"State-target-cause-result"is a new clinical theory combining macroscopic and microscopic syndrome differentiation based on the holistic view of traditional Chinese medicine combined with Western medical research.The"inflammation-cancer transformation"of chronic pancreatitis is a complex pathological process that is associated with the interaction between the pancreas and various pathological factors and multiple objects,involving the imbalance of multiple homeostasis.The microscopic process of"inflammation-cancer transformation"in chronic pancreatitis is the"target,"whereas various factors that could induce its occurrence under chronic inflammatory conditions are the"state."The"inflammation-cancer transformation"of chronic pancreatitis is summarized as yin and yang imbalance,qi movement disorder,endogenous dampness,heat,blood stasis,and turbid phlegm stagnation,unresolved congestion resulting in deficiency caused by stagnation,intermingled deficiency and excess,and internal cancer toxin generation.This paper elucidates the pathogenesis and intervention strategies of the"inflammation-cancer transformation"of chronic pancreatitis from a macro perspective of"state,"focusing on reducing the impact of"state"imbalance on the"target"to establish a balanced pancreas-immune-microbiota state.The aim is to broaden the theory for exploring the mechanism and drug development related to chronic pancreatitis"inflammation-cancer transformation"in both traditional Chinese and Western medicine.

Objective:To establish an isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method for the determination of L-tryptophan and its metabolites in serum.Methods:The methodology was established and evaluated using serum samples collected from 166 healthy subjects undergoing physical examinations at West China Hospital from November 2022 to January 2023 were collected. Isotope-labeled markers of L-tryptophan (Trp), L-kynurenine (Kyn), and kynurenic acid (KA) were used as internal standards. After protein precipitation treatment of serum samples, LC-MS/MS was used to determine Trp, Kyn, and KA simultaneously. The selectivity, specificity, linearity, detection limit (LOD), quantification limit (LOQ), carry-over, precision, recovery rate, matrix effect, and dilution integrity of the method were evaluated.Results:The linearity of Trp, Kyn, and KA was demonstrated to be 0.999. The LODs were 0.10 μmol/L, 0.01 μmol/L and 1.00 nmol/L, respectively. The LOQs were 0.20 μmol/L, 0.04 μmol/L and 2.00 nmol/L, respectively. The intra-batch precision and inter-batch precision were below<10%. The average recovery rate and the relative matrix effect were all about 100%. The samples over the upper limit of quantitation can be diluted up to 16 times. The Trp concentration, Kyn concentration, KA concentration, Kyn/Trp ratio, and KA/Kyn ratio in serum of healthy subjects were 59.55±10.92 μmol/L, 1.85±0.43 μmol/L, 39.89±17.93 nmol/L, (31.64±8.19)×10 -3 and 21.51±6.72, respectively. Conclusion:An ID-LC-MS/MS method was successfully established for the quantitative determination of Trp, Kyn, and KA in serum. The method proved to be simple, rapid, sensitive, accurate, and reliable, providing robust support for clinical research related to these analytes.

Objective     To investigate the risk factors for postoperative complications Clavien-Dindo classification≥grade Ⅱ after lung cancer surgery. Methods     The patients who underwent lung cancer surgery in a multicenter observational study from November 2017 to January 2020 were included. The Clavien-Dindo classification of postoperative complications was analyzed. Logistic regression was used to identify the risk factors for complications≥ gradeⅡ. Results     A total of 388 patients were enrolled, including 203 males and 185 females with a mean age of 56.14±10.36 years. The incidence of postoperative complications was 25.52% (99/388) after lung cancer surgery and the incidence of complications≥gradeⅡ was 20.10% (78/388). The five most common postoperative complications were pneumonia (6.96%), prolonged pulmonary air leak (>7 days, 5.67%), incision dehiscence (4.64%), arrhythmia (3.87%), and postoperative pleural effusion (3.35%). Multivariate analysis showed that open surgery [reference: uniportal thoracoscopic surgery, OR=2.18, 95%CI (1.01, 4.70), P=0.047], extended resection [reference: sublobar resection, OR=2.86, 95%CI (1.11, 7.19), P=0.030; reference: lobectomy, OR=2.20, 95%CI (1.10, 4.40), P=0.026] and operative time≥3 h [OR=2.07, 95%CI (1.12, 3.85), P=0.021] were independent risk factors for postoperative complications≥gradeⅡ after lung cancer surgery. Conclusion     Surgical approach, extent of resection and operative time are independent influencing factors for postoperative complications≥gradeⅡ after lung cancer surgery.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

Objective:To evaluate the clinical value of 5.0 T ultra-high filed MRI system in assessing intracranial arteries segments and vessel branchers.Methods:This study was a prospective study. Totally 40 consecutive healthy volunteers were recruited from Zhongshan Hospital, Fudan University from September 1, 2021 to November 30, and all participants who underwent either 3.0 T or 5.0 T time-of-flight MR angiography (TOF-MRA) in random order were divided into 3.0 T MR group and 5.0 T MR group with 20 volunteers for each group. Image quality was assessed by Likert 5 scoring systems and signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR),and score in visualization of intracranial arteries [middle cerebral artery (MCA) and its segments, anterior cerebral artery (ACA) and its segments, posterior cerebral artery (PCA) and its segments, lenticulostriate arteries (LA) and pontine artery (PA)] were assessed from 0 to 3 (≥2: good depiction of vessel segment). Quantitative indicators were compared between 2 groups using independent t test or Mann-Whitney U test. Results:Among the 40 subjects, there were 29 males and 11 females, aged 20-69 (50±12) years. SNR and CNR were both significantly higher in 5.0 T MR group than those in 3.0 T MR group (SNR: 187±9 vs 91±4, t=31.59, P<0.001; CNR: 156±7 vs 70±4, t=31.45, P<0.001), but there was no significant difference in subjective scores of image quality between the 5.0 T MR and 3.0 T MR groups [5.0 (4.0, 5.0), 5.0 (5.0, 5.0) points, respectively, Z=-1.23, P=0.218]. In the evaluation of cerebral arteries, the visualizations of the proximal and middle segments of MCA, ACA and PCA was better than those in the 3.0 T MR group, and there was no significant difference in the scores ( P>0.05), while the visualizations of proximal arteries in the 5.0 T MR group were significantly better than those in the 3.0 T MR group ( P<0.05). Furthermore, small vessel branches such as LA and PA in 5.0 T MR group were visualized better than those in 3.0 T MR group ( P<0.001). Conclusion:TOF-MRA by ultra-high filed 5.0-T provides an optimal choice in visualization of distal large arteries and small vessel branches, which could be useful for the diagnosis on cerebral vascular disease.

Objective To explore the effect of primary exchange reamed nailing (ERN) and augmentation compression plating (ACP) combined with autogenous bone grafting (ABG) on health-related quality of life in patients with dystrophic or atrophic nonunion of femoral shaft after intramedullary nailing. Methods The study used a prospective study method. Sixty- two patients with femoral shaft nonunion after intramedullary nailing from August 2010 to October 2016 were selected, and the patients were divided into ERN group (group A, 32 cases) and ACP group (group B, 30 cases) by random digits table method. In group A, isthmus nonunion was in 18 cases (56.2％), and non-isthmus nonunion in 14 cases (43.8％); in group B, isthmus nonunion was in 16 cases (53.3％), and non-isthmus nonunion in 14 cases (46.7％ ). The health- related quality of life was compared between 2 groups, including physical component summary (PCS) and mental component summary (MCS) in the- 12- item short form health survey (SF- 12), brief pain inventory- severity (BPI- S) and brief pain inventory- interference (BPI- I). Results Fifty-four patients were followed-up for more than 1 year, and the mean follow-up time was 18.3 (13 to 37) months. All patients successfully achieved bone union, and the mean time was 5.8 (4 to 8) months. Significant improvements in terms of SF-12 PCS and SF-12 MCS score were noted after operation for patients with isthmus nonunion in both groups (t=3.148, 2.156, 2.456 and 2.559; P < 0.05), but there were no significant differences before and after operation in group A with non-isthmus nonunion (P >0.05). At the last follow-up, SF-12 PCS and SF-12 MCS in group B were significantly improved compared with those in group A: (45.2 ± 5.8) scores vs. (33.6 ± 4.7) scores and (48.8 ± 6.5) scores vs. (39.4 ± 5.6) scores, and there were statistical difference (P<0.05); SF-12 BPI-S and BPI-I showed obvious relief: (4.6 ± 2.1) scores vs. (6.2 ± 2.5) scores and (5.2 ± 1.9) scores vs. (6.8 ± 2.7) scores, and there were statistical differences (P<0.05); however there were no statistical difference in SF-12 PCS, SF-12 MCS, BPI-S and BPI- I between 2 groups (P>0.05). Conclusions Compared with ERN combined with ABG, ACP combined with ABG can significantly improve the quality of life in patients with dystrophic or atrophic nonunion of femoral shaft after intramedullary nailing. It has greater advantage on the improvement of health-related quality of life, especially for patients with non-isthmus nonunion.

Objective To analyze the related risk factors of re-nonunion after primary revision for femoral shaft nonunion subsequent to failed intramedullary nailing. Methods A retrospective study was performed in 61 patients with femoral shaft nonunion subsequent to failed intramedullary nailing from June 2008 to June.All patients were divided into re-nonunion group(22 cases)and non-re-nonunion group (39 cases) according to diagnostic criteria of bone re-nonunion. Univariate analysis was used to analyze 14 factors that may lead to the occurrence of re-nonunion after revision for femoral shaft nonunion subsequent to failed intramedullary nailing including age, gender, body mass index (BMI), smoking, alcohol abuse, injury reason, fracture types, intramedullary nail types, locking screws technology for intramedullary nail, bone nonunion sites, bone nonunion time, pathological types of bone nonunion, primary revision methods and autologous bone graft or not, and multi-factor logistic regression analysis was performed on the factors showing a significant difference. Results Univariate analysis showed significant difference in smoking (χ2= 6.564, P = 0.036), BMI (χ2= 6.783, P = 0.021), bone nonunion sites(χ2=7.316,P=0.011),primary revision methods(χ2=8.069,P=0.003)and autologous bone graft or not(χ 2=6.668,P=0.027).Logistic regression analysis showed that primary revision methods(OR=1.027,95% CI 0.028-0.463,P<0.05)and autologous bone graft or not(OR=1.024,95% CI 0.006-0.363, P < 0.05) were independent risk factors for re-nonunion after revision of femoral shaft nonunion subsequent to failed intramedullary nailing. Conclusions Primary revision methods and autologous bone graft or not are independent risk factors for re-nonunion after revision of femoral shaft nonunion subsequent to failed intramedullary nailing.By strictly controlling the surgical indications and combining with autogenous bone grafting,it is possible to reduce the occurrence of nonunion after primary revision of the femoral shaft nonunion subsequent to failed intramedullary nailing.

Objective To analyze the related risk factors for Lisfranc injury resulting from low energy violence.Methods A retrospective study was performed for 61 cases (35 males,26 females) with low-energy foot injury hospitalized from June 2008 to June 2014.Mean age was 36.7 years (range,16-57 years).Fall injuries were noted in 24 cases,sports injuries in 21 cases,and twist injuries in 16 cases.The cases were divided into Lisfranc injury group(n =23) and non-Lisfranc injury group (n =38) according to the different diagnosis.Univariate analysis and multi-factor logistic regression analysis were used to identify the factors that may lead to the occurrence of Lisfranc injury including age,gender,body mass index,operation history,smoking,alcohol abuse,injury reason,medial depth of the mortise/ second metatarsal length (b/a),lateral depth of the mortise/ second metatarsal length (c/a),first metatarsal-to-talus angle,first intermetatarsal angle,second metatarsal length/foot length(a/g),calcaneal inclination angle and cuboid-navicular overlap/cuboid vertical height (e/e + f).Results Univariate analysis showed between-group differences were significant in age (x2 =7.385,P ＜0.05),injury reason (x2 =8.663,P ＜ 0.05),calcaneal inclination angle (t =3.958,P ＜ 0.05),b/a (t =5.051,P ＜ 0.05) and a/g(t =4.618,P ＜ 0.05).Logistic regression analysis identified b/a(OR =1.036,95 ％ CI 0.018-0.450,P ＜ 0.01) and a/g(OR =1.013,95％ CI 0.005-0.374,P ＜ 0.01) as independent risk factors for low-energy Lisfranc injury.Conclusion Low-energy Lisfranc injury is independently associated with b/a and a/g,and may relate to the decreased medial depth of the mortise and increased foot length.

Objective To investigate the role of a small RNA interference against VEGF in radiation sensitivity in melanoma .Methods A375 human melanoma cell lines were transplanted into nude mice ,which with malignant melanoma were randomly divided into control group , VEGF negative plasmid group and VEGF positive plasmid group, followed by 4Gy irradiation twice a week for 2 weeks.The volume of tumor was calculated twice a week, the area of tumor necrosis was assayed by HE,the expression of VEGF in tumor was determined by Western-blot and Immunohistochemical. ResuIts The expression of VEGF in VEGF positive plasmid group decreased significantly (P<0.05), VEGF positive group had more tissue necrosis, tumor growth was significantly inhibited (P<0.05).ConcIusion siRNA-VEGF in tumor injection liposome encapsulated in malignant melanoma has a role in the radiation sensitization, which provides an experimental basis for the clinical development of targeted therapy combined with radiotherapy for the treatment of VEGF gene.

Objective To study the inhibitory mechanism of soliquiritigenin on tyrosinase.Methods The inhibition effect and inhibitory kinetics of tyrosinase induced by oliquiritigenin were investigated.The effect of isoliquiritigenin on A375 melanoma cell were preliminarily indicated.Results The inhibitory effect of isoliquiritigenin on monophenolase and diphenolase of tyrosinase was good, IC50 was (11.22 ±0.92) μM and (48.53 ±4.75) μM, isoliquiritigenin was a competitive inhibitor, the value of inhibition constant ( Ki ) was ( 12.14 ±0.54 ) μM.Isoliquiritigenin could inhibit the prolifevation of A375 cell significantly, and the tyrosinase activity and melanin synthesis decreased.Conclusion Isoliquiritigenin as a tyrosinase inhibitor, plays an important role in the regulation of melanin, which provides the theoretical basis for the clinical anti skin cancer.