Liver fibrosis is a common outcome of various chronic hepatic insults, characterized by excessive extracellular matrix (ECM) deposition. The precise mechanisms, however, remain largely undefined. This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3 (Pafah1b3) in liver tissues from both carbon tetrachloride (CCl₄)-treated mice and patients with cirrhosis. Deletion of Pafah1b3 significantly attenuated CCl₄-induced fibrosis, hepatic stellate cell (HSC) activation, and activation of transforming growth factor-β (TGF-β) signaling. Mechanistically, PAFAH1B3 binds to mothers against decapentaplegic homolog 7 (SMAD7), disrupting SMAD7's interaction with TGF-β receptor 1 (TβR1), which subsequently decreases TβR1 ubiquitination and degradation. Pharmacological inhibition using 3-IN-P11, a specific Pafah1b3 inhibitor, conferred protective effects against CCl₄-induced fibrosis in mice. Furthermore, Pafah1b3 deficiency reduced hepatic inflammation. Overall, these results establish a pivotal role for Pafah1b3 in modulating TGF-β signaling and driving HSC activation.

Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (Hic1), which binds to the Cx3cl1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Liver fibrosis is primarily driven by the activation of hepatic stellate cells(HSCs),a process associated with ferroptosis.Ginsenoside Rb1(GRb1),a major active component extracted from Panax ginseng,inhibits HSC activation.However,the potential role of GRb1 in mediating HSC ferroptosis remains un-clear.This study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro,using CCl4-induced liver fibrosis mouse model and primary HSCs,LX-2 cells.The findings revealed that GRb1 effectively inactivated HSCs in vitro,reducing alpha-smooth muscle actin(a-SMA)and type Ⅰ collagen(Col1A1)levels.Moreover,GRb1 significantly alleviated CCl4-induced liver fibrosis in vivo.From a mechanistic standpoint,the ferroptosis pathway appeared to be central to the antifibrotic effects of GRb1.Specifically,GRb1 promoted HSC ferroptosis both in vivo and in vitro,characterized by increased glutathione depletion,malondialdehyde production,iron overload,and accumulation of reactive oxygen species(ROS).Intriguingly,GRb1 increased Beclin 1(BECN1)levels and decreased the System Xc-key subunit SLC7A11.Further experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by GRb1.Moreover,BECN1 could directly interact with SLC7A11,initiating HSC ferroptosis.In conclusion,the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in vitro.Overall,this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation,at least partly through its modulation of BECN1 and SLC7A11.

Objective: To evaluate the consistency between prostate biopsy and postoperative pathological grade, analyze the influencing factors that may lead to upgrade or downgrade, and to establish a prediction model. Methods: The clinical data of biopsy GS3+ 3=6(GR1, 330 cases) and GS3+ 4=7(GR2, 340 cases) patients from January 2013 to December 2018 in the first affiliated hospital, College of Medicine of Zhejiang university were retrospectively analyzed. The median age was 67 years old(ranging 35 to 100 years old). The median BMI was 23.74 kg/m²(ranging 16.22-38.74 kg/m²). The Median tPSA was 10.266 ng/ml(ranging 0.017-147.575 ng/ml). The median prostate volume was 29.43 ml(5.92-187.20 ml). The median PSAD was 0.34 (ranging 0.01-4.02). The median percentage of positive puncture cores was 0.25 (ranging 0.08-1.00). There were 161 patients in clinical stage ≤T_1c, 344 patients in T_2a-T_2c and 165 patients in clinical stage ≥T₃. 670 cases all accepted the radical prostatectomy. Consistency of prostate biopsy and radical prostatectomy Gleason grade was recorded. If the postoperative Gleason grade was higher than that in biopsy, it was defined as upgrade. Otherwise, it was defined as downgrade. Multivariate logistic regression model was used to evaluate the influencing factors leading to upgrades in GR1 patients or downgrades in GR2 patients. Nomograms were drawn based on the models with AUC and Horsmer-Lemeshaw test conducted to test the discrimination and calibration of the models. Results: Among the 670 patients included, 165 cases (50.0% of GR1) upgrades and 27 cases (7.9% of GR2) downgrades. PSAD≥0.25(OR=3.015) and clinical stage≥T_2b(OR=7.185)were independent influencing factors for the upgrade in GR1 patients, while PSAD<0.15(OR=4.208) and clinical stage≤T_1c(OR=4.530) were independent influencing factors for downgrade. The nomograms were drawn with the above variables. The AUC of the model (0.781 for GR1 group, 0.741 for GR2 group) and the hosmer-remeshaw test results (P=0.993 for GR1 group, P=0.234 for GR2 group) show that the nomograms have good discrimination and calibration. Conclusions PSAD and clinical stage are independent influencing factors for the upgrade or downgrade. Nomograms may provide help for clinicians to judge the accuracy of prostate biopsy. However, the nomograms still needs to be verified in clinical practice

Objective To investigate the feasibility and plan quality of the image-guided volumetric modulated arc therapy (VMAT) based voluntary deep exhale breath-holding technique in the stereotactic ablative body radiotherapy (SABR) for liver tumors.Methods Fifteen patients with liver tumors were involved in this study.All patients were immobilized with voluntary deep exhale breath hold (vDEBH) combined with real-time position management (RPM) respiratory gating system.Treatment was planned using VMAT with 2 modified partial arc and re-planned using intensity modulated radiation therapy (IMRT) technique for comparison.Dosimetric parameters were calculated for plan quality assessment.Quality assurance studies included absolute dose and multiple planar dose verifications,total monitor units and delivery time analysis.Daily cone beam computed tomography imaging was used to verify the motions.Results There were no significant dosimetric differences between VMAT and conventional IMRT plans (P ＞0.05).Both techniques were able to minimize doses to organs at risk including normal liver,kidneys,spinal cord,and stomach.However,the average monitor units with VMAT were significantly lower 28.1％ than those with IMRT(t =3.064,P ＜0.05).The average beam-on time in VMAT plans was 31.6％ shorter than that in IMRT plans(t =2.278,P ＜ 0.05).Conclusions The utilization of VMAT in the treatment planning of SABR for liver tumors under breath control mode has better dosimetrics.In comparison to conventional IMRT plans,VMAT plans have higher efficiency and feasibility.

Objective To analyze the radiation dose to contra-lateral breasts and estimate the incidence risk of contra-lateral breast cancer for women undergone unilateral breast cancer radiotherapy.Methods The radiation doses of contra-lateral breasts for 49 patients were counted and analyzed in a hospital,and the risk of contra-lateral breast cancer in different age groups that induced by radiotherapy was estimated based on BEIR Ⅶ model combined with the Chinese lifetime table.Results The prescribed doses for the patients were all 50 Gy.The mean dose to contra-lateral breasts ranged from 0.14 Gy to 3.59 Gy,with an average of (1.21 ±0.89) Gy,and the maximum point dose varied from 0.98 Gy to 45.27 Gy,with the average of (17.42 ±13.20) Gy.Both the maximum point dose and the mean dose obviously varied among the patients,and their correlation was significant (R =0.527,P =0.000).Furthermore,no significant differences of the mean dose was found among the ages (P ＞ 0.05).The lifetime attribute risks of contra-lateral breast cancer were estimated to be 2 449,1 857,994,446,173 and 55 for per 100 thousand women corresponding to the ages of 35,40,50,60,70 and 80,respectively.Conclusions In the radiotherapy for unilateral breast cancer,the dose delivered to the contra-lateral breast is about 1 Gy order of magnitude,the risk of contra-lateral breast cancer cannot be ignored for young women.Therefore,the irradiation dose of contra-lateral breasts should be controlled as less as possible in planning the treatment.

Objective To evaluate the performance of a customized vacuum-form body immobilization method in the radiotherapy of pelvic malignancies by comparing it with conventional approaches, thus to improve immobilization accuracy in the radiotherapy of pelvic malignancies. Methods A total of 66 patients with pelvic malignancies were enrolled in this study. These patients were divided into three groups according to three immobilization approaches: radiotherapy board ( Group N ) , conventional vacuum cushion ( Group V ) , and a customized vacuum cushion specifically for pelvic immobilization ( Group New-V) . Setup deviations of these immobilizations were comparatively evaluated by translational and rotational errors during intra-fractional measurements. Results The average translational setup errors in vertical(x), longitudinal(y), lateral(z) and rotational error r were (0. 35 ± 0. 37), (0. 21 ± 0. 22), (0. 29 ± 0. 28) cm and (0. 70 ± 0. 65)° for Group New-V; (0. 44 ± 0. 43), (0. 31 ± 0. 62), (0. 45 ± 0. 60) cm and (1. 25 ± 1. 00)° for Group N; (0. 38 ± 0. 36), (0. 27 ± 0. 25), (0. 32 ± 0. 29) cm and (1. 09 ± 0. 77)° for Group V, respectively. Significant differences were observed in r direction among these three method (F=7. 859,P <0. 05). Group New-V with customized cushion showed the least standard deviations in four directions and the least setup error in r direction compared with the other two method (F=3. 166,P<0. 05). Reconstructed dose distribution based on the isocenter shift result ed from setup errors revealed that Group New-V showed the least deviations in the minimum and mean dose and of the planning target volume (PTV) before and after isocenter shift(F=8. 018, P<0. 05). Conclusions The customized vacuum cushion provided best immobilization and dosimetric advantage. It helps to optimize the immobilization accuracy and improve the clinic outcome potentially.

OBJECTIVETo compare the associated anastomotic complication of cervical esophagogastric anastomosis between stapled and hand-sewn anastomosis in minimally invasive esophagectomy(MIE).

METHODSClinical data of 203 patients with esophageal cancer receiving combined thoracoscopic and laparoscopic esophagectomy with anastomosis in the neck in our hospital from January 2010 to November 2013 were retrospectively analyzed. All the patients were divided into stapled group(104 patients) and hand-sewn group(99 patients). The incidence of anastomotic leakage and anastomotic stricture between these two groups were compared.

RESULTSThere were no significant differences between two groups in gender, age, body mass index, total protein, albumin, and neoadjuvant chemotherapy(all P>0.05). There was no significant difference between the two groups in the incidence of anastomotic leakage [6/104(5.77%) vs. 3/99(3.03%), P>0.05], while the difference in the incidence of anastomotic stricture was significant [10/104(9.62%) vs. 2/99(2.02%), P<0.05]. The time of anastomosis, dieting and hospital stay was (15.5±5.0) min, (5.0±2.8) d and (18.3±5.9) d in stapled group, which was significantly shorter than (28.0±4.5) min, (5.9±1.2) d and (21.8±4.2) d in hand-sewn group(all P<0.05).

CONCLUSIONIn the minimally invasive esophagectomy, stapled cervical esophagogastric anastomosis is simple and precise, but it is associated with increased risk of anastomotic stricture, therefore the type of anastomosis should be chosen based on the conditions of the patient.

Anastomosis, Surgical ; Anastomotic Leak ; etiology ; Constriction, Pathologic ; etiology ; Esophageal Neoplasms ; surgery ; Esophagectomy ; instrumentation ; methods ; Humans ; Laparoscopy ; Minimally Invasive Surgical Procedures ; instrumentation ; methods ; Retrospective Studies ; Sutures ; Treatment Outcome

Objective To compare the associated anastomotic complication of cervical esophagogastric anastomosis between stapled and hand-sewn anastomosis in minimally invasive esophagectomy (MIE). Methods Clinical data of 203 patients with esophageal cancer receiving combined thoracoscopic and laparoscopic esophagectomy with anastomosis in the neck in our hospital from January 2010 to November 2013 were retrospectively analyzed. All the patients were divided into stapled group (104 patients) and hand-sewn group (99 patients). The incidence of anastomotic leakage and anastomotic stricture between these two groups were compared. Results There were no significant differences between two groups in gender, age, body mass index, total protein, albumin, and neoadjuvant chemotherapy (all P>0.05). There was no significant difference between the two groups in the incidence of anastomotic leakage[6/104(5.77%) vs. 3/99(3.03%), P>0.05], while the difference in the incidence of anastomotic stricture was significant [10/104(9.62%) vs. 2/99(2.02%), P<0.05]. The time of anastomosis, dieting and hospital stay was (15.5±5.0) min, (5.0±2.8) d and (18.3±5.9) d in stapled group, which was significantly shorter than (28.0±4.5) min, (5.9±1.2) d and (21.8±4.2) d in hand-sewn group (all P<0.05). Conclusion In the minimally invasive esophagectomy, stapled cervical esophagogastric anastomosis is simple and precise , but it is associated with increased risk of anastomotic stricture, therefore the type of anastomosis should be chosen based on the conditions of the patient.