Based on ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap high-resolution mass spectrometry(UPLC-Q-Orbitrap HRMS) technology and molecular docking, the bitter-tasting substances(hereafter referred to as "bitter substances") in Cistanche deserticola extract were investigated, and the bitter taste and efficacy relationship was explored to lay the foundation for future research on de-bittering and taste correction. Firstly, UPLC-Q-Orbitrap HRMS was used for the qualitative analysis of the constituents of C. deserticola, and 69 chemical components were identified. These chemical components were then subjected to molecular docking with the bitter taste receptor, leading to the screening of 20 bitter substances, including 6 phenylethanol glycosides, 5 flavonoids, 3 phenolic acids, 2 cycloalkenyl ether terpenes, 2 alkaloids, and 2 other components. Nine batches of fresh C. deserticola samples were collected from the same origin but harvested at different months. These samples were divided into groups based on harvest month and plant part. The bitterness was quantified using an electronic tongue, and the content of six potential bitter-active compounds(pineconotyloside, trichothecene glycoside, tubulin A, iso-trichothecene glycoside, jinshihuaoside, and jingnipinoside) was determined by high-performance liquid chromatography(HPLC). The total content of phenylethanol glycosides, polysaccharides, alkaloids, flavonoids, and phenolic acids was determined using UV-visible spectrophotometry. Chemometric analyses were then conducted, including Pearson's correlation analysis, gray correlation analysis, and orthogonal partial least squares discriminant analysis(OPLS-DA), to identify the bitter components in C. deserticola. The results were consistent with the molecular docking findings, and the two methods mutually supported each other. Finally, network pharmacological predictions and analyses were performed to explore the relationship between the targets of bitter substances and their efficacy. The results indicated that key targets of the bitter substances included EGFR, PIK3CB, and PTK2. These substances may exert their bitter effects by acting on relevant disease targets, confirming that the bitter substances in C. deserticola are the material basis of its bitter taste efficacy. In conclusion, this study suggests that the phenylethanol glycosides, primarily pineconotyloside, mauritiana glycoside, and gibberellin, are the material basis for the "bitter taste" of C. deserticola. The molecular docking technique plays a guiding role in the screening of bitter substances in traditional Chinese medicine(TCM). The bitter substances in C. deserticola not only contribute to its bitter taste but also support the concept of the "taste-efficacy" relationship in TCM, providing valuable insights and references for future research in this area.
Molecular Docking Simulation ; Taste ; Chromatography, High Pressure Liquid ; Cistanche/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Mass Spectrometry

OBJECTIVE: To compare the short-term clinical efficacy and safety of closed reduction with Kirschner wire fixation versus open reduction with plate fixation for treating osteoporotic Colles' fractures in middle-aged and elderly patients. METHODS: Between January 2018 and January 2023, 119 patients with Colles fractures were retrospectively analyzed, including 39 males and 80 females, aged from 48 to 74 years old with an average of(60.58±6.71) years old. The time from injury to operation ranged 1 to 13 days with an average of (5.29±2.52) days. According to the surgical method, they were divided into Kirschner wire fixation group (Kirschner wire group) and plate internal fixation group (plate group). In Kirschner wire group, there were a total of 68 patients, comprising 21 males and 47 females. The average age was (61.15±6.24) years old, ranged from 49 to 74 years old. Among them, 41 cases involved the left side while 27 cases involved the right side. In the plate group, there were a total of 51 patients, including 18 males and 33 females. The average age was (59.78±5.71) years old ranged from 48 to 72 years old. Among them, there were 31 cases on the left side and 20 cases on the right side. The following parameters were recorded before and after the operation:operation time, intraoperative blood loss, hospitalization days, hospitalization expenses, postoperative complications, and radiographic parameters of distal radius (distal radius height, ulnar deviation angle, palmar tilt angle). The clinical efficacy was evaluated at 3 and 12 months after the operation using Gartland-Werley and disabilites of the arm shoulder and hand (DASH) scores. RESULTS: The patients in both groups were followed up for a duration from 12 to 19 months with an average of(13.32±2.02) months. The Kirschner wire group exhibited significantly shorter operation time compared to the plate group 27.91(13.00, 42.00) min vs 67.52(29.72, 105.32) min, Z=-8.74, P=0.00. Intraoperative blood loss was also significantly lower in the Kirschner wire group than in the plate group 3.24(1.08, 5.40) ml vs 21.91(17.38, 26.44) ml, Z=-9.31, P=0.00. Furthermore, patients in the Kirschner wire group had a shorter length of hospital stay compared to those in the plate group (8.38±2.63) days vs (11.40±2.78) days, t=-3.12, P=0.00. Additionally, hospitalization cost was significantly lower in the Kirschner wire group than in the plate group 10 111.29(6 738.98, 13 483.60) yuan vs 15 871.11(11 690.40, 20 051.82) yuan, Z=-5.62, P=0.00. The incidence of complications was 2 cases in the Kirschner wire group and 1 case in the plate group, with no statistically significant difference(P>0.05). At 3 months postoprative, the radial height of the Kirschner wire group was found to be significantly smaller than that of the plate group, with measurements of (11.45±1.69) mm and (12.11±1.78) mm respectively (t=-2.06, P=0.04). However, there were no statistically significant differences observed in ulnar deviation angle and palmar tilt angle between the two groups (P>0.05). The DASH score and Gartland-Werley score in the Kirschner group were significantly higher than those in the plate group at 3 months post-operation (19.10±9.89) vs (13.47±3.51), t=4.34, P=0.00;(11.15±3.61) vs (6.41±2.75), t=8.13, P=0.00). However, there was no significant difference between the two groups at 12 months post-operation (P>0.05). CONCLUSION Compared to plate internal fixation, closed reduction with Kirschner wire support fixation yields a slightly inferior recovery of radial height;however, there is no significant disparity in the functional score of the affected limb at 12 months post-operation. Nonetheless, this technique offers advantages such as shorter operation time, reduced intraoperative blood loss, decreased hospitalization duration, and lower cost.
Humans ; Female ; Male ; Middle Aged ; Aged ; Fracture Fixation, Internal/instrumentation* ; Bone Wires ; Bone Plates ; Retrospective Studies ; Colles' Fracture/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Open Fracture Reduction/methods* ; Osteoporotic Fractures/surgery*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective:To investigate the clinical benefit and application value of the Da Vinci robotic surgical system through bilateral axillary areolar approach in cervical lymph node dissection in obese thyroid carcinoma patients.Methods:The clinical data of 117 patients with thyroid cancer admitted to the thyroid and breast surgery Department of the 960th Hospital of the Chinese PLA Joint Logistic Support Force from January 2018 to June 2023 were retrospectively analyzed. There were 55 males and 62 females, aged from 17 to 64 years, with an average age of (36.05±8.77) years. According to body mass index (BMI), patients were divided into normal group (18.5 kg/m 2≤BMI< 24 kg/m 2, n=60) and obese group (BMI≥28 kg/m 2, n=57). Gender, age, BMI, operation time, postoperative drainage fluid volume, tumor diameter, central lymph node dissection and number of metastasis, cervical lymph node dissection and number of metastasis, postoperative hospital stay, postoperative aesthetic satisfaction score and surgical complications of the two groups were analyzed. SPSS 26.0 statistical software was used to analyze the data. Results:All of patients completed the operation successfully, and neither group was transferred to open surgery. The BMI of obese group was higher than that of normal group [(31.35±3.08) kg/m 2vs (22.53±0.82) kg/m 2, t=20.97, P<0.05]. The maximum tumor diameter in the obese group was greater than that in the normal group [(13.81±10.70) mm vs (10.42±5.53) mm, t=2.17, P<0.05]. There were no significant differences in operation time, number of central lymph node dissection and metastasis, number of cervical lymph node dissection and metastasis and postoperative complications between the two groups ( P>0.05). Conclusions:Utilization of the Da Vinci robotic surgical system via the BABA approach demonstrates both safety and feasibility in obese patients with thyroid carcinoma undergoing lateral cervical lymph node dissection. Importantly, this technique does not increase the risk of surgical complications, thus providing a novel alternative for lateral cervical lymph node dissection in obese thyroid carcinoma patients.

Objective To explore the mechanism of somatostatin in improving acute lung injury associated with acute pancreatitis.Methods Wistar rats were randomly divided into sham operation group(injection of normal saline),model group(puncture of common bile duct and injection of 5％sodium taurocholate with wire ligation),somatostatin group(injection of somatostatin into tail vein of model group),somatostatin+miR-146a-5p inhibitor group(on the basis of somatostatin group,tail vein injection of miR-146a-5p inhibitor and somatostatin+oe-angiogenin-like protein 4(ANGPTL4)group(on the basis of somatostatin group,tail vein injection of oe-ANGPTL4 plasmid).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of pancreatic and lung tissues;pathological score and tissue wet-dry weight ratio were determined,real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect miR-146a-5p and ANGPTL4 mRNA expression and Western blot was used to detect the expression of related proteins in lung tissues of rats.Tumor necrosis factor-α(TNF-α)was detected by enzyme-linked immunosorbent assay(ELISA).Results In sham operation group,model group and somatostatin group,the damage degree of pancreas tissue(based on modified computed tomography severity index)were 1.25±0.28,3.20±0.34,2.15±0.31,respectively;the damage degree of lung tissue(based on the Smith lung injury score system)were 1.40±0.13,5.10±0.58,3.10±0.38,respectively.The relative expression levels of ANGPTL4 mRNA in sham operation group,model group,somatostatin group and somatostatin+miR-146a-5p inhibitor group were 1.00±0.17,1.63±0.20,1.21±0.18 and 1.73±0.28.The levels of TNF-α in sham operation group,model group,somatostatin group,somatostatin+miR-146a-5p inhibitor group and somatostatin+oe-ANGPTL4 group were(76.33±7.25),(125.05±13.56),(80.11±10.68),(118.62±14.32)and(105.32±13.52)pg·mL-1,respectively;the relative expression levels of nuclear factor E2-related factor 2(Nrf2)protein were 1.00±0.27,0.51±0.07,0.88±0.14,0.68±0.12,0.51±0.09,respectively;the relative expression levels of heme oxygenase-1(HO-1)protein were 1.00±0.25,0.58±0.11,0.79±0.18,0.48±0.07 and 0.50±0.08,respectively.The above indexes of the model group were compared with those of the sham operation group,and the above indexes of the somatostatin group were compared with those of the model group,somatostatin+miR-146a-5p inhibitor group and somatostatin+oe-ANGPTL4 group,and the differences were statistically significant(all P＜0.05).Conclusion Somatostatin has antioxidant and anti-inflammatory effects and can ameliorate acute lung injury associated with acute pancreatitis.The mechanism may be related to Nrf2/HO-1 pathway mediated by miR-146a-5p/ANGPTL4.

Objective:To investigate the relationship between intramuscular adipose tissue index (IATI) calculated from computed tomography images at transverse process of the first lumbar and all-cause mortality in maintenance dialysis patients, and to provide a reference for improving the prognosis in these patients.Methods:It was a multicenter retrospective cohort study. The clinical data of patients who received maintenance hemodialysis or peritoneal dialysis treatment from January 1, 2017 to December 31, 2019 in 4 grade Ⅲ hospitals including Zhongda Hospital Affiliated to Southeast University, Taizhou People's Hospital Affiliated to Nanjing Medical University, Affiliated Hospital of Yangzhou University, and the Third Affiliated Hospital of Soochow University were retrospectively collected. IATI was calculated by low attenuation muscle (LAM) density/skeletal muscle density. The receiver-operating characteristic curve was used to determine the optimal cut-off value of IATI, and the patients were divided into high IATI group and low IATI group according to the optimal cut-off value. The differences of baseline clinical data and measurement parameters of the first lumbar level between the two groups were compared. The follow-up ended on December 23, 2022. The endpoint event was defined as all-cause mortality within 3 years. Kaplan-Meier survival curve and log-rank test were used to analyze the survival rates and the differences between the two groups. Multivariate Cox regression analysis models were used to analyze the association between IATI and the risk of all-cause mortality in maintenance dialysis patients. Multivariate logistic regression analysis model was used to analyze the influencing factors of high IATI.Results:A total of 478 patients were eligibly recruited in this study, with age of (53.55±13.19) years old and 319 (66.7%) males, including 365 (76.4%) hemodialysis patients and 113 (23.6%) peritoneal dialysis patients. There were 376 (78.7%) patients in low IATI (<0.42) group and 102 (21.3%) patients in high IATI (≥0.42) group. The proportion of age ≥ 60 years old ( χ2=24.746, P<0.001), proportion of diabetes mellitus ( χ2=5.570, P=0.018), fasting blood glucose ( t=-2.145, P=0.032), LAM density ( t=-3.735, P<0.001), LAM index ( t=-7.072, P<0.001), and LAM area/skeletal muscle area ratio ( Z=-9.630, P<0.001) in high IATI group were all higher than those in low IATI group, while proportion of males ( χ2=11.116, P<0.001), serum albumin ( Z=2.708, P=0.007) and skeletal muscle density ( t=12.380, P<0.001) were lower than those in low IATI group. Kaplan-Meier survival analysis showed that the 3-years overall survival rate of low IATI group was significantly higher than that in high IATI group (Log-rank χ2=19.188, P<0.001). Multivariate Cox regression analysis showed that IATI<0.42 [<0.42/≥0.42, HR(95% CI): 0.50 (0.31-0.83), P=0.007] was an independent protective factor of all-cause mortality, and age ≥60 years old [ HR (95% CI): 2.61 (1.60-4.23), P<0.001], diabetes mellitus [ HR (95% CI): 1.71 (1.06-2.78), P=0.029] and high blood neutrophil/lymphocyte ratio [ HR (95% CI): 1.04 (1.00-1.07), P=0.049] were the independent risk factors of all-cause mortality in maintenance dialysis patients. Stepwise Cox regression analysis showed that IATI<0.42 was still an independent protective factor of all-cause mortality in maintenance dialysis patients [<0.42/≥0.42, HR (95% CI): 0.45 (0.27-0.76), P=0.003]. Multivariate logistic regression analysis showed that low skeletal muscle density [ OR (95% CI): 0.84 (0.81-0.88), P<0.001] and high serum triglyceride [ OR (95% CI): 1.39 (1.07-1.82), P=0.015] were the independent influencing factors of IATI≥0.42. Conclusion:IATI<0.42 of the first lumbar level is an independent protective factor of all-cause mortality in maintenance dialysis patients. Localized myosteatosis within high-quality skeletal muscle may reduce the risk of all-cause mortality in these patients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

【Objective】 To analyze the correlation between the expressions of CD10,CA9 and CD133 and the prognosis of patients with metastatic renal clear cell carcinoma (mccRCC) treated with sorafenib or sunitinib. 【Methods】 A total of 80 mccRCC patients who received sorafenib or sunitinib as first-line therapy were retrospectively enrolled. Immunohistochemical staining (IHC) was performed for CD10,CA9 and CD133 in tumor tissue samples to analyze the correlation between the expression of each marker and clinicopathologic variables. Univariate and multivariate Cox proportional risk models were used to analyze prognostic factors of progression free survival (PFS) and overall survival (OS),and Kaplan-Meier survival analysis was performed for CA9 expression and PFS,OS in the treatment subgroups. 【Results】 Altogether 37 patients (46.25%) had PFS,and the median PFS (mPFS) was 24.9 months (95%CI:16.5-33.2 months),while 55 patients (68.75%) died and the median OS (mOS) was 44.2 months (95%CI:14.6-73.7). Low expression of CD10 was correlated with high Fuhrman grade (χ²=6.241,P=0.012),lymph node metastasis (χ²=5.952,P=0.015),and the number of metastatic organs ≥2 (χ²=8.205,P=0.004). Univariate analysis showed that Fuhrman grade,number of metastatic organs and lymph node metastasis were the prognostic factors of PFS (P<0.05),while the number of metastatic organs,lymph node metastasis and CA9 expression were the prognostic factors of OS (P<0.05). Multivariate analysis showed that Fuhrman grade was an independent factor of PFS (HR=2.457,95%CI:1.126-5.365,P=0.024),and the number of metastatic organs was an independent prognostic factor of OS (HR=1.857,95%CI:1.048-3.290,P=0.034). Survival analysis in subgroups showed that high CA9 expression in the sorafenib group was associated with longer OS (HR=0.401,95%CI:0.204-0.787,P=0.008). 【Conclusion】 Low expression of CA9 is an non-independent risk factor for OS,while CD10 and CD133 cannot be used as prognostic factors for mccRCC patients. Since mccRCC patients with low CA9 expression have less survival benefit from sorafenib and sunitinib,they can choose target therapy combined with immunotherapy or dual immunotherapy according to the guidelines to improve prognosis.

Objective:To learn about the progress of prevention and control of drinking-water-borne endemic arsenic poisoning in Henan Province, and provide scientific basis for achieving the goal of eliminating high arsenic hazards as scheduled.Methods:From July to August 2019, in accordance with the requirements of the National Monitoring Program for Drinking-water-borne Endemic Arsenic Poisoning, a general survey was carried out in 26 high-arsenic villages in 6 counties of Henan Province to investigate the water improvement situation and the operation of water improvement projects, and the arsenic content in drinking water of households was measured, meanwhile, the arsenic poisoning status of permanent residents in high-arsenic villages was investigated.Results:All 26 villages with high arsenic content in the province had undergone water improvement, with a water improvement rate of 100.00%. A total of 18 water improvement projects were investigated in 26 high-arsenic villages, all of which were operating normally. Twenty-six water samples were collected, and the arsenic content in the household water was < 0.01 mg/L, which met the sanitary standards for drinking water. No patient of endemic arsenic poisoning was found during the survey.Conclusion:In Henan Province, the drinking-water-borne endemic arsenic poisoning has been effectively controlled, and the prevention and control achievements should continue to be consolidated in the future.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.