[Objective] To investigate professor SHAN Zhaowei's experience of diagnosing and treating bile reflux gastritis(BRG). [Method] The experience of Professor SHAN Zhaowei on recognition of etiology and pathogenesis, treatment principle, characteristics of prescription selection and administration of BRG is summarized and studied. Besides his academic ideas and clinical medication experience are shown with typical cases. [Result] In his view, emotional disorder is the most common etiology, and liver-stomach disharmony is the basic pathogenesis. He puts forward that we should pay attention to dispersing the stagnated liver Qi, regulating the stomach to lower the adverse flow of Qi when we treat it, and emphasizes the combination of disease differentiation and syndrome differentiation. Meanwhile, herbs of protecting gastric mucosa are compatibly used to improve the curative effect. And the case in this article has obtained good treatment results. [Conclusion] Pro. SHAN Zhaowei thinks that emotional regulation to patency for patients is very important. The dispersing the stagnated liver Qi, regulating the stomach and protecting gastric mucosa treatment proposed by SHAN Zhaowei is smart, simple and effective, which embodies the characteristic of his healing and MengHe Medicine.

Objective To observe the effect of JLP on transdifferentiation of human renal proximal tubular epithelial cells (HK-2),and to investigate the role of p38 MAPK signaling pathway in this process.Methods The knock-down plasmids of JLP were constructed.HK-2 cells were randomly divided into four groups:negative control cells (Ctrl-shRNA group),knock-down jlp cells (jlpshRNA group),negative control cells with FGF-2 treatment (FGF-2 group) and knock-down jlp cells with FGF-2 treatment(jlp-shRNA +FGF-2 group).The expressions of JLP,E-cadherin,TGF-β1,α-SMA,p-p38 MAPK protein were detected by Western blotting.After the induction of FGF-2 for 24 hours,the expressions of α-SMA,COL-Ⅰ,FN were detected by immunocytochemistry.Results Compared with Ctrl-shRNA group,the expression of JLP protein was significantly down-regulated in FGF-2 group.Compared with FGF-2 group,the expressions of TGF-β1,α-SMA,p-p38 MAPK protein were significantly up-regulated,while E-cadherin protein was significantly down-regulated (P ＜ 0.05).Compared with FGF-2 group,the expressions of α-SMA,COL-Ⅰ,FN immunostaining increased markedly in jlp-shRNA+FGF-2 group.Conclusion Scaffolding protein JLP is critical in preventing EMT in the course of fibrosis through the inhibition of p-p38 activation in HK-2 cells.

Objective To observe the effect of JLP deficiency on the progression of renal interstitial fibrosis in mice model of unilateral ureteral obstruction (UUO),and to investigate the role and underlying mechanism of JLP in the development of renal fibrosis in obstructive nephropathy.Methods jlp Wild type (jlp+/+) and jlp deficient (jlp-/-) mice were divided into four groups:jlp+/+-and jlp-/--sham-operated groups(jlp-/--sham group and jlp+/+-sham group),jlp+/+-and jlp-/--unilateral ureteral obstruction (UUO)-operated groups (jlp/--UUO group and jlp+/+-UUO group).Mice were sacrificed at 7 days and 14 days after the operation respectively to evaluate the fibrosis by Masson staining.The expression of JLP in jlp +/+ renal tissue was assayed by immunohistochemistry staining,immunofluorescence and Western blotting.Immunohistochemical staining was used to detect the expression of α-smooth muscle actin (α-SMA),collagen Ⅰ (COL-Ⅰ),collagen Ⅲ (COL-Ⅲ) and transforming growth factor-β1 (TGF-β1) in sham and UUO groups.Besides,the α-SMA,COL-Ⅰ,COL-Ⅲ,TGF-β1,p-Smad2 and p-Smad3 protein levels were also analyzed by Western blotting in four groups.Results The expression of JLP was mainly demonstrated in the renal tubules of mice.A large amount of collagen deposition was observed in the renal interstitial area in jlp-/--UUO group compared to jlp+/+-UUO group.Similarly,the expression of α-SMA,COL-Ⅰ,COL-Ⅲ and TGF-β1 was significantly increased in the kidney cortices in jlp-/--UUO-operated groups.Meanwhile,Western blotting showed that the expression of α-SMA,COL-Ⅰ,COL-Ⅲ,and TGF-β1 protein was obviously higher in jlp-/--UUO group.Moreover,the expression of p-Smad2 and p-Smad3 protein was markedly higher in jlp-/--UUO group.Conclusion Scaffolding protein JLP is critical in preventing renal fibrosis through the inhibition of TGF-β1 expression and myo-fibroblast production.

OBJECTIVE:To observe the clinical efficacy and safety of Xiaozhen zhiyang spray in the treatment of EGFRI-asso-ciated rash. METHODS:A total of 60 malignant tumor patients suffering from rash induced by EGFRI were divided into trial group (40 cases)and control group(20 cases)according to the patient's willingness. Control group didn't received any therapy for rash. Trial group received Xiaozhen zhiyang spray for several times a day according to the degree of rash as 1-2 times/d for first degree, 2-3 times/d for second degree,3-5 times/d for third degree,and the treatment course lasted for 2 weeks. Rash degree and improve-ment,itching degree and improvement,daily life quality index(DLQI)score before and after treatment as well as the occurrence of ADR were compared between 2 groups. RESULTS:before treatment,there was no statistical significance in rash and itching de-gree,or DLQI score between 2 groups(P>0.05). After treatment,rash and itching degree of trial group were improved significant-ly compared to before treatment and control group,with statistical significance(P<0.05). The total response rates of rash and itch-ing therapy in trial group were significantly higher than control group(67.50% vs. 20.00%,70.00% vs. 15.00%),with statistical significance(P<0.05). DLQI score of trial group was significantly lower than before treatment and control group,with statistical significance(P<0.05). There was no statistical significance in DLQI score of control group before and after treatment(P>0.05). No obvious ADR was found in trial group. CONCLUSIONS:Xiaozhen zhiyang spray can effectively relieve EGFRI-associated rash and itching as well as improve the quality of life for patients.

Objective:To investigate the synergistic effects and molecular mechanisms of dihydroartemisinin(DHA) and sorafenib(SOR) in inducing ferroptosis in anaplastic thyroid cancer(ATC) cells.Methods:CCK-8 and flow cytometry assays were performed to detect the effects of DHA and SOR on the proliferation and ferroptosis of ATC cells(CAL-62). Real-time fluorescence quantitative PCR and Western blotting assays were performed to detect the expressions of ferroptosis-related genes glutathione peroxidase 4(GPX4), solute carrier family 7 member 11 gene(SCL7A11), lipoxygenase-15(LOX-15), and p53. The levels of iron death intermediate metabolites including lactate dehydrogenase(LDH), glutathione(GSH), malondialdehyde(MDA), ferrous ion(Fe 2+ ), nitric oxide(NO), and reactive oxygen species(ROS)were measured by corresponding assay kits. The corresponding inhibition of DHA and SOR on ATC in vivo was analyzed in a tumor model in nude mice. Results:Compared with the control group, DHA, SOR, and DHA+ SOR treatment significantly inhibited cell proliferation and apoptosis in a dose-dependent manner( P<0.001), with increased LDH, Fe 2+, MDA, and ROS contents and reduced GSH activity( P<0.001), which were promoted by ferrous sulfate(FeSO 4)and reversed by ferroptosis inhibitor-1. Compared with the control group and the drug monotherapy group, 15-LOX-2 and p53 expressions were upregulated in DHA+ SOR group while GPX4 and SCL7A11 expressions were decreased( P<0.001), without significant difference in 15-LOX-1 protein content. In addition, NO level was significantly increased in DHA+ SOR group( P<0.001). DHA and SOR inhibited tumor growth of ATC in vivo. Conclusion:DHA and SOR synergistically induced ferroptosis via upregulating the expression of 15-LOX-2 gene and inhibiting NO synthesis in ATC cells.

Objective:To investigate the predictive value of early thyroid function changes on the efficacy of patients with Graves′ disease (GD) after 131I therapy. Methods:Data of patients with GD (59 males, 214 females; age (37.4±11.4) years) who underwent single therapy of 131I in Tianjin Medical University General Hospital from November 2017 to January 2019 were retrospectively analyzed. Symptoms, signs and laboratory tests (serum free triiodothyronine (FT 3) and serum free thyroxine (FT 4)) of patients were observed to assess the efficacy of 131I treatment. Efficacy was divided into complete remission (CR), partial remission (PR), non-remission (NR) or relapse. The changes of thyroid function (ΔFT 3=FT 3 before treatment-FT 3 after treatment)/FT 3 before treatment×100%; ΔFT 4=FT 4 before treatment-FT 4 after treatment)/FT 4 before treatment×100%) 1 month after 131I therapy in each efficacy group and differences among them were compared by using independent-sample t test, χ2 test, one-way analysis of variance and the least significant difference t test. ROC curves were drawn to analyze the predictive values of early thyroid function changes on the efficacy of 131I treatment for GD. Logistic regression analyses were performed to identify the influencing factors for the efficacy of 131I therapy. Results:CR rate and total effective rate of 273 GD patients after single therapy of 131I were 67.03%(183/273) and 92.67%(253/273), respectively. After 1 month, CR rate of euthyroidism group ( n=95) was significantly higher than that of hyperthyroidism group ( n=178; 81.05%(77/95) vs 59.55%(106/178); χ2=4.60, P=0.032). ΔFT 3 and ΔFT 4 at the first month were statistically significant and decreased sequentially in the CR group ( n=183), PR group ( n=70), NR or relapse groups ( n=20; F values: 15.40, 12.54, both P<0.001). ROC curve analysis showed that patients with ΔFT 3≥73.64% and (or) ΔFT 4≥59.03% had a higher probability of achieving CR, with sensitivities of 84.3% and 86.7%, and specificities of 62.6% and 62.6%, respectively. Logistic regression analysis showed that 24 h radioactive iodine uptake (odds ratio ( OR)=1.095, 95% CI: 1.031-1.139), dose of 131I given per gram of thyroid tissue ( OR=1.562, 95% CI: 1.321-1.694), ΔFT 3 ( OR=1.354, 95% CI: 1.295-1.482), ΔFT 4 ( OR=1.498, 95% CI: 1.384-1.608) were factors affecting the outcome of patients with GD treated with 131I treatment (all P<0.05). Conclusion:Effects of 131I treatment can be predicted based on the change of the thyroid function at the first month after 131I treatment in patients with GD.

Objective:To explore the association between body mass index (BMI) and the incidence of thyroid nodules, the clinical characteristics and efficacy evaluation of differentiated thyroid cancer (DTC), respectively.Methods:Clinical data of 1 375 healthy people (1 031 males, 344 females, age: (43.5±10.6) years) who underwent routine physical examination (PE) and 1 450 patients (490 males, 960 females, age: (44.3±12.4) years) with medium-high risk DTC in Tianjin Medical University General Hospital from April 2016 to July 2020 were analyzed retrospectively. PE and DTC patients were classified into underweight group (BMI<18.5 kg/m 2), normal weight group (18.5≤BMI<24.0 kg/m 2), overweight group (24.0≤BMI<28.0 kg/m 2) and obesity group (BMI≥28.0 kg/m 2) respectively. χ2 test was employed to analyze the relation between BMI and thyroid nodules (with/without), BMI and clinical characteristics and efficacy evaluation of DTC, respectively. Logistic regression analysis was used to analyze the independent risk factors for the occurrence of thyroid nodules and the aggressiveness of DTC. Results:Among PE, there were 779 cases with nodules, and 596 cases without nodules. Comparing with those without nodules, more overweight and obese were found in PE cases with nodules (42.1%(328/779) vs 37.2%(222/596), 24.5%(191/779) vs 20.5%(122/596); χ2=13.42, P=0.004). Higher risk of developing thyroid nodules was related with older age and lower thyroid stimulating hormone (TSH) level (odds ratio ( OR): 1.044, 0.919, 95% CI: 1.029-1.060, 0.845-0.999; P<0.001, P=0.046). People with high-risk nodules were more likely to be obese than those with intermediate and lower risk nodules (5/15 vs 24.3% (186/764); χ2=21.11, P<0.001). Among 1 450 DTC patients, comparing with patients with normal weight, patients in the overweight and obesity groups were more likely to have central regional lymph node metastasis ( OR: 1.418, 1.427, 95% CI: 1.075-1.870, 1.044-1.952; P values: 0.013, 0.026), and patients in obese group were with greater risk of lesions being bilateral ( OR=0.696, 95% CI: 0.519-0.934; P=0.016). BMI was not related with the efficacy evaluation of DTC ( χ2=9.13, P=0.425). Conclusions:The incidence of thyroid nodules in people with high BMI is higher. DTC patients with high BMI may have more aggressive incidence. But BMI has no correlation with the efficacy evaluation of DTC patients after treatment.

Objective:To evaluate the technical approach and application value of DynaCT biliary reconstruction with CT images fusion (DynaCT-CT fusion) for the treatment of complex hepatolithiasis.Methods:The data of 18 patients with complex hepatolithiasis admitted to the First Affiliated Hospital of Guangzhou Medical University from May 2022 to October 2022 were retrospectively analyzed, including 7 males and 11 females, aged (50.6±15.0) years. Preoperative DynaCT biliary reconstruction with CT images fusion was performed to guide the percutaneous transhepatic one-step biliary fistulation (PTOBF). The technical data, including the bile duct with stones identified by preoperative imaging, the actual bile duct with stones confirmed intraoperatively, the satisfied stone removal time for each targeted bile duct, the actual stone removal time for each targeted bile duct, the intraoperative identification of CT-negative stones, the postoperative complications and reoperation were analyzed.Results:In 18 patients, a total of 95 target bile ducts with stones were identified by preoperative DynaCT-CT fusion technology, involving the first, secondary and tertiary bile ducts. Preoperative CT identified 29 lesions of stones involving the first and secondary bile ducts. CT negative stones were confirmed in 5 patients by DynaCT-CT fusion. Bile duct stricture occurred in 12 patients. All procedures were completed without postoperative bile leakage or hemorrhage. A total of 82 lesions of stones were successfully removed with a removal time of (25.9±12.8) min. The satisfied stone removal time for each targeted bile duct was (10.1±7.6) min, and the actual stone removal time was (10.5±7.4) min. Immediate stone clearance was achieved in 13 patients. Biliary tract infection occurred in 2 patients, and 5 patients underwent reoperation for residual or recurrent stones.Conclusion:The DynaCT-CT fusion technology guided PTOBF is feasible and safe in patients with complex hepatolithiasis. It could effectively detect more stones, shorten the stone clearance time. DynaCT-CT fusion technology provides a new strategy for the treatment of hepatolithiasis.

Objective:To explore the role and molecular mechanism of Shikonin(SKN) in inhibiting the growth of anaplastic thyroid carcinoma(ATC) cells.Methods:The effect of SKN on ferroptosis in ATC cell lines CAL-62 was detected by flow cytometry; the expression levels of NF-κB, ferroptosis-related genes glutathione peroxidase 4(GPX4) and selenoprotein thioredoxin reductase 1(TXNRD1), glucose metabolism-related genes pyruvate kinase isoform 2(PKM2) and glucose transporter protein 1(GLUT1) were detected by Western blotting; real-time fluorescence quantitative(qPCR) to detect changes in the expression levels of GPX4, PKM2 and GLUT1; reactive oxygen species(ROS) fluorescent probe to detect changes in intracellular ROS positivity; glucose and lactic acid assay kit to detect the levels of glucose, the raw material of glucose metabolism(GLU), and lactate(LD), the product of glucose metabolism; and establishment of a subcutaneous tumour model in BALB/c nude mice to analyse the inhibitory effect of SKN on ATC in vivo.Results:Compared to the control group, after SKN treatment, the protein expression levels of NF-κB, GPX4, TXNRD1, GLUT1, and PKM2 in CAL-62 cells decreased( P=0.004, P=0.012, P=0.043, P=0.001, P=0.018); the mRNA expression of GPX4, GLUT1, and PKM2 also decreased( P<0.001, P=0.029, P<0.001). Additionally, ROS production increased( P=0.041). After treatment with the ferroptosis inhibitor Liproxstatin-1(L-1), the proportion of cell death was reversed to a certain extent, and there was no statistically significant difference in cell death proportion after L-1 treatment. Intracellular ferroptosis occurred( P<0.001), with reduced levels of glutamate(GLU) uptake and lipid peroxidation(LD) generation( P<0.001). SKN inhibited ATC tumor growth in vivo( P=0.016). Conclusion:SKN promotes intracellular ferroptosis in ATC cells, inhibits glycolysis and glucose uptake, and suppresses ATC cell growth.

Objective:To investigate the mechanism of benzyl isothiocyanate(BITC) in the treatment of anaplastic thyroid cancer(ATC).Methods:Using network pharmacological analysis, key targets of BITC and ATC were screened, followed by GO and KEGG enrichment analysis. In order to validate the findings, AutoDock software was used to dock BITC and ATC key targets. BITC was applied to two ATC cell lines(8505C and CAL-62). Flow cytometry was used to analyze cell apoptosis. Autophagy inhibitors hydroxychloroquine sulfate(HCQ) and 3-methyladenine(3MA) were used in combination with BITC. Real-time quantitative PCR was conducted to detect the gene level of LC3B, while Western blotting was utilized to examine the expression of NF-κB, LC3B Ⅱ, Beclin-1, and Bcl-2. In animal experiments, a mouse tumor model was constructed using CAL-62 cells, treated with intraperitoneal injections of BITC(100 mg/kg) and normal saline respectively, administered every other day for a total of 21 days. Immunoblotting of tumor tissue was performed to detect the expression of LC3B Ⅱ, Bcl-2, Beclin-1, and NF-κB.Results:A total of 10 key targets with binding energies≤-4.0 kcal/mol were identified. KEGG analysis showed that these genes are mainly involved in NF-κB signaling pathway and apoptosis. BITC inhibited ATC cells with IC50 values of 27.56 μmol/L for 8505C and 28.30 μmol/L for CAL-62. The expression levels of NF-κB, Beclin-1, and Bcl-2 decreased, while LC3B Ⅱ and LC3B gene expression increased. Combining 3MA with BITC enhanced cell inhibition LC3B Ⅱ expression. HCQ increased LC3B Ⅱ expression without enhancing cell and viability inhibition. In the mouse tumor model, compared to the control group, the treatment group had higher LC3B Ⅱ and lower Bcl-2, Beclin-1, and NF-κB levels.Conclusion:BITC could inhibit the growth of ATC cells in vitro and in vivo, disrupt the autophagy degradation, and inhibit the NF-κB pathway.