Objective:To explore regulatory effects of short-chain fatty acids (SCFA) on hypoxia-induced oxidative stress and activation of pancreatic stellate cells (PSCs) .Methods:PSCs were cultured in normoxia or hypoxia conditions to establish normoxia or hypoxia group. PSCs were pre-treated with SCFA working solution (10 mmol/L sodium acetate, 0.5 mmol/L sodium propionate and 0.5 mmol/L sodium butyrate), and then cultured in hypoxia conditions to establish the hypoxia-SCFA group. PSCs pre-treated by normal saline was set as the hypoxia-control group. The relative growth viability of the cells was detected by the CCK-8 assay. Relative levels of reactive oxygen species (ROS) were detected by DCFH-DA fluorescence probe method. The mitochondrial membrane potential was detected by JC-1 fluorescence probe. Protein expression of cyclin-associated marker cyclin A and cyclin D, hypoxic marker HIF1α, activation marker α-SMA, and antioxidant marker NRF2 and HO-1 was detected by western blotting.Results:The relative viability of PSCs in hypoxia group was significantly higher than that in normoxia group at 48 h (1.23±0.05 vs 0.99±0.04), but the relative viability of hypoxia-SCFA group was significantly lower than that of the hypoxic-control group at both 36 h and 48 h (0.69±0.01 vs 0.86±0.03, 0.86±0.02 vs 1.25±0.05). The relative level of ROS was significantly higher in hypoxia group than normoxia group (1.74±0.11 vs 1.00±0.10). The relative level of ROS was significantly lower in the hypoxia-SCFA group than the hypoxia-control group (1.39±0.14 vs 1.66±0.11). The fluorescence signals of JC-1 polymer in hypoxia group were significantly higher than those in normoxia group (1.36±0.05 vs 1.00±0.11), whereas the fluorescence signals of JC-1 polymer were significantly lower in hypoxia-SCFA group than in hypoxia-control group (1.11±0.03 vs 1.32±0.06). The expression of cyclin A, cyclin D, HIF1α, α-SMA, NRF2, and HO-1 was significantly higher in hypoxia group than those in normoxia group (1.19±0.01 vs 0.63±0.02, 0.93±0.02 vs 0.83±0.03, 1.18±0.07 vs 0.41±0.02, 1.19±0.14 vs 0.66±0.04, 1.22±0.11 vs 0.61±0.04, 1.28±0.12 vs 0.68±0.02), but the expression of cyclin A, cyclin D, α-SMA, NRF2, and HO-1 in Hypoxia-SCFA group was significantly lower than those in hypoxia-control group (0.79±0.04 vs 1.15±0.03, 0.88±0.01 vs 0.95±0.03, 0.87±0.01 vs 1.18±0.05, 0.84±0.01 vs 1.22±0.04, and 0.92±0.02 vs 1.27±0.06). All these differences were statistically significant (all P values <0.05) . Conclusions:SCFA significantly improves the oxidative stress state of PSCs under hypoxic conditions, maintains the stability of mitochondrial membrane potential, and inhibites hypoxia-induced activation of PSCs.

Tumor immune microenvironment is a local external tumor environment composed of tumor immune cells and the cytokines secreted by these cells， and it plays a regulatory role in the development and progression of tumors. In the treatment of hepatocellular carcinoma， amino acid metabolism and its reprogramming of proliferating cell metabolism have attracted more and more attention， showing potential in regulating the tumor immune microenvironment. Although amino acid metabolic reprogramming is regarded as a novel approach for tumor therapy， its specific mechanism remains unclear in the regulation of tumor immunity in hepatocellular carcinoma. This article discusses the mechanism of action of amino acid metabolism in the tumor immune microenvironment of hepatocellular carcinoma and its application prospect in clinical practice， in order to provide new ideas for immunotherapy for liver cancer.

Objective:To investigate the clinical value of AB classification combined with Arima classification for predicting the invasion depth of superficial esophageal squamous cell carcinomas (SESCC).Methods:From July 2017 to December 2022, 76 cases of SESCC receiving endoscopic submucosal dissection and intra-epithelial papillary capillary loops (IPCL) AB classification as type B2 in Ningbo Medical Center Lihuili Hospital and Jiangsu Province Hospital of Chinese Medicine were included in the study. IPCL was reclassified according to Arima classification. The depth of infiltration determined by pathology was the gold standard. The sensitivity, the specificity, the positive predictive value and the negative predictive value of B2-Arima combined classification in predicting the invasion depth of SESCC were analyzed.Results:In the 76 cases of type B2 IPCL lesions, 31 cases (40.79%) were T1a-MM/T1b-SM1 SESCC. The sensitivity, the specificity, the positive predictive value, the negative predictive value and the diagnostic accuracy of type B2 IPCL to predict T1a-MM/T1b-SM1 SESCC were 70.45% (31/44), 79.64% (176/221), 40.79% (31/76), 93.12% (176/189), and 78.11% (207/265), respectively. After Arima classification, the above corresponding indicators of type B2-4ML and type B2-AVA-4M IPCL in predicting T1a-MM/T1b-SM1 SESCC were 61.36% (27/44), 88.24% (195/221), 50.94% (27/53), 91.98% (195/212), 83.77% (222/265) and 38.64% (17/44), 94.57% (209/221), 58.62% (17/29), 88.56% (209/236), 85.28% (226/265), respectively.Conclusion:B2 IPCL combined with Arima classification can improve the diagnostic accuracy of T1a-MM/T1b-SM1 ESSCC.

Objective:To investigate the application effect of preoperative prerehabilitation in elderly patients with knee arthroplasty combined with sarcopenia.Methods:A total of 164 elderly patients who were hospitalized and underwent artificial knee arthroplasty combined with sarcopenia in Department of Orthopedics of the First Affiliated Hospital of Zhengzhou University from July 2020 to December 2021 were included by the convenient sampling method. According to random number table method, they were divided into the control group and the observation group, with 82 cases in each group. The control group received routine preoperative nursing, and the observation group received preoperative pre-rehabilitation intervention on the basis of the control group. Knee range of motion, Hospital for Special Surgery Knee Score (HSS) , skeletal muscle mass index and grip strength were evaluated before intervention and 1 month after operation. Length of stay and postoperative complications were recorded and compared between the two groups.Results:Knee range of motion, HSS of two groups at 1 month after operation were higher than those before intervention, and the differences were statistically significant ( P<0.05) . One month after surgery, the knee range of motion, HSS and grip strength of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . The skeletal muscle mass index of the observation group was higher one month after surgery than before intervention, but the difference was not statistically significant ( P>0.05) . The hospitalization time of observation group was shorter than control group, and the difference was statistically significant ( P<0.05) . The incidence of complications in the observation group and control group was respectively 15.85% (13/82) and 39.02% (32/82) , and the difference was statistically significant ( P<0.05) . Conclusions:Preoperative rehabilitation can effectively improve the knee range of motion and joint function of elderly patients with sarcopenia after knee rarthroplasty, alleviate sarcopenia, shorten the length of hospital stay and reduce postoperative complications.

Objective:To explore the effect of nurse-patient cooperative rehabilitation model based on rapid recovery concept on the rehabilitation effect of patients with avascular necrosis of the femoral head undergoing artificial hip replacement.Methods:Convenience sampling was used to select 104 patients with avascular necrosis of the femoral head who were treated in the First Affiliated Hospital of Zhengzhou University from September 2019 to October 2021 and underwent artificial hip replacement. The patients were divided into control group and observation group according to the random number table method, with 52 cases in each group. The control group was given routine nursing, and the observation group was given nurse-patient cooperative rehabilitation model based on the concept of rapid recovery. The Visual Analogue Score and Harris Hip Score were compared between the two groups before and after the intervention.Results:Pain scores of the observation group were lower than those of the control group five and ten days after operation and one month after discharge, and the differences were statistically significant ( P<0.05) . After intervention, the joint pain, functional changes, deformity and joint range of motion of the observation group were better than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The nurse-patient cooperative rehabilitation model based on the concept of rapid recovery for patients with avascular necrosis of the femoral head can improve the hip joint function of patients, alleviate pain and promote rehabilitation.

Objective:To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance.Methods:A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO 2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. Results:Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO 2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (μg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (μmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO 2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ2 = 7.288, P = 0.007]. Conclusion:Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.

Objective:To investigate the relationship between the dose of preoperative neoadjuvant radiotherapy and the pathologic complete response (pCR) rate in patients with locally advanced squamous cell esophageal cancer (ESCC).Methods:Clinical data of 116 patients with ESCC who received neoadjuvant chemoradiotherapy followed by esophagectomy in our cancer center from July 2017 to December 2019 were retrospectively analyzed. The radiation doses were divided into 2 ranges based on Grays (Gy) received: 40-45 Gy and 45 Gy or more.Results:The overall pCR rate was 38. 8%(45/116). pCR was observed in 35 out of 80(44%) patients treated with 40-45 Gy and 10 of 36(28%) patients treated with 45 Gy or more. The pCR rate did not significantly differ between two groups [(40-45 Gy) vs.( ≥ 45 Gy), P=0.105)]. Conclusions:Preoperative neoadjuvant radiotherapy with a higher dose (≥ 45 Gy) fails to increase the pCR rate in patients with locally advanced ESCC. Prospective randomized trials are required to determine the optimal dose of preoperative adjuvant radiotherapy.

Objective To analyze the changes of endoplasmic reticulum stress (ERS) in the spleen of water-improving fluorosis rat,to explore the mechanism of fluoride-induced immune system damage,and to provide a scientific basis for prevention and control of endemic fluorosis.Methods Forty-eight male Wistar rats of SPF grade were randomly divided into control group and low,medium and high fluoride dose groups according to body mass (120-140 g),12 rats in each group.The sodium fluoride (NaF) content was 0,50,100 and 150 mg/L,respectively.The animals were allowed free access to water and food.After 12 weeks of fluoride exposure,6 rats in each group were selected to isolate the spleen;the remaining rats in each group were changed to drink distilled water containing no NaF,and the spleen was separated after 12 weeks of feeding.The levels of mRNA of glucoseregulated protein (GRP78),spliced X-box binding protein 1 (XBP1-s),activating transcription factor 4 (ATF4),homologous protein (CHOP) and cysteine containing aspartate specific protease 12 (Caspase-12) in spleen were determined by quantitative real-time PCR (qRT-PCR).Results Before the water-improving,the expressions of GRP78 (1.00 ± 0.09,1.69 ± 0.35,1.39 ± 0.29,1.19 ± 0.19),XBP1-s (1.00 ± 0.12,1.40 ± 0.23,1.24 ± 0.26,1.38 ± 0.11),ATF4 (1.00 ± 0.17,1.86 ± 0.56,2.33 ± 0.55,1.95 ± 0.74),CHOP (1.00 ± 0.53,2.84 ± 0.68,3.06 ± 1.29,2.50 ± 0.35) and Caspase-12(1.00 ± 0.12,1.90 ± 0.29,1.56 ± 0.35,1.76 ± 0.23) mRNA in the control group and low,medium and high fluoride dose groups were statistically significant (F =8.45,5.38,6.38,8.21,11.31,P ＜ 0.05).Except for the GRP78 in high fluoride dose group,the above indicators in fluoride groups were higher than the control group (P ＜ 0.05).After the water-improving,the expressions of GRP78 (1.00 ± 0.36,0.75 ± 0.13,0.98 ± 0.41,0.47 ± 0.19),XBP1-s (1.00 ± 0.25,0.70 ± 0.06,0.74 ± 0.17,0.65 ± 0.21),ATF4 (1.00 ± 0.51,0.66 ± 0.09,0.91 ± 0.34,0.81 ± 0.29),CHOP (1.00 ± 0.36,0.92 ± 0.12,0.84 ± 0.16,0.67 ± 0.20) and Caspase-12 (1.00 ± 0.45,0.65 ± 0.11,0.65 ± 0.25,0.51 ± 0.27) mRNA in the control group and low,medium and high fluoride dose groups were not statistically significant (P ＞ 0.05).Before and after the water-improving,the expressions of XBP1-s,ATF4,CHOP and Caspase-12 mRNA were statistically significant in fluoride groups (P ＜ 0.05),and the GRP78 only had a statistically significant difference in the low fluoride dose group (P ＜ 0.05).Conclusions Fluoride exposure causes ERS response in rat spleen,up-regulation of ERS-related gene expression,which is decreased after water-improving,and the ERS response is weakened.The water-improving may contribute to the recovery of fluoride-induced immune function damage.

OBJECTIVE: To investigate the effects of Fritillariae cirrhosae bulbus on airway inflammation and ERK/MAPK signal pathway of asthma model mice, and to explore its possible mechanism of the treatment of asthma. METHODS: The asthma model was induced by egg albumin. A total of 40 model mice were randomly divided into model group (0. 5％ carboxymethyl cellulose, intragastric administration), positive control group (0. 5 mg/kg dexamethasone, intraperitoneal injection), Fritillariae cirrhosae bulbus low-dose and high-dose groups (9. 0, 18. 0 mg/kg, intragastric administration), with 10 mice in each group. Other 10 normal mice were included in normal group (0. 5％ carboxymethyl cellulose, intragastric administration). They were given medicine once a day for consecutive 28 d. After medication, the number of total cells and differential cells (neutrophils, macrophages, lymphocytes and eosinophils) in bronchoalveolar lavage fluid (BALF) of mice were counted. The pathological morphology of bronchial smooth muscle in mice was observed under light microscope, and the inflammatory score was scored; the activities of ERK, phosphorylated ERK (p-ERK), p38 MAPK and phosphorylated p38 MAPK (p-p38 MAPK) were measured by ELISA. The protein expression of ERK, p-ERK, p38 MAPK and p-p38 MAPK in lung tissue were determined by Western blot assay. mRNA expression of ERK and p38 MAPK were determined by real time fluorescent quantitative PCR. RESULTS: Compared with normal group, the number of total cells and differential cells in BALF of mice, inflammation score, the activities of p-ERK and p-p38 MAPK in lung tissues were increased significantly of mice in model group (P<0. 01); the protein expression of p-ERK and p-p38 MAPK, mRNA expression of ERK and p38 MAPK were increased significantly in lung tissue of mice in model group (P<0. 01). Compared with model group, above indexes of treatment groups were all improved significantly (P<0. 05 or P<0. 01). CONCLUSIONS: Fritillariae Cirrhosae Bulbus can improve airway inflammation in asthma model mice, the mechanisms of which may be related to inhibiting the activation of ERK/MAPK signal pathway.

Objective To study the radiological appearance and pathological features of breast phyllodes tumors(PTs), and to enhance the knowledge of the tumor.Methods Clinical and imaging findings were reviewed retrospectively in 65 women with PTs confirmed by surgical pathology.61 patients had preoperative MRI and/or sonography, and 44 had preoperative mammography.Then these findings were compared with the pathological results.Results (1)The percentages of benign, borderline and malignant PTs were 32.3%(21/65), 43.1%(28/65) and 24.6%(16/65), respectively,and the mean maximum diameters of these lesions were (4.75±2.62) cm, (5.37±3.11) cm and (4.96±3.82) cm, respectively.There were no statistical difference in lesion''s size among these three types(F=0.247,P=0.782).(2)On the mammograms of these 44 PTs(including 16 cases of benign type, 18 cases of borderline and 10 cases of malignant type), the appearances of radiolucent halo and calcification among these three types showed statistically significant differences(both P<0.05).(3)On the sonography of these 61 PTs(including 19 cases of benign type, 26 cases of borderline and 16 cases of malignant type), the shape among these three types showed statistically significant difference(P<0.05).(4)On the MRI of these 61 PTs(including 21 cases of benign type, 24 cases of borderline and 16 cases of malignant type), internal hypointense septations on T2WI and time intensity curves showed statistically significant differences among these three types(both P<0.05).Conclusion Some radiological appearances of PTs can be used to help determine the histologic subtypes of breast PTs preoperatively.