Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

Objective:To evaluate the short-term and long-term outcomes of patients with locally advanced low rectal cancer who achieved clinical complete response (cCR) or near-clinical complete response (near-cCR) after neoadjuvant chemoradiotherapy (nCRT) and then underwent local excision.Methods:This was a descriptive case series study. Clinical data of patients with low rectal cancer who received neoadjuvant therapy, achieved cCR or near-cCR, underwent local excision, and had complete postoperative follow-up data were retrospectively analyzed. The study period was from May, 2015 to October, 2024, and the patients were treated at Fujian Medical University Union Hospital. Indications for local excision in this study were as follows: pathologically confirmed rectal adenocarcinoma, with the lower edge of the tumor ≤ 6 cm from the anal verge; maximum diameter of the lesion ≤ 2 cm after nCRT; no regional lymph node metastasis detected by transrectal endoscopic ultrasound (ERUS), pelvic magnetic resonance imaging (MRI), or positron emission tomography-computed tomography (PET-CT) after nCRT; MRI showing fibrosis of the primary lesion with a small amount of high signal on diffusion-weighted imaging (DWI), consistent with ymrT0-1 stage; serum carcinoembryonic antigen level within the normal range (< 5 μg/L) after nCRT; complicated with severe underlying diseases such as cardiovascular and cerebrovascular diseases and assessed as unable to tolerate radical surgery through comprehensive evaluation; and signed informed consent for local excision. The contraindications were: colonoscopic pathology indicating poorly differentiated adenocarcinoma or signet ring cell carcinoma; suspected lateral lymph node metastasis before neoadjuvant therapy; patients with residual lesions exceeding 3 cm in range after treatment. A total of 153 patients were included in this study, including 84 males and 69 females. The median age was 62 years, and the median distance from the tumor to the anal verge after neoadjuvant therapy was 4.0 cm. The short-term efficacy indicators of this study included postoperative complications of local excision and postoperative pathological results, and the long-term efficacy indicators included oncological prognosis (3-year cumulative local recurrence rate, 3-year cumulative distant metastasis rate, 3-year progression-free survival, and 3-year overall survival) and anal function at 1 year after surgery evaluated using the Low Anterior Resection Syndrome (LARS) scale where the total score is 42 points such that 0-20 points indicate no LARS, 21-29 points indicate mild LARS, and 30-42 points indicate severe LARS.Results:Postoperative pathology showed 122 cases (79.7%) of ypT0 stage, 10 cases (6.5%) of ypT1 stage, 18 cases (11.8%) of ypT2 stage, and 3 cases (2.0%) of ypT3 stage. The incidence of surgery-related complications was 42.5% (65/153), and the main complications included perianal pain (39.9%, 61/153), intestinal wall incision dehiscence (21.6%, 33/153), and intestinal wall incision infection (18.3%, 28/153). The proportion of patients who received hypofractionated radiotherapy before surgery and developed intestinal wall incision dehiscence was 65.2% (15/23), which was higher than that in the conventional long-course (13.6%, 16/118) and short-course radiotherapy groups (16.7%,2/12) (χ 2=30.55, P<0.001); of the 20 patients who received additional immunotherapy before surgery, 13 developed intestinal wall incision dehiscence was 65.0%, which was higher than that in the group without additional immunotherapy [15.0%(20/133),χ 2=25.66, P<0.001]. The median follow-up time of the entire group was 35.4 months. During the follow-up period, there were 9 cases of postoperative local recurrence, with a 3-year cumulative local recurrence rate of 7.9% and 5 cases of distant metastasis, with a 3-year cumulative distant metastasis rate of 5.0%. The 3-year progression-free survival rate was 89.0%, and the 3-year overall survival rate was 95.9%. At 1 year after surgery, 10 cases (10.5%, 10/95) had severe anal dysfunction, and the median LARS score of the entire group was 5.0 (range: 0-41.0) points. Conclusions:For patients with locally advanced low rectal cancer who achieve cCR or near-cCR after neoadjuvant therapy, local excision results in favorable oncological prognosis and anal function preservation effects; however, the incidence of complications is relatively high.

Objective:To evaluate the short-term and long-term outcomes of patients with locally advanced low rectal cancer who achieved clinical complete response (cCR) or near-clinical complete response (near-cCR) after neoadjuvant chemoradiotherapy (nCRT) and then underwent local excision.Methods:This was a descriptive case series study. Clinical data of patients with low rectal cancer who received neoadjuvant therapy, achieved cCR or near-cCR, underwent local excision, and had complete postoperative follow-up data were retrospectively analyzed. The study period was from May, 2015 to October, 2024, and the patients were treated at Fujian Medical University Union Hospital. Indications for local excision in this study were as follows: pathologically confirmed rectal adenocarcinoma, with the lower edge of the tumor ≤ 6 cm from the anal verge; maximum diameter of the lesion ≤ 2 cm after nCRT; no regional lymph node metastasis detected by transrectal endoscopic ultrasound (ERUS), pelvic magnetic resonance imaging (MRI), or positron emission tomography-computed tomography (PET-CT) after nCRT; MRI showing fibrosis of the primary lesion with a small amount of high signal on diffusion-weighted imaging (DWI), consistent with ymrT0-1 stage; serum carcinoembryonic antigen level within the normal range (< 5 μg/L) after nCRT; complicated with severe underlying diseases such as cardiovascular and cerebrovascular diseases and assessed as unable to tolerate radical surgery through comprehensive evaluation; and signed informed consent for local excision. The contraindications were: colonoscopic pathology indicating poorly differentiated adenocarcinoma or signet ring cell carcinoma; suspected lateral lymph node metastasis before neoadjuvant therapy; patients with residual lesions exceeding 3 cm in range after treatment. A total of 153 patients were included in this study, including 84 males and 69 females. The median age was 62 years, and the median distance from the tumor to the anal verge after neoadjuvant therapy was 4.0 cm. The short-term efficacy indicators of this study included postoperative complications of local excision and postoperative pathological results, and the long-term efficacy indicators included oncological prognosis (3-year cumulative local recurrence rate, 3-year cumulative distant metastasis rate, 3-year progression-free survival, and 3-year overall survival) and anal function at 1 year after surgery evaluated using the Low Anterior Resection Syndrome (LARS) scale where the total score is 42 points such that 0-20 points indicate no LARS, 21-29 points indicate mild LARS, and 30-42 points indicate severe LARS.Results:Postoperative pathology showed 122 cases (79.7%) of ypT0 stage, 10 cases (6.5%) of ypT1 stage, 18 cases (11.8%) of ypT2 stage, and 3 cases (2.0%) of ypT3 stage. The incidence of surgery-related complications was 42.5% (65/153), and the main complications included perianal pain (39.9%, 61/153), intestinal wall incision dehiscence (21.6%, 33/153), and intestinal wall incision infection (18.3%, 28/153). The proportion of patients who received hypofractionated radiotherapy before surgery and developed intestinal wall incision dehiscence was 65.2% (15/23), which was higher than that in the conventional long-course (13.6%, 16/118) and short-course radiotherapy groups (16.7%,2/12) (χ 2=30.55, P<0.001); of the 20 patients who received additional immunotherapy before surgery, 13 developed intestinal wall incision dehiscence was 65.0%, which was higher than that in the group without additional immunotherapy [15.0%(20/133),χ 2=25.66, P<0.001]. The median follow-up time of the entire group was 35.4 months. During the follow-up period, there were 9 cases of postoperative local recurrence, with a 3-year cumulative local recurrence rate of 7.9% and 5 cases of distant metastasis, with a 3-year cumulative distant metastasis rate of 5.0%. The 3-year progression-free survival rate was 89.0%, and the 3-year overall survival rate was 95.9%. At 1 year after surgery, 10 cases (10.5%, 10/95) had severe anal dysfunction, and the median LARS score of the entire group was 5.0 (range: 0-41.0) points. Conclusions:For patients with locally advanced low rectal cancer who achieve cCR or near-cCR after neoadjuvant therapy, local excision results in favorable oncological prognosis and anal function preservation effects; however, the incidence of complications is relatively high.

Objective By establishing finite element model of the proximal femur, the injury risk of proximal femur under the conditions of self-selected speed rise and rapid rise at initial stage of standing during sit-to-stand (STS) transition was analyzed.Methods CT images of proximal femur in the elderly were processed with three-dimensional (3D) reconstruction and reverse modeling, so as to complete the solid model. The finite element model was established through material assignment and meshing. Based on the finite element analysis software ANSYS, the boundary conditions were constrained, and 1.733 kN and 1.837 kN loads were applied to obtain stress distributions and strain of proximal femur at different rising speeds. Results The stress concentrated at medial edge of the greater trochanter and the femoral neck. The peak stress and micro-strain appeared on inner edge of the larger rotor. The peak stress was 30.16 MPa and peak micro-strain was 2 553.5 at rapid rising speed. The peak stress and peak micro-strain at self-selected rising speed were 28.69 MPa and 2 430.4, respectively, which were relatively lower. For stress concentration area of femoral neck, the stress ranges at rapid rising speed and self-selected rising speed were 13.42-23.46 MPa and 12.76-25.51 MPa, respectively.Conclusions Frequent STS transition may increase the risk of fatigue fractures for proximal femur in the elderly. Rapid STS transition has a higher injury risk for proximal femur than STS transition at self-selected speed.

Objective To analyze the use of antibiotics in perioperative period of cesarean section,and to summarize the experience of scientific intervention to promote rational drug use.Method 192 cesarean section included in the study were inpatients in December 2015 to December 2016 in our hospital,were grouped according to the order of admission,divided into control group(95 cases)and observation group(97 cases),were given routine perioperative antibiotic treatment.The observation group was treated with scientific medication intervention,and the control group was not intervened.The two groups of white blood cell count,postoperative body temperature and hospitalization time were counted,the infection types and infection rate were counted,and the treatment costs of the two groups were counted.Results The white blood cell count of the observation group was significantly higher than the control group,postoperative body temperature recovery time and hospitalization time was significantly shorter than the control group,the difference was significant(P<0.05); after two groups appeared infection phenomenon,including urinary tract infection,incision infection and puerperal infection as well as intrauterine infection,and two groups in different types of infection and the infection rate by comparison there was no statistically significant difference; statistical analysis and comparison of treatment related costs of the two groups of patients,to observe antibacterial drug group,the total cost of expenses and hospitalization costs were significantly lower than that of the control group,and patients with antimicrobial drugs accounted for the total proportion of drugs were significantly lower than the control group,the difference was statistically significant(P<0.05).Conclusion Cesarean section perioperative use of antibiotics in the process,through the implementation of scientific intervention can obtain ideal effect,promote rational and normative clinical medication,reduce hospitalization expenses and antimicrobial drug costs,promote the recovery of patients after surgery,and does not increase the infection after operation.

The rules of acupoint selection for diabetic peripheral neuropathy (DPN) based on data mining technology are analyzed. Literature regarding acupuncture for DPN published in core journals from January of 2005 to December of 2014 was retrieved in CNKI database and Wanfang database to establish a database of acupuncture prescriptions, which were included into the TCM Inheritance Platform software (Version 2.0). The data mining methods, including rule analysis, revised mutual information, etc. were applied to analyze the acupuncture prescriptions and the frequency of each acupoint was calculated. The results indicated Zusanli (ST 36), Sanyinjiao (SP 6), Quchi (LI 11), Yanglingquan (GB 34), Hegu (LI 4), Shenshu (BL 23), etc. were mostly selected in acupuncture for DPN; in addition, 19 acupoint combinations were acquired. It is concluded that acupuncture for DPN applied reinforcing methods as main rules, accompanied with promoting blood andcirculation; the acupoint selection focused onmeridians and back-points.

Objective To explore body mass index(BMI),glucose and lipid metabolism status of high -nor-mal blood pressure that selected Uygur,Kazak and Han nationalities in parts of Xinjiang.Methods Some representa-tive regions were selected,including Fuhai County of Altay,Xinyuan County of Yili,Yanqi County of Korla and Pasto-ral of Urumqi South Mountain in August 2012 -2014 August,each region was randomly selected two survey points respectively,400 -450 people were expected to conduct on -site investigations in every survey point,and 1 046 cases were collected containing Uygur,Kazak and Han nationalities who were conformed to diagnostic standard,206 cases in which the Kazak (115 men and 91 women),Han 518 cases (277 men and 241 women),322 cases of Uygur (174 men and 148 women).in order to realize the BMI,waistline,lipid metabolism and fasting glucose status.Results (1)BMI was descending:Kazak >Uygur >Han,between the three groups respectively were statistically significant differences[(26.07 ±3.23)kg/m2 ,(25.85 ±4.09)kg/m2 ,(24.63 ±3.00)kg/m2 ,F =19.829,P <0.05],sub-group analyzes:BMI for men descending:Kazak >Uygur >Han,comparison between groups of Han,Uygur and Kazak provided results which were statistically significant(F =6.752,P <0.05);but statistical significance merely existed in Han and Kazak female comparison(F =2.248,P <0.05).Waist comparison showed a decreasing sequence:Uygur>Kazak >Han,there were no statistically significant difference between every three groups[(86.32 ±8.63)cm, (85.50 ±10.11)cm,(84.06 ±7.57)cm,F =1.675,P >0.05],gender comparison was found the same characteristics. (2)Blood fat comparison between different ethnic:Descending order of serum TG:Kazak >Han >Uygur,comparison among groups of Han,Uygur and Kazak differences were statistically significant(F =5.829,P <0.05),comparison among groups of Han,Uygur and Kazak differences were statistically significant(F =5.829,P <0.05).Comparison of Serum TC:Han >Uygur >Kazak.Statistical significance indwelled in Han,Uygur and Kazak comparison (F =5.298, P <0.05);The result of comparing serum HDL -C,LDL -C in different ethnic groups:there was no statistically significant difference between different group (F =1.026,0.744,all P >0.05).Descending order was presenting in fasting glucose:Han >Uygur >Kazak.Statistical significance appears in Han,Uygur and Kazak comparison (F =8.989,P <0.05).Conclusion High -normal blood pressure of Uygur,Kazak and Han nationalities who appeared glucose metabolic disorders,BMI and waistline increase(overweight and obesity),combined with the characteristics of different national regional life,it is of great significance to prevent and delay the occurrence of hypertension through strengthening the management and intervention of high -normal blood pressure crowd,giving medical care to the people suffering from overweight,obesity,and glucose metabolic disorders,and making full preparation for the primary of hypertension.

Objective:To study the expression of caveolin-1 in colorectal adenocarcinoma tissues and its correlation with microlymphatic vessel density (LMVD), and to investigate the clinical pathological prognostic significance of caveolin-1 and LMVD in patients with colorectal cancer.Methods:The expression of caveolin-1 and LMVD in 45 specimens of normal colorectal tissues, and 90 specimens of colorectal adenocarcinoma tissues were detected by immunohistochemistry technique. The correlation between their expression and the clinicopathologic features was analyzed. Muhivariable Cox regression was used to analyze the association between the laboratory indices and overall survival time.Results:The positive rates of caveolin-1 in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues (P<0.01). LMVD in colorectal adenocarcinoma tissues were significantly higher than those in normal colorectal tissues (P<0.01). Mean LMVD in group with caveolin-1 positive was significantly higher than in that with caveolin-1 negative. The median survival time was 26.7 months. Cox regression analysis showed that the caveolin-1 expression, invation depth, lymph nodemetastasis, TNM stage, liver metastasis and LMVD were independent risk factors of overall survival time of patients with colorectal carcinoma. Conclusions:Caveolin-1 may contribute to the lymphangiogenesis in the tumor. During the occurrence and development of colorectal adenocarcinoma, there is a close relationship between the expression of caveolin-1 and lymphatic microvessel of tumor. Caveolin-1 expression and microlymphatic vessel density are significant prognostic value of colorectal carcinoma.

Objective To explore the effect of anti-terrorism practices on the psychological health of military policemen.Methods The health statement of 101 soldiers and officers who took part in the anti-terrorism practices was estimated with Zung Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS).ResultsThe total raw score, positive titles average score and negative titles score of SAS of these military policemen were all higher than national norm ( PP<0.05). The total raw score and standrad score of SDS were also higher than national norm, but without statistical meaning( P>0.05); while, the scores of hopelessness and impractical life feeling were significantly lower than national norm ( P<0.01), the scores of apptite decreasing, the weight lighten, easy tired were significantly higher than national norm ( P<0.01).ConclusionThe military policemen have higher anxietical feeling and some level of somatizational depression.