GCN5 mediates DNA-PKcs crotonylation for DNA double-strand break repair and determining cancer radiosensitivity.

BACKGROUND: DNA double-strand break (DSB) induction and repair are important events for determining cell survival and the outcome of cancer radiotherapy. The DNA-dependent protein kinase (DNA-PK) complex functions at the apex of DSBs repair, and its assembly and activity are strictly regulated by post-translation modifications (PTMs)-associated interactions. However, the PTMs of the catalytic subunit DNA-PKcs and how they affect DNA-PKcs's functions are not fully understood. METHODS: Mass spectrometry analyses were performed to identify the crotonylation sites of DNA-PKcs in response to γ-ray irradiation. Co-immunoprecipitation (Co-IP), western blotting, in vitro crotonylation assays, laser microirradiation assays, in vitro DNA binding assays, in vitro DNA-PK assembly assays and IF assays were employed to confirm the crotonylation, identify the crotonylase and decrotonylase, and elucidate how crotonylation regulates the activity and function of DNA-PKcs. Subcutaneous xenografts of human HeLa GCN5 WT or HeLa GCN5 siRNA cells in BALB/c nude mice were generated and utilized to assess tumor proliferation in vivo after radiotherapy. RESULTS: Here, we reveal that K525 is an important site of DNA-PKcs for crotonylation, and whose level is sharply increased by irradiation. The histone acetyltransferase GCN5 functions as the crotonylase for K525-Kcr, while HDAC3 serves as its dedicated decrotonylase. K525 crotonylation enhances DNA binding activity of DNA-PKcs, and facilitates assembly of the DNA-PK complex. Furthermore, GCN5-mediated K525 crotonylation is indispensable for DNA-PKcs autophosphorylation and the repair of double-strand breaks in the NHEJ pathway. GCN5 suppression significantly sensitizes xenograft tumors of mice to radiotherapy. CONCLUSIONS: Our study defines K525 crotonylation of DNA-PKcs is important for the DNA-PK complex assembly and DSBs repair activity via NHEJ pathway. Targeting GCN5-mediated K525 Kcr of DNA-PKcs may be a promising therapeutic strategy for improving the outcome of cancer radiotherapy.

Endolichenic Fungi: A Promising Medicinal Microbial Resource to Discover Bioactive Natural Molecules-An Update.

Lichens are some of the most unique fungi and are naturally encountered as symbiotic biological organisms that usually consist of fungal partners (mycobionts) and photosynthetic organisms (green algae and cyanobacteria). Due to their distinctive growth environments, including hot deserts, rocky coasts, Arctic tundra, toxic slag piles, etc., they produce a variety of biologically meaningful and structurally novel secondary metabolites to resist external environmental stresses. The endofungi that live in and coevolve with lichens can also generate abundant secondary metabolites with novel structures, diverse skeletons, and intriguing bioactivities due to their mutualistic symbiosis with hosts, and they have been considered as strategically significant medicinal microresources for the discovery of pharmaceutical lead compounds in the medicinal industry. They are also of great importance in the fundamental research field of natural product chemistry. In this work, we conducted a comprehensive review and systematic evaluation of the secondary metabolites of endolichenic fungi regarding their origin, distribution, structural characteristics, and biological activity, as well as recent advances in their medicinal applications, by summarizing research achievements since 2015. Moreover, the current research status and future research trends regarding their chemical components are discussed and predicted. A systematic review covering the fundamental chemical research advances and pharmaceutical potential of the secondary metabolites from endolichenic fungi is urgently required to facilitate our better understanding, and this review could also serve as a critical reference to provide valuable insights for the future research and promotion of natural products from endolichenic fungi.

Hemodynamic changes and perinatal outcome associated with umbilical artery thrombosis: a retrospective study.

OBJECTIVE: Poor fetal and perinatal outcomes in fetuses associated with umbilical artery thrombosis (UAT), such as severe intrauterine growth restriction (IUGR) and intrauterine asphyxia have been reported by some case series. Its hemodynamic impact remains unclear. The aim of this study was to evaluate the hemodynamic changes and perinatal outcome in UAT fetuses with a relatively large sample. METHODS: We included singleton fetuses diagnosed with UAT and with at least one available Doppler evaluation before the end of pregnancy in our center from 2016 to 2023. Fetuses with structural abnormalities and with no follow-up results were excluded. Doppler waveforms from the Umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and uterine artery (UtA) were routinely evaluated according to ISUOG Practice Guidelines from diagnosis. The same sample of GA-matched normal fetuses with Doppler measurements during the same period were randomly selected as control group. RESULTS: Eighty-nine singleton fetuses with UAT with at least one Doppler evaluation before the end of pregnancy were identified, 13 fetuses with no follow-up results were excluded. After comprehensive prenatal counseling, 14 cases received urgent cesarean section, the remaining 55 cases received expectant management, the median day between GA at diagnosis and end of pregnancy was 13 (5-53) days (range, 2-159). 7 (7/76, 9.2%) cases occurred stillbirth, and the incidence of IUGR and Neonatal Intensive Care Unit (NICU) admission were 18.4% (14/76) and 13.2% (10/76) respectively. 49 fetuses (49/76, 64.5%) combined with Doppler abnormalities. UA abnormalities (35/76, 46.1%) and MCA abnormalities (34/76, 44.7%) were the most changes at presentation. Compared to control group, UA-EDV was significantly increased in UAT fetuses [21.84 (15.59-26.64) vs. 16.40 (12.43-20.70) cm/s, p < 0.001], UA-PI and UA-RI significantly decreased [0.68 (0.57-0.84) vs. 0.92 (0.79-1.11), p<0.001; 0.51 (0.44-0.59) vs. 0.62 (0.55-0.68), p < 0.001, respectively]. Both the MCA-PSV and MCA-EDV were significantly higher in UAT fetuses [54.60 (48.00-61.34) vs. 44.47 (29.66-57.60) cm/s, p < 0.001; 11.19 (7.84-17.60) vs. 8.22 (5.21-12.00) cm/s, p < 0.001, respectively], this led to a lower MCA-PI and MCA-RI. Meanwhile, DV-PIV was significantly higher in UAT fetuses [0.6 (0.47-0.87) vs. 0.45 (0.37-0.55), p < 0.001], CPR and UtA-PI were no significant difference between these two groups. Multivariate logistic regression analysis showed that DV-PIV was an independent risk factor for adverse pregnancy outcomes (OR 161.922, p<0.001), the area under the ROC curve (AUC) was 0.792 (95% CI 0.668-0.917; p < 0.001). CONCLUSION: Our data showed serious adverse pregnancy consequences are combined with UAT fetuses. Hemodynamic changes in UAT fetuses showed the remaining artery for compensation and brain perfusion derangement. With a comprehensive and standardized Doppler evaluation, progression of fetal deterioration may be detailed presented.

Light-Mediated Multilevel Flexible High-Efficiency Perovskite Resistive Switching Memory Based on Mn:CsPbCl3 Nanocrystals.

Herein, the electrical characteristics, photoelectric properties, resistive switching (RS) mechanism, and flexible storage application of Ag/PMMA&Mn:CsPbCl3/ITO (PMMA = poly(methyl methacrylate)) devices are studied by using the photoelectric material Mn:CsPbCl3 nanocrystals (NCs) embedded in PMMA as the RS layer. The devices exhibit bipolar RS behavior with low operating voltage, excellent cycling endurance (>1000 times), long retention time (≥104 s), high ON/OFF ratio (≈104), and good environmental stability. The flexible memory devices have demonstrated reliable mechanical stability of consecutive 1000 bending cycles. In addition, multilevel data storage is realized by introducing the UV light, and the adjustive resistive switching characteristics is achieved through photoelectric synergistic work. The resistive switching mechanism under the excitation of light has been studied comprehensively. This work may pave a new way for developing the next generation of high-density data storage and photoelectric memristor.

Risk factors for malnutrition in patients with diabetic foot ulcer and its association with prolonged length of hospitalization.

PURPOSE: The study was designed to investigate the occurrence and risk factors of malnutrition in diabetic foot ulcers (DFU) patients and examine the association between malnutrition and length of stay (LOS). METHODS: This observational study included DFU hospitalized patients in two campuses of a hospital from January 2021 to June 2023. The diagnosis standard of malnutrition was established by using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Patients were followed up to ascertain the length of hospitalization, and hospital stays longer than 17 days were considered as prolonged LOS. To explore the risk factors of malnutrition and the association between malnutrition and LOS, univariate and multivariate logistic regression analyses were performed. RESULTS: Overall 219 DFU patients were enrolled, malnutrition was identified in 38.36% of patients according to GLIM criteria, and 92 patients (42%) were recognized as prolonged LOS. Logistic regression analyses showed that BMI (P <0.001), Alb (P = 0.002), HbA1c (P <0.001), ulcer infection (P <0.001), LOS (P = 0.010), and ABI (P = 0.024) were independent risk factors for malnutrition. Besides, malnutrition by GLIM criteria was closely related to prolonged LOS and malnourished DFU patients were 2.857 times (95% CI, 1.497-5.450; P = 0.001) likely to present prolonged LOS than that of normal nutrition. CONCLUSION: Malnutrition was considered to be extremely prevalent in DFU patients and was associated with approximately three times higher likelihood of prolonged LOS. Implementing and disseminating the diagnostic criteria during routine practice is crucial, given the predictive efficacy of GLIM criteria.

Protective effect of ginsenoside Rb1 against aconitine cardiotoxicity studied by myocardial injury, action potential, and calcium signaling.

Aconitine is the main active component of Aconitum plants. Although aconitine has effects that include strengthening the heart, analgesia, anti-tumor, and immune-regulating effects, aconitine has both efficacy and toxicity, especially cardiotoxicity. Severe effects can include arrhythmia and cardiac arrest, which limits the clinical application of aconitine-containing traditional Chinese medicine. Ginsenoside Rb1(Rb1) is mainly found in plants, such as ginseng and Panax notoginseng, and has cardiovascular-protective and anti-arrhythmia effects. This study aimed to investigate the detoxifying effects of Rb1 on aconitine cardiotoxicity and the electrophysiological effect of Rb1 on aconitine-induced arrhythmia in rats. Pathological analysis, myocardial enzymatic indexes, and Western blotting were used to investigate the ameliorating effect of Rb1 on aconitine cardiotoxicity. Optical mapping was used to evaluate the effect of Rb1 on action potential and calcium signaling after aconitine-induced arrhythmia. Rb1 inhibited pathological damage caused by aconitine, decreased myocardial enzyme levels, and restored the balance of apoptotic protein expression by reducing the expression of Bax and cleaved caspase 3 and increasing the expression of Bcl-2, thereby reducing myocardial damage caused by aconitine. Rb1 also reduced the increase in heart rate caused by aconitine, accelerated action potential conduction and calcium signaling, and reduced the dispersion of action potential and calcium signal conduction. Rb1 reduced the cardiotoxicity of aconitine by attenuating aconitine-induced myocardial injury and inhibiting the aconitine-induced retardation of ventricular action potential and calcium signaling in rats.

A Flexible Memristor Based on CsPbCl3 Nanocrystals for an Artificial Nociceptor.

Halide perovskites (HPs) based memristors show great potential in the simulation of biological neurons. Herein, a memristor with Ag/PMMA&CsPbCl3/ITO structure is developed by incorporating CsPbCl3 nanocrystals (NCs) into poly(methyl methacrylate) (PMMA) as the functional layer. The device exhibits typical bipolar resistive behavior, low operating voltage, good endurance of more than 400 cycles, consistent and excellent ON/OFF ratio (≈ 103), and high mechanical bending stability (bending times = 1000). The RS mechanism has been well explained by the electric field induced formation and rupture of Ag filaments in the PMMA&CsPbCl3 layer. More importantly, the memristor successfully displays fundamental nociceptive functions including threshold, nonadaptation, relaxation, and sensitization (allodynia and hyperalgesia). To demonstrate the feasibility of the artificial nociceptor, a pressure nociceptor system is constructed using the Ag/PMMA&CsPbCl3/ITO device. These results provide new perspectives for the development of next-generation, high-performance HPs based neural morphology devices.

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines.

BACKGROUND: Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown. AIM: To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. METHODS: Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. RESULTS: In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. CONCLUSION: We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.

Clinical observation of extremely elevated erythrocyte sedimentation rate / 中华危重病急救医学

Objective:To analyze the clinical features of adult patients with extremely elevated erythrocyte sedimentation rate (ESR, ESR≥100 mm/1 h), so as improve the ability of clinicians to use erythrocyte sedimentation rate to assist in the diagnosis and treatment of diseases.Methods:A retrospective cohort study was conducted to examine the clinical data of patients with ESR ≥ 100 mm/1 h admitted to the First Affiliated Hospital of Kunming Medical University from January 1st 2019 to December 31st 2019. The age, gender, clinical diagnosis, first ESR level after admission, blood routine, liver function, renal function, coagulation function and C-reactive protein (CRP) within 24 hours after admission were collected. Patient cohorts were divided into youth group (18-65 years old), middle-aged group (66-79 years old) and elderly group (≥80 years old) according to the new standards of human age classification of World Health Organization (WHO) 2019. Patient cohorts were also divided into infectious disease group, hematological disease group, autoimmune disease group, renal failure group and others according to their respective clinical diagnosis. The distribution of extremely elevated ESR in each group, and the correlation between ESR and various laboratory indicators were analyzed.Results:① Among 429 patients with ESR≥ 100 mm/1 h, there were 236 males and 193 females. There was no significant difference in ESR levels between males and females [mm/1 h: 108.00 (103.00, 119.75) vs. 117.00 (105.50, 140.00), P = 0.234]. ② The age of 429 patients ranged from 18 to 98 years old, the average age was (53.70±18.70) years old. There were 310 cases in the youth group, 87 cases in the middle-aged group and 32 cases in the elderly group. The ESR level of the young group was significantly lower than that of the middle-aged group and the elderly group [mm/1 h: 108.00 (103.00, 120.00) vs. 119.00 (107.00, 140.00), 120.00 (110.25, 140.00), both P < 0.01]. ③ The main diagnoses associated with extremely elevated ESR were infectious diseases [157 cases (36.6%)], hematological system diseases [127 cases (29.6%)], autoimmune diseases [74 cases (17.2%)]. Pulmonary infection accounted for 58.0% (91/157) of infectious diseases. Hematopoietic stem cell diseases accounted for 45.7% (58/127), lymphocyte and plasma cell diseases accounted for [37.0% (47/127)] and erythrocyte diseases accounted for [11.0% (14/127)] of the hematological system diseases. Diffuse connective tissue diseases accounted for 75.7% (56/74) of autoimmune diseases. ④ Spearman correlation analysis showed that the extremely elevated ESR in all patients was significantly negatively correlated with the levels of red blood cell count (RBC), hemoglobin (HB) and hematocrit (HCT) (ρvalue was -0.395, -0.381 and -0.383, respectively, all P < 0.01), the ESR was significantly positively correlated with the level of fibrinogen (FIB; ρ= 0.345, P < 0.01). A total of 266 patients were tested for both ESR and CRP, and there was no significantly correlation between ESR and CRP level (ρ= -0.019, P = 0.756). Conclusions:The extremely elevated ESR was more common in pulmonary infections diseases, hematopoietic stem cell diseases, lymphocyte and plasma cell diseases, erythrocyte diseases and diffuse connective tissue diseases. The extremely elevated ESR was significantly correlated with the levels of RBC, HB, HCT and FIB.

Adherence to adjuvant with therapy imatinib in patients with gastrointestinal stromal tumor: a national multi-center cross-sectional study / 中华胃肠外科杂志

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.

Clinical analysis of 32 adult patients with infection-associated hemophagocytic syndrome / 中华危重病急救医学

Objective:To analyze the clinical feature of adult patients with infection-associated hemophagocytic syndrome (IAHS), and to improve the ability of clinicians to diagnose and treat IAHS.Methods:A retrospectively study was performed. The clinical data of 32 adult patients with IAHS admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Kunming Medical University from July 2014 to November 2019 were analyzed. The general data, clinical manifestations, laboratory results, imaging findings, pathogen and clinical outcomes were collected, and the patients were divided into survival group and death group according to the 28-day prognosis. The clinical data between the two groups were compared, and multivariate Logistic regression analysis was used to analyze the variables with statistical significance in univariate analysis. The receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of variables with statistical significance in univariate analysis for 28-day prognosis of adult patients with IAHS.Results:Among 32 adult patients with IAHS, there were 17 males (53.1%) and 15 females (46.9%). Eighteen patients were bacterial infection, most of which were Acinetobacter baumannii and Escherichia coli; 14 patients were viral infection, mainly EB virus; and the overall 28-day mortality was 62.5% (20/32). ① Compared with the survival group ( n = 12), the levels of white blood cell (WBC), neutrocyte (NEU), lymphocyte (LYM), platelet (PLT) and oxygenation index (OI) in the death group ( n = 20) were lower, while the levels of aspartate aminotransferase (AST), K +, serum ferritin (SF) and lactate dehydrogenase (LDH) were higher [WBC (×10 9/L): 3.90±3.36 vs. 9.57±6.48, NEU (×10 9/L): 2.69±2.09 vs. 7.01±6.34, LYM (×10 9/L): 0.36 (0.23, 0.84) vs. 1.24 (0.61, 2.36), PLT (×10 9/L): 51.15±27.60 vs. 108.42±80.26, OI (mmHg, 1 mmHg = 0.133 kPa): 134.0 (77.5, 192.0) vs. 292.0 (187.0, 329.0), AST (U/L): 254.00 (67.80, 452.50) vs. 85.50 (38.38, 111.25), K + (mmol/L): 4.06 (3.65, 4.51) vs. 3.52 (3.26, 3.76), SF (μg/L): 6 290.0 (1 851.0, 13 904.8) vs. 1 777.1 (1 228.5, 3 486.3), LDH (μmol·s -1·L -1): 19.3 (11.9, 27.0) vs. 9.8 (6.9, 11.1), all P < 0.05]. In death group, duration of having a fever after admission was prolonged [days: 13.5 (9.0, 17.2) vs. 6.0 (2.5, 8.0), P < 0.05] and the incidence of cyanosis was higher (40.0% vs. 0%, P < 0.05). There was no significant difference in other indicators between the two groups. ② Multivariate Logistic regression analysis showed that low OI combined with high LDH were risk factors for 28-day mortality of adult patients with IAHS [odds ratio ( OR) was 0.967 and 1.007, respectively, both P < 0.05].③ It was shown by ROC curve analysis that WBC, NEU, AST, SF, LDH and OI had predictive value for 28-day prognosis of adult patients with IAHS (both P < 0.05), and the area under ROC curve (AUC) of OI and LDH was higher, that was both 0.847. When the best cut-off of OI was 145.5 mmHg, the sensitivity was 63.2%, and the specificity was 100%. When the best cut-off of LDH was 13.4 μmol·s -1·L -1, the sensitivity was 72.2%, and the specificity was 91.7%. Conclusion:OI < 145.5 mmHg, and LDH > 13.4 μmol·s -1·L -1 were significant predictors for poor 28-day prognosis of adult patients with IAHS.

Analysis of the clinical characteristics of severe tsutsugamushi disease in Yunnan Province from 2017 to 2018 / 中华危重病急救医学

To analyze the clinical characteristics of severe tsutsugamushi disease, and to improve the ability of clinicians to recognize severe cases. Methods The clinical data of patients with tsutsugamushi disease from January 1st, 2017 to December 31st, 2018 in hospitals of Yunnan Province were retrospectively collected by the Case Report Form (CRF). The age, gender, clinical symptoms at admission; white blood cell (WBC), eosinophil count (EO), red blood cell (RBC), platelet count (PLT), hemoglobin (Hb), hematocrit (HCT), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), serum creatinine (SCr), uric acid (UA) on the first day of admission; and clinical outcomes were recorded. The patients were divided into the non-critical group and the critical group according to the diagnostic criteria, the data of clinical manifestation, laboratory examination, imaging examination and prognosis were compared between the two groups. Multivariate Logistic regression analysis was performed on the variables with statistical significance. The receiver operating characteristic (ROC) curve of LDH and UA for differential diagnosis of severe tsutsugamushi disease were drawn. Results From January 1st, 2017 to December 31st, 2018, 408 patients with tsutsugamushi disease were enrolled in 37 hospitals in 15 prefectures and municipalities of Yunnan Province. 385 cases were clinically diagnosed and 23 cases were laboratory diagnosed. There were 265 cases in non-critical group and 143 cases in critical group. A total of 8 cases died and the remaining 400 cases were discharged from hospital. ① Compared with the non-critical group, age of the critical group was older, the incidence of dizziness, cough, expectoration, general soreness, dyspnea, palpitation, abdominal pain, diarrhea, bulbar conjunctival congestion, pleural effusion, peritoneal effusion, pericardial effusion, hepatomegaly, splenomegaly, and the levels of WBC, ALT, AST, LDH, TBil, BUN, SCr, UA were significantly increased, the incidence of lymph node enlargement and the levels of EO, PLT and ALB were significantly decreased, and there was no significant difference in other indicators between the two groups.② Multivariate Logistic regression analysis showed that age, dyspnea, palpitations, LDH, UA, ALB were risk factors for severe tsutsugamushi disease, βvalue was 0.040,-2.147,-1.414, 0.002, 0.005 and-0.132 respectively, and the odds ratio (OR) was 1.041, 0.117, 0.243, 1.002, 1.005 and 0.877 respectively (all P < 0.01). ③ROC curve analysis showed that UA and LDH had better accuracy in differential diagnosis of severe tsutsugamushi disease (both P < 0.01), and the area under ROC curve (AUC) was 0.693 [95% confidence interval (95%CI) = 0.633-0.754], 0.819 (95%CI = 0.776-0.862), respectively. When the cut-off of UA was 306.2 μmol/L, the sensitivity was 60.8%, and the specificity was 77.4%. When the cut-off of LDH was 485.5 U/L, the sensitivity was 74.8%, and the specificity was 74.7%. The diagnostic value of UA combined with LDH was higher, AUC was 0.832, the sensitivity was 69.9%, and the specificity was 85.3%. Conclusion Severe tsutsugamushi disease can be diagnosed at an early stage according to age, respiratory distress, palpitations, hypoalbuminemia, UA >306.2 μmol/L, and LDH > 485.5 U/L.

Feasibility of difference between hematocrit and albumin for identifying severity of scrub typhus disease / 中华危重病急救医学

Objective To explore the feasibility of difference between hematocrit and albumin (HCT-ALB) to evaluate the severity in patients with severe scrub typhus (Tsutsugamushi disease). Methods The clinical data of 408 patients with scrub typhus in 37 hospitals located in 15 prefectures of Yunnan Province from January 1st, 2017 to December 31st, 2018 were retrospectively collected. The patients were divided into the non-severe scrub typhus disease group (n = 265) and the severe scrub typhus disease group (n = 143) according to the diagnostic criteria. Volunteers attending Kunming City Medical Center in Yunnan Province for routine physical examination were enrolled as healthy control group (n = 230). HCT, ALB, lactate dehydrogenase (LDH), uric acid (UA), and acute physiology and chronic health evaluationsⅡ(APACHEⅡ) and sequential organ failure assessment (SOFA) within 24 hours after admission were collected. HCT-ALB difference was calculated. Pearson method was used to analyze the correlation between HCT-ALB difference and LDH, UA, APACHEⅡ and SOFA scores in patients with severe scrub typhus disease; the receiver operating characteristic (ROC) curve was used to analyze the value of HCT-ALB difference in the diagnosis of severe scrub typhus disease. Results ① There was no significant difference in gender composition between patients with non-severe scrub typhus disease group and severe scrub typhus disease group, but the age of the severe scrub typhus disease group was significantly higher than that of the non-severe scrub typhus disease group (years old: 53.57±15.23 vs. 35.03±23.47, P < 0.01). ② Compared with the healthy control group, the HCT, ALB of the non-severe scrub typhus disease group and severe scrub typhus disease group were significantly decreased [HCT: (36.54±6.82)％, (38.13±7.60)％vs. (46.20±4.42)％; ALB (g/L): 35.53±5.87, 26.90±6.10 vs. 47.75±4.28, all P < 0.01], and the HCT-ALB difference was significantly increased (5.28±3.90, 11.26±6.62 vs. 1.55±5.32, both P < 0.01). Compared with the non-severe scrub typhus disease group, the HCT of the severe scrub typhus disease group was significantly increased [(38.13±7.60)％vs. (36.54±6.82)％, P < 0.01], the ALB was significantly decreased (g/L: 26.90±6.10 vs. 35.53±5.87, P < 0.01), and the HCT-ALB difference was significantly increased (11.26±6.62 vs. 5.28±3.90, P < 0.01). ③ Pearson correlation analysis showed that HCT-ALB difference was positively correlated with LDH and UA in patients with severe scrub typhus disease (r values were 0.316 and 0.284, respectively, both P < 0.01), and negatively correlated with APACHEⅡ score and SOFA score (r values were -0.229 and -0.198, respectively, both P < 0.05). ④ ROC curve analysis showed that the area under the curve (AUC) of HCT-ALB difference in the diagnosis of severe scrub typhus disease was 0.786, standard error was 0.024, P = 0.000, and 95％ confidence interval (95％CI) was 0.739-0.832. When the best diagnostic value was 8.56, the sensitivity was 81.1％, the specificity was 60.8％, and the Youden index was 0.419. Conclusions HCT-ALB difference is an indicator to evaluate the severe scrub typhus disease. When HCT-ALB difference is above 8.56, it can be used as an indicator to identify severe scrub typhus disease.

Feasibility of difference between hematocrit and albumin for identifying severity of scrub typhus disease / 中华危重病急救医学

Objective@#To explore the feasibility of difference between hematocrit and albumin (HCT-ALB) to evaluate the severity in patients with severe scrub typhus (Tsutsugamushi disease).@*Methods@#The clinical data of 408 patients with scrub typhus in 37 hospitals located in 15 prefectures of Yunnan Province from January 1st, 2017 to December 31st, 2018 were retrospectively collected. The patients were divided into the non-severe scrub typhus disease group (n = 265) and the severe scrub typhus disease group (n = 143) according to the diagnostic criteria. Volunteers attending Kunming City Medical Center in Yunnan Province for routine physical examination were enrolled as healthy control group (n = 230). HCT, ALB, lactate dehydrogenase (LDH), uric acid (UA), and acute physiology and chronic health evaluationsⅡ(APACHEⅡ) and sequential organ failure assessment (SOFA) within 24 hours after admission were collected. HCT-ALB difference was calculated. Pearson method was used to analyze the correlation between HCT-ALB difference and LDH, UA, APACHEⅡ and SOFA scores in patients with severe scrub typhus disease; the receiver operating characteristic (ROC) curve was used to analyze the value of HCT-ALB difference in the diagnosis of severe scrub typhus disease.@*Results@#① There was no significant difference in gender composition between patients with non-severe scrub typhus disease group and severe scrub typhus disease group, but the age of the severe scrub typhus disease group was significantly higher than that of the non-severe scrub typhus disease group (years old: 53.57±15.23 vs. 35.03±23.47, P < 0.01). ② Compared with the healthy control group, the HCT, ALB of the non-severe scrub typhus disease group and severe scrub typhus disease group were significantly decreased [HCT: (36.54±6.82)%, (38.13±7.60)% vs. (46.20±4.42)%; ALB (g/L): 35.53±5.87, 26.90±6.10 vs. 47.75±4.28, all P < 0.01], and the HCT-ALB difference was significantly increased (5.28±3.90, 11.26±6.62 vs. 1.55±5.32, both P < 0.01). Compared with the non-severe scrub typhus disease group, the HCT of the severe scrub typhus disease group was significantly increased [(38.13±7.60)% vs. (36.54±6.82)%, P < 0.01], the ALB was significantly decreased (g/L: 26.90±6.10 vs. 35.53±5.87, P < 0.01), and the HCT-ALB difference was significantly increased (11.26±6.62 vs. 5.28±3.90, P < 0.01). ③ Pearson correlation analysis showed that HCT-ALB difference was positively correlated with LDH and UA in patients with severe scrub typhus disease (r values were 0.316 and 0.284, respectively, both P < 0.01), and negatively correlated with APACHEⅡ score and SOFA score (r values were -0.229 and -0.198, respectively, both P < 0.05). ④ ROC curve analysis showed that the area under the curve (AUC) of HCT-ALB difference in the diagnosis of severe scrub typhus disease was 0.786, standard error was 0.024, P = 0.000, and 95% confidence interval (95%CI) was 0.739-0.832. When the best diagnostic value was 8.56, the sensitivity was 81.1%, the specificity was 60.8%, and the Youden index was 0.419.@*Conclusions@#HCT-ALB difference is an indicator to evaluate the severe scrub typhus disease. When HCT-ALB difference is above 8.56, it can be used as an indicator to identify severe scrub typhus disease.

Role of pancreatic hilar vascular occlusion in sophisticated pancreaticoduodenectomy / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the value of a simple occlusive technique of the triple vessels, ie, portal vein, superior mesenteric vessels and splenic vein, in complicated pancreaticoduodenectomy.</p><p><b>METHODS</b>The technique was fulfilled with a No.8 urethral catheter to encycle the portal vein, superior mesenteric vessels and its near tissue plus pancreatic tail and splenic vein than the neck of pancreas was transected and well exposure superior mesenteric vein and complete transaction of uncinate. From November 2005 to November 2006 the technique was applied to 12 cases of pancreatic malignancy which presented very infiltrated and adhesive to the hilar vascular structure.</p><p><b>RESULTS</b>The 12 cases were accomplished according with this technique. The operating time was (292.4 +/- 36.3) min (270 - 390 min) and the intraoperative blood loss was (833.3 +/- 618.4) ml (300 - 2500 ml). The postoperative complication included one case of lymphatic leakage, two cases of pneumonia, one case of abdominal infection and two cases of wound infection. There was no perioperative mortality. The postoperative hospital stay was 17 d (11 - 29 d).</p><p><b>CONCLUSIONS</b>Use this triple vessels occlusive technique can improve the safety and feasibility in complicated cases of pancreaticoduodenectomy.</p>

The strategy of isolated complete resection of the caudate lobe of the liver through the anterior liver-splitting approach: a report of 19 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the strategy of isolated complete resection of the caudate lobe of the liver through the anterior liver-splitting approach.</p><p><b>METHODS</b>From January 1995 to June 2006, isolated complete caudate resection of the caudate lobe of the liver through the anterior liver-splitting approach in which accessed the caudate lobe by separation the liver parenchyma along the interlobar plane, was performed on 19 patients with tumors originated in caudate lobe. They were included hepatocellular carcinoma in 13 cases, cholangiocarcinoma in 4 cases and hemangioma in 2 cases, the tumor size range from 4 - 12 cm. The approach to hepatic resection involved routine use of Peng's multifunctional operative dissector, inflow and outflow of hepatic vascular control before hepatic parenchyma transection, low central venous pressure and selective use of liver hanging maneuver, as well as retrograde caudate lobectomy.</p><p><b>RESULTS</b>The operations were successful in 19 patients. Operating time averaged at (296 +/- 55) min. The average amount of blood loss were 1200 ml (ranged from 500 - 3000 ml). Postoperative complications included ascites in 2 cases, pleural effusion in 5 cases and bile leakage in 2 cases. They were cured by drainage. No mortality occurred in the perioperative period.</p><p><b>CONCLUSIONS</b>The application of anterior approach for isolated caudate lobectomy can converse certain kind of caudate lobe tumor from non-resectable to respectable resulting in widening the indication. The intraoperative routine use of Peng's multifunctional operative dissector, application of inflow and outflow of hepatic vascular control, low central venous pressure and selective use of liver hanging maneuver, as well as retrograde caudate lobectomy make the anterior liver-splitting approach for isolated complete caudate lobectomy safer and easier.</p>

Surgical treatment of hepatocellular carcinoma with tumor thrombus in inferior vena cava / 中华外科杂志

<p><b>OBJECTIVE</b>To review the experience for the management of hepatocellular carcinoma with tumor thrombus in inferior vena cava.</p><p><b>METHODS</b>From July 2003 to May 2005, hepatectomy combined with thrombectomy were performed on 7 cases of hepatocellular carcinoma with tumor thrombus in inferior vena cava. In order to remove the tumor thrombus in inferior vena cava, total hepatic vascular exclusion were adopted on all cases to control the blood flow of IVC. According to the position of extension of tumor thrombus, 5 different procedures were adopted in the cases to control the suprahepatic IVC and extract the tumor thrombus out of IVC and atrium. Procedure 1: Median sternotomy, extracorporeal bypass, cardiac arrest, incision on right atrium and IVC were performed on 1 case for thrombectomy. Procedure 2: Median sternotomy, extracorporeal bypass without cardiac arrest, incision on IVC and (or without) incision on right atrium were performed on 2 cases for thrombectomy. Procedure 3: Abdominal approach to control intrapericardial IVC through an incision on diaphragm was performed on 1 case for thrombectomy. Procedure 4: Abdominal approach to control suprahepatic IVC above diaphragm through a small incision made on vena cava foramen for thrombectomy was performed on 1 case. Procedure 5: Abdominal approaches to control suprahepatic IVC below diaphragm for thrombectomy were performed on 2 cases.</p><p><b>RESULTS</b>All operations were successfully performed. The postoperative complications included pleural effusion in 1 case, subphrenic fluid collection in 1 case and wound infection in 1 case. The average survival time of 7 cases was 9.8 month. The longest survival time was 26 months.</p><p><b>CONCLUSION</b>Hepatectomy and thrombectomy can be safely performed on the case of HCC combined with tumor thrombus in IVC. Surgical treatment can relieve the patient from the risk of sudden death caused by heart failure and pulmonary.</p>

The study on immunomodulation of donor mesenchymal stem cells on discordant liver xenotransplantation / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the influence of guinea pig mesenchymal stem cells (MSCs) culture in vitro on the immunological status in heterogeneous recipient, and to evaluate the immunomodulation of MSCs to the immune rejection of liver xenotransplantation.</p><p><b>METHODS</b>The mononuclear cell fraction obtained by centrifugation over Percoll was cultured in vitro. Cell surface epitopes were analyzed by flow cytometry technique, and MSCs were incubated at the addition of adipocyte induction media, and stained in Oil Red O. The immunoglobulin and complement in rat recipient serum were assayed after infusion of donor MSCs. Thirty guinea pigs and thirty Wistar rats were randomly divided into three groups. All rat recipients undertook cyclophosphamide (CTX) infusion. Group A was MSCs infusion group, group B was saline infusion group and group C was dexamethasone (DXM) infusion group. Orthotopic guinea pig to rat liver transplantation model was established. The survival time and the immunopathology of graft were observed.</p><p><b>RESULTS</b>According to flow cytometry assay, MSCs were positive for CD44 and CD29, while negative for CD34 and CD45. Lipid droplets were found in the MSCs cytoplasm after being incubated in adipogenic inducation media. The concentrations of IgG, IgM, C3 at all time point after MSCs infusion were significantly decreased than before (P < 0.05), while the concentrations of IgA and C4 did not changed. The survival time of group A (431 +/- 27 min) was obviously longer than group B (148 +/- 16 min) and group C (141 +/- 22 min) (P < 0.01). The intense hyperacute rejection rapidly occurred of group B and C after blood re-perfusion. The severe immunopathological injury could be observed at the grafts of group B and C. However, the hyperacute rejection of group A occurred slightly.</p><p><b>CONCLUSIONS</b>MSCs can be identified by virtue of cell morphology, membrane phenotype and differential potential. MSC may play a role in the immunosuppression in hyperacute rejection in the liver xenotransplantation.</p>

Surgical treatment of hepatocellular carcinoma originating from caudate lobe / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the significance of surgical treatment of HCC originating from caudate lobe.</p><p><b>METHODS</b>From 1995 to 2003, caudate lobectomy, including 19 cases of isolated lobectomy and 20 cases of combined lobectomy, were performed in 39 patients with HCC originating from caudate lobe, and the factors that might influence postoperative liver function were compared between the two groups.</p><p><b>RESULTS</b>All tumors were resected successfully. One patient died of postoperative renal failure. Hydrothorax occurred in 3 patients, ascites in 4 patients, and bile leakage in 1 patient. The survival rates of 1, 3, 5 year were 53%, 50%, 39% respectively.</p><p><b>CONCLUSIONS</b>Caudate lobectomy is a effective method for HCC originating from caudate lobe.</p>

Retrograde caudate lobectomy in 7 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the clinical value and significance of retrograde caudate lobectomy.</p><p><b>METHODS</b>From December 2003 to January 2005, 7 patients underwent retrograde caudate lobectomy in which division and ligation of short hepatic veins were carried out at the final stage of the procedure in stead of at the initial stage.</p><p><b>RESULTS</b>The procedures were carried out smoothly with no operative death in all the 7 cases including isolated complete caudate lobectomy in 4 cases, isolated partial caudate lobectomy in 1 case, combined right half liver resection in 2 case. The average operation time, blood loss and length of stay after operation was (273 +/- 44) min, (1114 +/- 241) ml (800-1500 ml) and 16 days respectively. Complications including pleural effusion and ascites in 1 case respectively were fully recovered. During the follow-up, 1 patient died at 6 months for tumor recurrence in lung and the remaining 6 patients are alive at the follow-up of 5 to 16 months.</p><p><b>CONCLUSIONS</b>Retrograde caudate lobectomy is a new procedure suitable for those caudate neoplasms which are adhering to or infiltrating to IVC or too big to move side by side. The application of this technique can converse certain kind of caudate lobe tumor from non-resectable to resectable resulting in widening the indication.</p>