Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.

Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

Objective:To explore the effects of Yishen Tonglong Granules (YSTLG) on cell proliferation and apoptosis in a nude mouse model of androgen independent prostate cancer subcutaneous transplantation based on non classical Wnt signaling pathway.Methods:The tumor-bearing nude mouse model was established using the human prostate cancer bone metastatic cell line PC-3. After successful modeling, the mice were equally divided into six groups using the random number table method: model group, Western medicine group, Chinese materia medica low-, medium-, and high-dosage groups, and Chinese materia medica-Western medicine combination group. Corresponding drug interventions were administered to each group. Following 28 consecutive days of drug administration, the nude mice were euthanized. Tumor tissues were harvested for pathological observation via HE staining. Cell proliferation was assessed by immunohistochemistry; apoptosis was detected using TUNEL assay; the expressions of non-canonical Wnt signaling pathway-related proteins (Wnt5a, Rac1, RhoA, NFATc1) were analyzed through Western blot and immunohistochemical methods.Results:THE staining results demonstrated that YSTLG could effectively ameliorate pathological alterations in tumor tissues. Compared with the model group, the Chinese materia medica low-, medium-, and high-dosage groups, as well as the Chinese materia medica-Western medicine combination group, exhibited reduced proliferation indices ( P<0.01), elevated apoptosis indices ( P<0.01), down-regulated protein expressions of Wnt5a, Rac1, RhoA, and NFATc1 ( P<0.01), and decreased optical density values of Wnt5a, Rac1, RhoA, and NFATc1 ( P<0.01). These effects displayed a dosage-dependent trend. The Chinese materia medica-Western medicine combination group achieved the most pronounced therapeutic outcomes. Conclusions:YSTLG may exert inhibitory effects on the proliferation of androgen-independent prostate cancer cells and promote apoptosis, possibly through suppression of the non-canonical Wnt signaling pathway. Furthermore, its combination with Wnt signaling inhibitors may exhibit synergistic therapeutic effects.

Objective To examine the impact of arid climates on distribution of Oncomelania hupensis snails in the Poyang Lake area, so as to provide insights into precision control of O. hupensis snails in the Poyang Lake area. Methods O. hupensis snails-infested grass islands in Hukou County, Lianxi District and Lushan City in the northern Poyang Lake area, and Jinxian County, Nanchang County and Poyang County in the southern Poyang Lake area were selected as the study areas, and the occurrence of frames with living snails and the mean density of living snails were captured from snail surveys in the study areas in spring and autumn each year from 2006 to 2023. Five years 2007, 2011, 2013, 2019 and 2022 were selected as drought years, and the mean daily water levels were collected at the Xingzi hydrological station in the drought years, normal flow year (2012) and flood year (2020). The numbers of days with water levels ranging from the lower elevation (11 m) to the upper elevation (16 m) for snail survival and the numbers of days with water levels of 11 m and below were collected in the Poyang Lake area, and the changes of snail indicators were compared in different grass islands in the Poyang Lake area before and after drought. Results The numbers of days with water levels ranging from 11 to 16 m were 110, 88, 136 d and 125 d at the Xingzi hydrological station in four drought years 2007, 2011, 2013 and 2019, which were less than in the flow year and flood year, and the days with water levels of 11 m and below were 242, 277, 220 d and 198 d in four drought years 2007, 2011, 2013 and 2019, which were longer than in the flow year and flood year. A total of 416 snails-infested marshlands were surveyed in the Poyang Lake area from 2006 to 2021, and the survey marshlands accounted for 43.12% (307/712) and 46.98% (109/232) of total marshlands in the southern and northern Poyang Lake areas, respectively. The median occurrence of frames with living snails and mean density of living snails were 0.60% (interquartile range, 4.04%) and 0.010 1 snail/0.1 m² (interquartile range, 0.076 1 snail/0.1 m²) in drought years, which were both lower than those [1.33% (5.19%) and 0.022 8 (0.098 9) snail/0.1 m²] in non-drought years (χ²= 42.170 and 44.911, both P values < 0.01). The proportion of grass islands with a continuous decline in snail indicators was higher in the southern Poyang Lake area than in the northern Poyang Lake area after the next year of drought (24.24% vs. 2.33%; χ² = 10.633, P < 0.01), and the proportion of grass islands with rebounding snail indicators was higher in the northern Poyang Lake area than in the southern Poyang Lake area (53.49% vs. 15.76%; χ² = 26.966, P < 0.01). A longitudinal analysis of snail indicators in marshlands with rebounding snail indicators after drought showed 1 to 5 years for return to pre-drought snail status, with a median of 2 (interquartile range, 1) years, and snail status was more likely to rebound if the occurrence of frames with living snails and the mean density of living snails were 2.11% and 0.025 5 snail/0.1 m² and greater in snails-infested grass islands. Conclusions Drought causes a remarkable decline in O. hupensis snail indicators in the Poyang Lake area, with a more remarkable impact in the southern Poyang Lake area, and 1 to 5 years are required for return to pre-drought snail status.

Objective To evaluate the effect of acupuncture at Yin Wei point on postoperative nausea and vomiting(PONV)in female patients undergoing abdominal surgery.The clinical efficacy of postoperative nausea and vomiting(PONV)and its impact on gut microbiota.Methods This study included 184 patients who underwent gynecological laparoscopic surgery in Jinhua Central Hospital from January 2021 to April 2024.They were randomly divided into control group(n=93)and acupuncture group(n=91)using a random number method.At the completion of surgery,the control group received intravenous injection of 5mg of tropisetron hydrochloride.In acupuncture group,on the basis of control group,intervention was performed by needling the palmar Yin Wei points of both forearms for 30 minutes before surgery.The incidence and severity of PONV were compared between two groups of patients.In addition,fecal samples were collected from two groups of patients before and after surgery,and differential analysis of gut microbiota community structure was performed using 16S amplicon absolute quantitative sequencing technology.Results In the 0-24 hours after surgery,40 cases of the acupuncture group and 56 cases of control group experienced PONV.The acupuncture group's PONV incidence was lower than control group's(P＜0.05).The nausea severity of acupuncture group after surgery was significantly lower than that of control groups.The proportion of patients taking antiemetic drugs after surgery in acupuncture group was also significantly lower than that in control group(P＜0.05).Before surgery,the two groups have no significant difference regarding Chao1,ACE,Shannon,and Simpson indices(P＞0.05).After surgery,the acupuncture group's Chao1,ACE,and Shannon indices were significantly higher than control group's(P＜0.05).The Simpson scores of two groups of patients were compared after surgery,and no significant difference was found(P＞0.05).The Observed,Chao1,ACE,and Shannon indices were significantly higher in the acupuncture group after surgery than before(P＜0.05).The incidence of adverse reactions in acupuncture group and control group were 8.8％and 8.6％,respectively,and there was no statistical significance(P＞0.05).Conclusion Acupuncture at Yin Wei point combined with intravenous injection of tropisetron can reduce the incidence of PONV in patients undergoing gynecological laparoscopic surgery.

Colorectal cancer is currently one of the most common malignant tumors in the world,and its incidence and mortality rates have gradually increased in recent years.As insidious symptoms characterize early colorectal cancer,most of the patients have already developed into late or advanced stages in the primary survey.For stage Ⅳ metastatic colorectal cancer(mCRC),surgery supplemented with chemotherapy or radiotherapy for mCRC patients has a low 5-year survival rate.With the development of immunology in recent years,PD-1/PD-L1 inhibitors have made breakthroughs in treating malignant tumors.They also have improved the therapeutic efficacy of some mCRC patients,especially those with microsatellite instability-high/mismatch repair deficient.The guidelines recommend this approach.However,patients with microsatellite stable/mismatch repair proficiency,which accounts for more than 90%,are poorly treated with PD-1/PD-L1 inhibitors.Fortunately,there are several clinical studies that reported that some of this type of mCRC can gain some benefit.In this review,we examined the anti-tumor mechanism of PD-1/PD-L1 inhibitors and the latest progress of PD-1/PD-L1 inhibitor's clinical application in patients of mCRC with different genotypes.We discussed the prospect of PD-1/PD-L1 inhibitor combination therapy to provide a reference to the benefit of this type of patients and provide information for optimizing the dosing regimen of PD-1/PD-L1 inhibitors in the treatment of mCRC.

Objective To explore the clinical value of preoperative Glasgow-Blatchford score(GBS)and AIMS65 score in predicting the prognosis of patients with non-variceal upper gastrointestinal bleeding after receiving interventional treatment.Methods The clinical data of 59 patients with non-variceal upper gastrointestinal bleeding,who received transcatheter arterial embolization(TAE)at the Department of Interventional Vascular Surgery,Shanghai Tenth People's Hospital of China between 2018 and 2021,were collected.The clinical value of GBS and AIMS65 score in predicting patient's outcome was analyzed.Results With the preoperative GBS and AIMS65 scores increasing,the mortality also increased.Compared with AIMS65 score(AUC=0.630,0.95％CI:0.494-0.752),GBS(AUC=0.823,95％CI:0.702-0.910)had a higher predictive value for postoperative in-hospital death in patients with non-variceal upper gastrointestinal bleeding after receiving interventional treatment.With a GBS cutoff＞9 points,the Youden index for predicting in-hospital death was 0.54.Conclusion In predicting the postoperative in-hospital death for patients with non-variceal upper gastrointestinal bleeding after receiving TAE,the clinical value of the preoperative GBS score is higher than that of AIMS65 score.

Objective:To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization.Methods:The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed.Results:(1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm 3 and cone size <2 cm 3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference ( P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm ( RR=3.084, 95% CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm 3 and those with cone size ≥2 cm 3 ( RR=1.700, 95% CI: 0.935-3.092; P=0.077). Conclusion:The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.