethane foam, and XAD-2 resin were the essential materials for sampling NPAHs in ambient air in order to characterize the pollution status accurately. The levels of ρ(Σ18NPAHs) in ambient air at GBA ranged from 162 pg·m-3 to 2094 pg·m-3, and the average levels of ρ(Σ18NPAHs) were (675±430) pg·m-3 in summer and (637±349) pg·m-3 in winter. NPAHs were widely found in the ambient air of GBA and were dominated by 1-nitronaphthalene (220 pg·m-3), 2-nitronaphthalene (146 pg·m-3), 9-nitroanthracene (105 pg·m-3), and 2-nitrofluoranthene (72 pg·m-3). The congener profile characteristics of NPAHs in summer and winter were similar. The gas/particle partitioning characteristics of NPAHs revealed that dicyclic and tricyclic NPAHs tend to occur in the gas phase, and tetracyclic NPAHs tend to be adsorbed in the particle phase. The fraction of NPAHs concentrations in the particulate fraction of their total atmospheric concentrations increased with the increase in their molecular weight. In winter, NPAHs tend to be adsorbed in the particle phase, whereas in summer, NPAHs tend to exist in the gas phase. Based on the ratios of characteristic pollutants, in both the summer and winter season, photochemical reactions were the main source of NPAHs in the atmosphere of GBA and were primarily generated by the reaction of the hydroxyl radical in the daytime. The carcinogenic risk value calculation showed that the current carcinogenic risk of NPAHs in the ambient air of GBA was controllable.

Ruxolitinib exerts neuroprotection via repressing ferroptosis in a mouse model of traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Various forms of cells death are involved in the pathological process of TBI, without exception to ferroptosis, which is mainly triggered by iron-dependent lipid peroxidation. Although there have been studies on ferroptosis and TBI, the effect of ruxolitinib (Ruxo), one type of FDA approved drugs for treating myelofibrosis, on the process of ferroptosis post-TBI is remained non-elucidated. Therefore, using a controlled cortical impact device to establish the mouse TBI model, we examined the effect of Ruxo on TBI-induced ferroptosis, in which the inhibitor of ferroptosis, Ferrostatin-1 (Fer-1) was used as a positive control. Moreover, we also respectively explored the effects of these two interventions on neurological deficits caused by TBI. We firstly examined the expression patterns of ferroptosis-related markers at protein level at different time points after TBI. And based on the expression changes of these markers, we chose 12 h post-TBI to prove the effect of Ruxo on ferroptosis. Importantly, we found the intensely inhibitory effect of Ruxo on ferroptosis, which is in parallel with the results obtained after Fer-1-treatment. In addition, these two treatments both alleviated the content of brain water and degree of neurodegeneration in the acute phase of TBI. Finally, we further confirmed the neuroprotective effect of Ruxo or Fer-1 via the wire-grip test, Morris water maze and open field test, respectively. Thereafter, the lesion volume and iron deposition were also measured to certificate their effects on the long-term outcomes of TBI. Our results ultimately demonstrate that inhibiting ferroptosis exerts neuroprotection, and this is another neuroprotective mechanism of Ruxo on TBI.

[Effects of Direct Moxibustion of "Ganshu"(BL 18) on the Contents of T cells in Peripheral Blood in Rats with Precancerous Lesion of Primary Hepatocellular Carcinoma].

OBJECTIVE: To observe the effect of moxibustion stimulation of "Ganshu"(BL 18) region on contents of T cells in the peripheral blood in rats with Diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC), so as to explore its effective in improving immunoregulatory function. METHODS: Seventy male Wistar rats were randomly divided into control group (n=10), model group(n=15), direct moxibustion-15 s group(n=15), direct moxibustion-30 s group (n=15) and ginger-separated moxibustion group(n=15). The primary HCC precancerous lesion model was established by intraperitoneal injection of DEN (50 mg/kg), once every 3 days for 10 weeks. Moxibustion was applied to bilateral "Ganshu"(BL 18) for about 15 min (3 moxa-cones), or 30 min (six moxa-cones), with or without ginger-slice separation, once every other day for 10 consecutive weeks. The contents of T cells of CD 3+, CD 4+, CD 8+ and CD 4+/CD 8+ ratio in the peripheral blood were detected with Flow Cytometey(FCM), pathological changes of liver were observed by light microscope after hematoxylin-eosin(HE) stain. RESULTS: Compared to the control group, the contents of blood CD 3+ and CD 4+ T cells and ratio of CD 4+/CD 8+ were significantly down-regulated, while that of CD 8+T cells was obviously increased in the model group(P<0.05,P<0.01). After moxibustion intervention, the decreased CD 3+ and CD 4+T cells and CD 4+/CD 8+ levels and the increased CD 8+T cell contents were reversed in all the 3 moxibustion groups (P<0.05, P<0.01), except CD 3+ in the ginger-separated moxibustion group (P>0.05). There were no significant differences among the three moxibustion groups in the CD 3+, CD 4+, CD 8+ and CD 4+/CD 8+ levels (P>0.05). In addition, the pathological changes of liver tissue as central vein deviation or absence, disordered arrangement of hepatic cords, narrowing of the hepatic sinusoid, hyperplasia of collagen fibers, formation of tuberosis, unevenness of liver cells with nuclear anachromasis and higher heteromorphism, and macronucleus oncocytes in primary HCC rats were not observed or milder after moxibustion intervention. CONCLUSIONS: Direct moxibustion and ginger-separated moxibustion can improve pathological changes of hepatic cells in rats with HCC, which may be associated with its actions in raising blood CD 3+ and CD 4+ T cell contents and reducing CD 8+ T levels to improve immune function.

[Effects of acupuncture stimulation of different acupoint groups on sleeping latency, serum and hippocampal TNF-α and IL-25 contents in rats with gastric mucosal injury].

OBJECTIVE: To observe the effect of acupuncture intervention on gastric ulcer (GU) and sleeping quality from the viewpoint of brain-gut axis which plays an important role in the regulation of many vital functions in the body. METHODS: Forty male Wistar rats were randomized into normal control, GU model, acupuncture of "Zhongwan"(CV 12)-"Zusanli"(ST 36, gastric function regulating acupoints), acupuncture of "Shenmai" (BL 62)-"Zhaohai" (KI 6, sleep-promotion acupoints), and acupuncture of CV 12-ST 36+ BL 62-KI 6 (combined treatment) groups, with 8 rats in each group. GU model was established by intragastric perfusion of dehydrated alcohol (1 mL/rat), and sleep model established by intraperitoneal injection of pentobarbital sodium (40 mg/kg) after the last treatment. The abovementioned acupoints were punctured with filiform needles and stimulated by manipulating the needle for about 30 s, once every 5 min during 20 min of needle retention. The treatment was conducted once daily for five days. The contents of tumor necrosis factor-alpha (TNF-α) and interleukin-25(IL-25) in the serum and hippocampal tissues were detected by ELISA. RESULTS: Compared with the normal control group, the gastric ulcer index score, barbiturate-induced sleeping time, and TNF-α and IL-25 contents in both serum and hippocampus were significantly increased in the model group (P < 0.01). Following acupuncture treatment, in comparison with the model group, the gastric ulcer index score, barbiturate-induced sleeping time, and TNF-α and IL-25 contents in both serum and hippocampus were significantly down-regulated in the CV 12-ST 36, BL 62-KI 6 and combined treatment groups (P < 0.01, P < 0.05). The effects of the CV 12-ST 36 and combined treatment groups were remarkably superior to those of the BL 62-KI 6 group in down-regulating ulcer index score, serum IL-25, and hippocampal TNF-α and IL-25 contents (P < 0.01, P < 0.05). In addition, the effects of the BL 62-KI 6 and combined treatment groups was considerably better than that of the CV 12-ST 36 group in shortening barbiturate-induced sleeping time (P < 0.01, P < 0.05). The effect of the combined treatment group was markedly better than that of the CV 12-ST 36 and BL 62-KI 6 groups in lowering serum TNF-α content (P < 0.05). CONCLUSION: Acupuncture stimulation of CV 12, ST 36, KI 6 and BL 62 can relieve the gastric mucosal lesion, and shorten barbiturate-induced sleeping time in gastric ulcer rats, which may be related to its effects in reducing TNF-α and IL-25 contents in the serum and hippocampus tissues, suggesting a correlation between the gastrointestinal disorder and sleeping.