Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

OBJECTIVES: To establish a rapid and nondestructive identification method for human body fluid stains and non-biological stains using three-dimensional fluorescence spectroscopy. METHODS: The collected three-dimensional fluorescence spectrum data of human saliva, 3% blood, coffee and Fanta^® stains were processed with dimensionality reduction. After wavelet transform, spectral denoising and feature extraction, the classification formula was established. The Fisher discriminant was used for spectrum matching and recognition to establish the analysis method to distinguish stain types. RESULTS: According to the results of data training and comparison, all the recognition accuracies of Fanta^®, coffee, saliva and blood were more than 91.39%. Among them, saliva reached 100% recognition accuracy. CONCLUSIONS Three-dimensional fluorescence spectroscopy is a potential method for rapid and nondestructive identification of biological and non-biological stains.
Humans ; Forensic Medicine/methods* ; Coloring Agents/analysis* ; Coffee ; Spectrometry, Fluorescence ; Body Fluids/chemistry*

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective: To investigate the effects of aerobic exercise on non-alcoholic fatty liver (NAFLD) induced by high fat and the mechanism of CNPY2-PERK pathway. Methods: Eight-week-old male C57BL/6J mice were randomly divided into four groups: the control group (C), the C+ aerobic exercise group (CE), the model group (M) and the M+ aerobic exercise group (ME). Mice in group C and CE were given normal diet, while mice in group M and ME were given high-fat diet (60 cal % fat). The mice were fed continuously for 18 weeks until the end of the experiment, and the serum and liver samples were collected. Both CE and ME group performed an aerobic treadmill training from the 10th week (12 m/min, 60 min/ day, 5 days/week, for 8 weeks). The serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), alanine aminotransferase (ALT), aspartate aminotransferase (AST) were detected. The pathological morphology of the liver was observed. The relative expressions of CNPY2, PERK, p-eIF2a, CHOP, CNPY2 mRNA and PERK mRNA, and the positive expressions of CNPY2 and PERK were measured. Results: Compared with group C, the serum levels of LDL-c, TC, TG, ALT and AST in group M were increased significantly (P＜0.05), while the HDL-c level was decreased significantly (P＜0.05). The liver tissues of mice showed obvious hepatic steatosis, the number of lipid droplets in liver cells was increased, and the expressions of CNPY2, CNPY2mRNA, PERK, PERKmRNA, p-eIF2a, CHOP, and the positive expressions of both CNPY2 and PERK in liver were increased (P＜0.05). However, the above indexes showed no significant difference in CE group (P＞0.05). Compared with group M, the serum levels of LDL-c, TC, TG, ALT and AST in group ME were decreased (P＜0.05). The fatty degeneration of liver tissue and the number of lipid droplets in liver cells in mice was reduced, and the expressions of CNPY2, CNPY2 mRNA, PERK, PERK mRNA, p-eIF2a, CHOP, and the positive expressions of CNPY2 and PERK in liver tissue were decreased (P＜0.05). Conclusion: The CNPY2-PERK pathway is involved in the formation of NAFLD. Aerobic exercise can effectively ameliorate NAFLD, and the mechanisms may be related to the reduction of CNPY2-PERK pathway-related molecule expressions by aerobic exercise.
Animals ; Cholesterol, LDL ; Exercise ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease ; RNA, Messenger ; Triglycerides

OBJECTIVE: To explore the early clinical efficacy of primary total hip arthroplasty(THA) with Corail standard stems (KS type) and high offset stems (KHO type), by analyzing the postoperative radiographic parameters of different offset of femoral components with Corail stem which has a neck-shaft angle of 135 ° in unilateral primary THA, by comparing the measurement results on both sides and analyzing the reconstruction of the postoperative femoral offset and the hip joint function recovery. METHODS: A retrospective analysis was made of 186 patients with unilateral hip joint lesions who underwent the first total hip arthroplasty with Johnson & Johnson Corail prostheses from January 2015 to June 2017. According to the use of femoral prostheses with different eccentricities during the operation, the patients were divided into high eccentricity group and standard eccentricity group. In the high eccentricity group, there were 52 cases of Corail high eccentricity prosthesis(KHO type), including 20 females and 32 males;aged 21 to 71 years old with an average of(50.6±13.2) years;body mass index(BMI) was (26.0±4.1) kg/m². The standard eccentricity group included 134 Corail standard femoral stem prostheses(KS type), 57 females and 77 males;aged 18 to 77 years old with an average of (47.3±14.0) years;BMI was (25.3±3.5) kg/m². The abduction arm, femoral eccentricity, acetabular eccentricity and the length difference of lower limbs were measured on the postoperatively positive X-ray film of the hip joint. Harris score and related complications were recorded before and after the operation, and the stability of the prosthesis was analyzed. RESULTS: There were significant differences in femoral eccentricity, joint eccentricity and abduction arm between the affected side and the healthy side in the high eccentricity group(P<0.05). There were significant differences in femoral eccentricity and acetabular eccentricity between the affected side and the healthy side in the standard eccentricity group(P<0.05). There were significant differences in combined eccentricity, abduction arm and length of lower limbs between two groups(P<0.05). In the high eccentricity group, the abduction arm of the affected hip joint was positively correlated with the femoral eccentricity, acetabular eccentricity and joint eccentricity(r=0.633, P<0.001;r=0.384, P=0.005;r=0.690, P<0.001). The same results were also obtained in the healthy side(r=0.688, P<0.001;r=0.574, P<0.001;r=0.765, P<0.001). In the standard eccentricity group, the abduction arm of the affected hip joint was positively correlated with the femoral eccentricity, acetabular eccentricity and combined eccentricity(r=0.734, P<0.001;r=0.418, P<0.001;r=0.749, P<0.001). The same results were also obtained in the healthy side(r=0.775, P<0.001;r=0.397, P<0.001;r=0.773, P<0.001). The difference of the length of both lower limbs was significantly correlated with the difference of bilateral joint eccentricity and bilateral abduction arm (r=0.376, P=0.006;r=-0.346, P=0.012). There was no significant correlation between the difference of the length of both lower limbs and the difference of bilateral joint eccentricity and bilateral abduction arm (r=-0.009, P=0.919;r=-0.036, P=0.682). There was no significant difference in Harris score between two groups at the last follow-up(P>0.05). At the last follow-up, Trendelenburg was negative in all patients in both groups, and the prostheses were stable. CONCLUSION Both Corail standard stem and high offset stem may be effectively reconstruct the femoral offset, reconstruct the anatomical structure and biomechanics of the hip joint, and maintain the length of lower limbs and the stability of the hip joint in the unilateral primary total hip arthroplasty. Although the offset of the femur was not reconstructed normally in some cases, the stability of the components and postoperative function were not affected.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Adolescent ; Arthroplasty, Replacement, Hip/methods* ; Retrospective Studies ; Hip Prosthesis ; Femur/surgery* ; Lower Extremity

OBJECTIVES: To develop the birth weight curve of twin neonates with a gestational age of 25-40 weeks, and to investigate the regional differences of the birth weight curve. METHODS: A total of 11 maternal and child health care hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Liuzhou, Guilin, Quanzhou, Shenzhen, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live twin neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves. RESULTS: A total of 17 256 twin neonates with a gestational age of 25-40 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities in China were established, and the birth weight percentile curves were drawn. The birth weight curve level of twin neonates in Liuzhou was lower than the average level of the 11 cities; the birth weight curve level of twin neonates in Ningbo was higher than the average level of the 11 cities; the birth weight curve level of twin neonates in Lianyungang was obviously higher than the average level of the 11 cities; the birth weight curve level of twin neonates in other 8 cities was almost the same as the average level of the 11 cities. CONCLUSIONS The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of twin neonates in the region. The level of intrauterine growth of twin neonates in some cities is different from the average level of the 11 cities of China.
Birth Weight ; Child ; China ; Cities ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Twins

OBJECTIVES: To develop the birth weight curves of the Chinese Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, as well as the birth weight means of full-term neonates of 14 Chinese ethnic groups. METHODS: The live singleton neonates who were born in 11 maternal and child health care hospitals from 11 cities of China between January 2017 and December 2020 were classified according to the mother's ethnic group. Birth weight means were calculated for the full-term neonates of each ethnic group. For the Han and Zhuang singleton neonates with a large sample size, the Lambda-Mu-Sigma (LMS) method was used to establish the birth weight percentile curves of the Han and Zhuang singleton neonates with different gestational ages. RESULTS: A total of 105 365 live singleton neonates were included, among whom the Han neonates had the highest number of 84 851 (26-41 weeks of gestation), followed by the Zhuang neonates (12 803 neonates with a gestational age of 28-41 weeks). The neonates of the other Chinese ethnic groups enrolled were live full-term singleton neonates, with a sample size of more than 100 neonates for each ethnic group. The 3rd-97th percentile curves of birth weight were established for the Han singleton neonates with a gestational age of 26-41 weeks and the Zhuang singleton neonates with a gestational age of 28-41 weeks. The birth weight curves of the Han singleton neonates at each gestational age were higher than those of the Zhuang singleton neonates. Birth weight means (3 199-3 499 g) and standard deviations were determined for 14 Chinese ethnic groups, i.e., Li, Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. The Li ethnic group had the lowest birth weight, followed by the Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. CONCLUSIONS The 3rd-97th percentile curves of birth weight are developed for the Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, and birth weight means are determined for the full-term neonates of 14 Chinese ethnic groups in 11 cities of China, which provides a reference for evaluating the intrauterine growth of neonates in these ethnic groups.
Infant, Newborn ; Male ; Child ; Humans ; Infant ; Birth Weight ; Ethnicity ; Cities ; Gestational Age ; China

OBJECTIVE: To investigate the expression of MC1R in esophageal squamous cell carcinoma and its correlation with the clinicopathological parameters. METHODS: We analyzed the expression of MC1R in esophageal cancer based on data from TCGA databse and examined its expression levels using RT-PCR and Western blotting in a human esophageal epithelial cell line BAr-T, human esophageal squamous cell carcinoma cell lines ECA109, KYSE30, KYSE150, KYSE510, TE-1, TE-13, and EC9706, a human gastric cancer cell line SGC7901 and 19 pairs of esophageal squamous cell carcinoma tissues and adjacent tissues.Immunohistochemistry was used to detect MC1R expression levels in 32 pairs of paraffin-embedded sections of esophageal squamous cell carcinoma and adjacent tissues, and the correlation of MC1R expression and the patients'clinicopathological characteristics was analyzed. RESULTS: Bioinformatics analysis showed that MC1R was significantly overexpressed in esophageal cancer tissues (P < 0.05).MC1R expression was also increased in 5 esophageal squamous cell carcinoma cell lines ECA109, KYSE30, KYSE510, TE-13, EC9706 and the gastric cancer cell line SGC7901 as compared with that in esophageal epithelial cells (P < 0.05).Immunohistochemistry revealed significantly increased MC1R expression in esophageal squamous cell carcinoma tissue sections in comparison with the adjacent tissue sections (P < 0.05).In patients with esophageal squamous cell carcinoma, a high MC1R expression was detected mainly in those with an old age, positive for middle-thoracic involvement, and with moderately differentiated tumor cells, and showed a correlation with T stage of tumor (P < 0.05), but not with the other clinicopathological parameters such as gender, age, degree of cell differentiation, primary tumor site, or TNM stage (P>0.05). CONCLUSION MC1R is highly expressed in esophageal squamous cell carcinoma and may serve as a molecular biomarker to assist in the diagnosis of esophageal squamous cell carcinoma.
Humans ; Esophageal Squamous Cell Carcinoma ; Esophageal Neoplasms/metabolism* ; Stomach Neoplasms ; Cell Line, Tumor ; Immunohistochemistry ; Cell Proliferation ; Gene Expression Regulation, Neoplastic

This paper established the identification technology of the main root origin of three-year-old spring Panax notoginseng aiming at providing theoretical basis for the protection and traceability of geographical indication products of P. notoginseng. Forty-four samples of three-year-old spring P. notoginseng from Guangxi Baise, Yunnan Wenshan, Yunnan new cultivating regions. The stable isotopic ratios of carbon, nitrogen, hydrogen and oxygen were determined by elemental analysis and stable isotope mass spectrometer. Combined with Duncan multiple comparative analysis, fisher discriminant analysis and sequential discriminant analysis, a origin discriminant model for the main root of three-year-old spring P. notoginseng was established for 3 production areas of P. notoginseng. The geographical climate and environment of three production areas of P. notoginseng are obviously different. From Guangxi Baise-Yunnan Wenshan-Yunnan new cultivating regions, the longitude, average annual temperature and annual precipitation gradually decrease, and the elevation and latitude are increasing. The results of multiple comparative analysis showed that there were significant or very signi-ficant differences in the δ~(13)C,δ~(15)N,δ~2H,δ~(18)O of the main roots of P. notoginseng in three regions. The results of fisher's discriminant analysis and sequential discriminant analysis showed that the correct discriminant rates of the main roots of P. notoginseng for three regions were 80.05%,76.47% and 90.91%, respectively, based on four stable isotope ratios, with an average of 84.09%. Using stable isotope fingerprint and chemometrics method, we can distinguish the origin of the main raw materials and products of P. notoginseng.
China ; Geography ; Isotopes ; Panax notoginseng ; Seasons