Phellinus linteus activates Treg cells via FAK to promote M2 macrophage polarization in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor worldwide. Within HCC's tumor microenvironment, focal adhesion kinase (FAK) plays a critical role. Regulatory T cells (Treg) modulate the polarization of tumor-associated macrophages , but the relationship between FAK, Treg cells, and macrophages remains underexplored. Phellinus linteus (PL) shows promise as a treatment for HCC due to its pharmacological effects. This study aimed to explore the relationship between FAK and Treg-macrophages and to assess whether PL could exert a protective effect through the FAK process in HCC. Initially, C57BL/6-FAK-/- tumor-bearing mice were utilized to demonstrate that FAK stimulates HCC tumor development. High dosages (200 µM) of FAK and the FAK activator ZINC40099027 led to an increase in Treg (CD4+CD25+) cells, a decrease in M1 macrophages (F4/80+CD16/32+, IL-12, IL-2, iNOS), and an increase in M2 macrophages (F4/80+CD206+, IL-4, IL-10, Arg1, TGF-ß1). Additionally, FAK was found to encourage cell proliferation, migration, invasion, and epithelial-mesenchymal transition while inhibiting apoptosis in HepG2 and SMMC7721 cells. These effects were mediated by the PI3K/AKT1/Janus Kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase (p38 MAPK)/Jun N-terminal Kinase (JNK) signaling pathways. Furthermore, PL exhibited a potent antitumor effect in vivo in a dose-dependent manner, reducing FAK, Treg cells, and M2 macrophages, while increasing M1 macrophages. This effect was achieved through the inhibition of the PI3K/AKT/JAK/STAT3, and p38/JNK pathways. Overall, our findings suggest that FAK promotes HCC via Treg cells that polarize macrophages toward the M2 type through specific signaling pathways. PL, acting through FAK, could be a protective therapy against HCC.

Characteristics and scoring method of computed tomography in open-globe injuries.

BACKGROUND: Open-globe injuries (OGIs) remain the important cause of visual impairment and loss in all ages. Computed Tomography (CT) is a useful and common tool in the evaluation of the injuries of the eyeball. Prognostic value of CT scan in OGIs has been evaluated in many studies. However, there is no published consistent systematic scoring method for CT scan in OGIs. The purpose of this study was to evaluate the CT characteristics of OGIs and build a scoring method according to the CT scans which may aid the clinicians in management of OGIs. METHODS: Retrospective chart review of inpatients with clinical diagnosis of OGIs between 2017 and 2021 at Department of Ophthalmology, Henan Eye Institute, Henan Eye Hospital, Henan provincial People's Hospital (Zhengzhou, China). RESULTS: There were 1120 eyes from 1117 patients included in our study. The mean age was 35.7 ± 21.9 years with the range from 1 to 91 years. Significant male predominance was noted (889, 79.6%). CT scans of the OGIs were evaluated. Abnormality of anterior segment, posterior segment, and globe contour and volume were graded respectively. The most serious abnormality of anterior segment, posterior segment, and globe contour and volume were grade 3, 4 and 3 respectively and score 3, 4 and 3 respectively. Score of the CT scans of an open-injured globe ranged from 0 to 10. The correlation coefficient between the score and wound length was 0.798. The correlation coefficient between the score and final visual acuity was 0.799. In 78 eyes with 0 score, 70 eyes (89.7%) gained final visual acuity of 0.3 or better. In 31 eyes with 10 score, 20 eyes (64.5%) underwent evisceration of the eye globe and 10 eyes got visual acuity of no light perception and 1 eye lost to follow-up. CONCLUSIONS: CT scans is a useful tool in evaluating the severity of an open-injured globe. Scoring of the CT scans of an open-injured globe is a meaningful attempt and it may provide useful prognostic information regarding the outcome of an open-injured globe.

Safflower Yellow Inhibits Progression of Hepatocellular Carcinoma by Modulating Immunological Tolerance via FAK Pathway.

OBJECTIVE: To explore the anti-tumor effect of safflower yellow (SY) against hepatocellular carcinoma (HCC) and the underlying potential mechanism. METHODS: An in vitro model was established by mixing Luc-Hepa1-6 cells and CD3+CD8+ T cells, followed by adding programmed cell death protein 1 (PD-1) antibody (Anti-mPD-1) with or without SY. The apoptosis was detected by flow cytometry and the level of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. The protein levels of programmed cell death 1 ligand 1 (PD-L1), chemokine ligand (CCL5), C-X-C motif chemokine ligand 10 (CXCL10) were measured by Western blot. An in situ animal model was established in mice followed by treatment with anti-mPD-1 with or without SY. Bioluminescence imaging was monitored with an AniView 100 imaging system. To establish the FAK-overexpressed Luc-Hepa1-6 cells, cells were transfected with adenovirus containing pcDNA3.1-FAK for 48 h. RESULTS: The fluorescence intensity, apoptotic rate, release of inflammatory cytokines, and CCL5/CXCL10 secretion were dramatically facilitated by anti-mPD-1 (P<0.01), accompanied by an inactivation of PD-1/PD-L1 axis, which were extremely further enhanced by SY (P<0.05 or P<0.01). Increased fluorescence intensity, elevated percentage of CD3+CD8+ T cells, facilitated release of inflammatory cytokines, inactivated PD-1/PD-L1 axis, and increased CCL5/CXCL10 secretion were observed in Anti-mPD-1 treated mice (P<0.01), which were markedly enhanced by SY (P<0.05 or P<0.01). Furthermore, the enhanced effects of SY on inhibiting tumor cell growth, facilitating apoptosis and inflammatory cytokine releasing, suppressing the PD-1/PD-L1 axis, and inducing the CCL5/CXCL10 secretion in Anti-mPD-1 treated mixture of Luc-Hepa1-6 cells and CD3+CD8+ T cells were abolished by FAK overexpression (P<0.01). CONCLUSION: SY inhibited the progression of HCC by mediating immunological tolerance through inhibiting FAK.

A case series study of lacrimal canalicular laceration repair with the bi-canalicular stent.

Background: Lacrimal canalicular laceration can be caused by trauma on the ocular adnexa, such as penetrating or blunt injuries, accounting for approximately 16% of eyelid lacerations and 20% of eye traumas. Historically, canalicular anastomosis combined with bi-canalicular or mono-canalicular stent intubation has been used for canalicular laceration repair. In this study, we analyzed the epidemiological characteristics of lacrimal canalicular laceration and evaluate the clinical outcomes of repair using the bi-canalicular stent in central China. It aims to provide a reference for clinical work. Methods: This is a review of 338 patients (338 eyes) with eyelid lacrimal canaliculus laceration undergoing reparative bi-canalicular stent intubation from January 1st 2017 to December 30th 2020. The analyzed data included demographics, the place of occurrence of the trauma, the mechanism of injury, additional injury, and surgical outcomes at follow-up. The outcomes included anatomic success, functional success, and complications. Results: The average age was 39.6±20.0 years (1 to 88 years). Of all the 338 patients, 254 (75.15%) patients were men. Upper and lower canalicular lacerations were seen in 68 (20.12%) and 256 (75.74%) patients, respectively. Also, 14 patients (4.14%) presented with both upper and lower canalicular lacerations. Most injuries occurred on the streets (146, 43.20%), followed by the home in 111 (32.84%) patients. Traffic accidents were the leading cause of injury (127, 37.57%), including 72 (21.30%) cases of electric bike-associated accidents, followed by fall-related trauma in 65 (19.23%) cases. During the follow-up, there were 6 (1.78%) patients with eyelid ectropion and 9 (2.66%) patients with stent extrusion and loss due to eye rubbing and pulling the sutures out. At the end of follow-up, the anatomical success rate was 95.86% and the functional success rate was 89.64%. Conclusions: Electric bike-associated accidents occurring on the streets is the current leading cause of injury in central China. Lacrimal canalicular laceration repair with a bi-canalicular stent offers an effective surgical therapeutic strategy for traumatic canalicular lacerations. In addition, avoiding traffic accidents is also one way prevent lacrimal canalicular laceration.

Resveratrol inhibits HeLa cell proliferation by regulating mitochondrial function.

The beneficial roles of resveratrol (RES) in affecting proliferation of multiple cancer cells have attracted intensive attention. However, the underlying mechanism remains unclear. This study aims to bridge the knowledge gap by investigating RES-induced growth inhibition of HeLa cells. Our work focuses on the metergasis of mitochondria in the RES-exposed cells. Therefore, HeLa cells were treated with different concentrations of RES for 30 min and 24 h, respectively. As a result, concentration-dependent increases in cell growth inhibition, ROS (reactive oxygen species) triggering, and LC3-II (light chain 3-II) expression were detected in the HeLa cells exposed to RES for 24 h. Interestingly, a specific concentration-dependent effect was observed in the HeLa cells exposed to RES for 30 min, that is, low concentration RES (≤ 25 µmol/L) reduced ROS levels, inhibited transcription and expression levels of LC3-II, and stimulated mitochondrial respiratory capacities. In contrast, high concentration RES (50 and 100 µmol/L) induced ROS over-production and autophagy in the cells, resulting in decreased levels of mitochondrial membrane potential, mitochondrial DNA copy numbers, and mitochondrial respiratory capacities. Together, our data concluded that RES inhibited HeLa cell proliferation through perturbation of mitochondrial structure and function, and ROS-induced autophagy also played a critical role in the process.

Clinical Analysis of Adult Severe Open-Globe Injuries in Central China.

Purpose: To describe the characteristics, management, and outcomes of adult severe open-globe injured (OGI) eyes. Methods: Retrospective chart review of inpatients with initial visual acuity (VA) of light perception (LP) or no light perception (NLP) associated with OGI between 2017 and 2020 at Department of Ophthalmology, Henan Eye Institute, Henan Eye Hospital, Henan provincial People's Hospital. Results: Six hundred twenty-five eyes of 622 adult patients with initial VA of LP or NLP associated with open-globe injuries (OGIs) were included. The mean age was 47.8 ± 14.1 years with the range from 18 to 91 years. Significant male predominance was noted (81.5%). The most common type of these severe OGIs was rupture (65.8%). Traffic accidents accounted for 13.5% followed by fall/tumble (10.9%) and nail/wire (10.9%) of all the severe OGIs. Almost half of the injuries happened at workplace (47.2%). Initially, 78.7% eyes just received primary debridement and wound closure, while 8.5% eyes with no possible of anatomical reconstruction received evisceration. After initial management, 350 eyes received subsequent operation, including 239 eyes underwent vitrectomy + silicone oil/(+cataract remove). Finally, over 6 months follow-up, 137 eyes (21.9%) were eviscerated, 150 eyes (24.0%) got atrophied, while 132 eyes (21.1%) retain some VA. Fifty-three eyes (8.5%) got VA of 0.3-1.5. Conclusion: Severe OGIs are most seen in the young, middle-aged, and male working population and remain a serious public health problem, resulting in significant vision loss or Evisceration of eyes. Effective preventive measures should be taken for the individuals in these groups.

Pediatric Open Globe Injury in Central China.

PURPOSE: To describe the characteristics, managements, and outcomes of pediatric open globe injury (OGI) in central China. METHODS: Retrospective chart review of pediatric diagnosis in patients with OGI between 2017 and 2020 at Henan Eye Hospital. Four hundred and one eyes of the patients younger than 17 years were included in this study. Open globe injury was classified according to the Birmingham Eye Trauma Terminology system (BETT). Age, sex, history, cause, month of trauma, treatment received, and outcomes were recorded. Visual acuity was documented according to standard visual acuity chart (decimals). RESULTS: Four hundred and one eyes of patients were included in the study. The mean age was 6.6 ± 3.4 years with the range from 8 months to 16 years. Open globe injuries (OGIs) occurred most frequently in the 2-8 year age and significant male predominance was noted (70.8%). The incidence of pediatric OGIs was lowest in summer months while it increased in the winter months. The most common type of pediatric OGI was penetration (89%). Scissors/knife accounted for 22%, followed by pen/pencil (15.2%), and wood/bamboo sticks (14.5%) of all the pediatric OGIs. Among the injuries, the most frequently involved is the zone I (76.1%). Initially, 70.8% of the eyes received primary debridement and wound closure without any additional intervention, while only one eye has no possibility of anatomical reconstruction when it received an evisceration. After the initial management, 198 eyes received subsequent operation, including 44 eyes that underwent cataract removal + intraocular lens (IOL) implantation, and 24 eyes underwent IOL implantation. Finally, over 6 months of follow-up, 129 eyes (32.2%) got visual acuity (VA) of 0.3-1.5 and, 63 eyes (15.7%) got VA of 0.01-0.25, while 11 eyes (2.7%) were eviscerated. CONCLUSION: This study showed that pediatric OGIs in central China are most seen in 2-8-year age group with significant male predominance. Scissors/knife, pen/pencil, and wood/bamboo sticks accounted for over half of all cases. Pediatric OGIs often result in significant vision loss. In some severe cases (2.7%), evisceration was ultimately performed. We should call on the public to pay more attention to their children and build a safer environment for them.

TGF-ß2 is a Prognostic Biomarker Correlated with Immune Cell Infiltration in Colorectal Cancer: A STROBE-compliant article.

Transforming growth factor-beta (TGF-ß2) is an important cytokine regulating immune cell function. However, whether TGF-ß2 controls the invasion of colorectal cancer (CRC) by immune cells is unknown. Therefore, we evaluated the expression of TGF-ß2 using multiple databases and determined the relationship between TGF-ß2 expression and tumor immune infiltration defined by a set of genetic markers. The analysis demonstrated that the expression of TGF-ß2 is closely related to the outcome of many cancers, and this correlation was particularly strong in CRC. In addition, the increased expression of TGF-ß2 was significantly associated with the expression of various markers of specific immune cell subpopulations, and overexpression of TGF-ß2 was closely related to the prognosis of colon cancer patients. Moreover, TGF-ß2 was related to the prognosis and infiltration of the tumor by immune cells in CRC patients. The obtained results indicate that TGF-ß2 is a critical factor regulating the recruitment of immune cells and controls their infiltration into colorectal tumors. Thus, high expression of TGF-ß2 not only facilitates the prognosis in CRC patients, but also may provide a new target for the treatment of CRC.

Safety and feasibility of laparoscopic versus open liver resection with associated lymphadenectomy for intrahepatic cholangiocarcinoma.

The safety and feasibility of laparoscopic versus open liver resection (LLR vs. OLR) associated lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) are still controversial. The aim of the present study was to compare short and long-term outcomes. We reviewed data on 43 consecutive patients who underwent curative liver resection with associated lymphadenectomy for ICC. The short-term outcomes including postoperative morbidity and mortality, and the long-term outcomes including overall survival (OS) and recurrence-free survival (RFS) were compared. The median survival, 1- and 3-year OS in LLR and OLR groups were 22.5 months, 76.9% and 47.1%, and 12.1 months, 43.1% and 20.0%, respectively. The median survival, 1- and 3-year RFS in LLR and OLR groups were 10.3 months, 27.8% and 0%, and 8.1 months, 24.0% and 4.0%, respectively. The results showed that LLR obviously reduced intraoperative blood loss (median, 375 vs. 500ml, p = 0.016) and postoperative hospital stay (median, 6 vs. 9 days, p = 0.016). Moreover, there was no significant difference in short-term outcomes including postoperative morbidity (including wound infection, bile leakage, liver failure and pneumonia) and mortality within 30 days, and long-term outcomes including OS and RFS between LLR and OLR. (all p > 0.05). Multivariate analysis showed that CA19-9 level, TNM stage, and tumor differentiation were independent risk factors for OS and RFS. LLR for ICC is safety and feasibility compared with OLR. The advantage of LLR was to reduce intraoperative blood loss and postoperative hospital stay.

TFAM, a potential oxidative stress biomarker used for monitoring environment pollutants in Musca domestica.

Mitochondrial transcription factor A (TFAM) plays a key role in regulating the transcription, replication, and maintenance of mitochondrial DNA. In the present study, a Musca domestica TFAM (MdTFAM) gene was identified and characterized. MdTFAM gene encodes 253 amino acid residues, and the protein possesses two conserved motifs of HMG (High Mobility Group) box. Expression of MdTFAM was investigated based on the qRT-PCR (quantitative real-time polymerase chain reaction) in response to three model oxidative stress-inducing agents, cadmium chloride (Cd), doxorubicin hydrochloride (DOX) and ultraviolet (UV), respectively. Results showed that Cd exposure not only generated oxidative stress and mitochondrial dysfunctions in M. domestica larvae, with a significant increase in malondialdehyde and reactive oxygen species levels, but also induced a dose-dependent increase in the expression of MdTFAM. In addition, either DOX or UV exposure also significantly up-regulated the expression of MdTFAM in M. domestica larvae. These results suggest that MdTFAM play a vital role in maintaining the redox balance and its expression may serve as a useful biomarker for monitoring the oxidative stress induced by Cd, DOX or UV.

Laparoscopy versus laparotomy approach of a radical resection for gallbladder cancer: a retrospective comparative study.

BACKGROUND: Laparoscopic approach for gallbladder cancer (GBC) has long been contraindicated, but few recent studies have demonstrated the oncologic outcomes of this treatment. The purpose of this study was to compare the perioperative outcomes and long-term survival for laparoscopic surgery versus traditional open surgery of GBC. METHOD: Between January 2014 and December 2018, 63 GBC patients who received radical resection were enrolled in this study, with 32 patients in laparoscopic group and 31 cases in laparotomy group. Perioperative data and postoperative survival were retrospectively evaluated. RESULTS: Laparoscopic approach was associated with less intraoperative bleeding (267.20 ± 47.07 vs. 502.60 ± 69.70, P = 0.007), fewer postoperative days of oral diet recovery (2.34 ± 0.31 vs. 3.32 ± 0.35, P = 0.041), and hospital stay (11.03 ± 0.99 vs. 14.35 ± 1.11, P = 0.028). There were no significant differences between two groups regarding other perioperative outcomes. Patients in laparoscopic group showed better 1-year overall survival than those in laparotomy group (72.91% vs. 47.82%, P = 0.086). Subgroup analysis for GBC patients in T3 stages revealed that laparoscopic approach was associated with less intraoperative bleeding (268.00 ± 57.19 vs. 541.50 ± 101.30, P = 0.009), fewer postoperative days of hospital stay (9.87 ± 1.10 vs. 14.90 ± 1.53, P = 0.017), and improved 1-year overall survival (P = 0.023). Subgroup analysis for GBCs in TNM III and TNM IV stages showed comparable intraoperative parameters and postoperative survival between two groups. CONCLUSION: Laparoscopic surgery for GBCs may offer the comparable perioperative outcomes as conventional laparotomy procedure, and tend to be associated with less intraoperative bleeding, faster oral diet recovery, shorter hospital stay, and improved 1-year overall survival.

[Nutritional risk assessment in patients with chronic liver disease].

OBJECTIVE: To use the European Nutritional Risk Screening (NRS)-2002 survey tool to investigate nutritional risk associated to different degrees of liver disease and to assess its ability to identify the nutritional risk of hospitalized patients with chronic liver disease. METHODS: A total of 366 hospitalized patients were assessed with the NRS-2002 on the day of admission. Patients who meet the criteria for malnourishment (NRS-2002 score of more than 3 points (severely impaired nutritional status with body mass index (BMI) less than 18.5 kg/m2) were selected for further study to determine liver function. Patients were classified according to liver dysfunction-related features, including cirrhosis status, Child-Pugh classification, and underlying disease causes (e.g.alcohol, hepatitis virus infection). Chi square test was used in statistical analysis of inter-group difference. RESULTS: The incidence of patients surveyed who were at nutritional risk was 41.0%, and the incidence of malnutrition was 7.6%. The patients with liver failure showed the highest rate of nutritional risk (72.8%). Moreover, among the 97 patients with liver cirrhosis, significantly more had Child-Pugh grade B than grade A (88.6% vs.33.1%; x2=24.019, P=0.000). The cause of liver failure with the highest incidence of nutritional risk was alcohol-related liver disease (66.7%). The overall malnutrition rate among the total 156 patients classified by the NRS-2002 as being at nutritional risk was 76.2%. CONCLUSION: The NRS-2002 is a suitable screening tool for use in Chinese patients with mild early liver disease, but it must be interpreted carefully as its findings alone may promote a false positive rate. The NRS-2002 is less accurate in patients with end-stage liver disease.