Elemene Antitumor Drugs Development Based on "Molecular Compatibility Theory" and Clinical Application: A Retrospective and Prospective Outlook / 中国结合医学杂志

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".

Elemene Enhances Anti-glioma Effect of Cabazitaxel and Its Dual-targeted Cationic Liposome Preparation Optimization and in Vitro Pharmacodynamic Evaluation / 中国实验方剂学杂志

ObjectiveTo investigate whether elemene（ELE） enhances the anti-glioma efficacy of cabazitaxel（CTX）， and prepare a double-targeted cationic liposome（LIP） co-loaded with ELE/CTX for the treatment of glioma， and to achieve the effect of increasing the efficacy and reducing the adverse reactions. Pharmacodynamic tests in vitro were performed to explore the advantages and mechanism of its preparation. MethodELE/CTX@LIP was prepared by high speed shear combined with probe ultrasound， the particle size and potential were characterized by nano-particle size potentiometer， and high performance liquid chromatography（HPLC） was used to determine the encapsulation efficiency and drug loading capacity of CTX/ELE. The cytotoxicity of ELE/CTX in vitro was detected by cell proliferation and activity assay（CCK8）. JMP Pro 16 software was used to optimize the process parameters of ELE/CTX@LIP based on encapsulation efficiency. The optimal cationic material type， content and ratio were screened by in vitro cytotoxicity and in vitro cell uptake， on this basis， the dual-targeted cationic liposome T7/arginine glycine aspartate tripeptide sequence（T7/cRGD）-ELE/CTX@CLIP was prepared， the stability of morphology and particle size were characterized， and the effect of T7/cRGD-ELE/CTX@CLIP on the apoptosis inducing ability and cell cycle regulation ability of glioma cells was analyzed by cell cycle and apoptosis. ResultELE/CTX showed stronger anti-glioma activity on C6 and RG2 cells. The results of in vitro cytotoxicity and in vitro cell uptake showed that the amount of cationic material was 0.10% of the total content. The optimum ratio of T7， cRGD and phospholipids was 1∶1∶50. T7/cRGD-ELE/CTX@CLIP［1，2-dilinoleyloxy-3-dimethylaminopropane（Dlin-MC3-DMA）］ and T7/cRGD-ELE/CTX@CLIP［1，2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol 2000（DMG-PEG2000）］ showed multi-level spherical nanostructures with particle sizes of 146.0， 111.3 nm， respectively， and were stable in serum. In vitro cytotoxicity results showed that T7/cRGD-ELE/CTX@CLIP had higher cytotoxicity to glioma cells than single-targeted liposomes or dual-targeted non-cationic liposomes. T7/crGD-ELE/CTX@CLIP affected the apoptosis and cycle of glioma cells， the results showed that ELE/CTX combined with liposomes could more effectively activate the apoptosis channel and inhibit the proliferation of glioma cells， and the use of T7/cRGD short peptide and cation modification enhanced the ability of apoptosis induction. ELE/CTX could effectively block glioma cell cycle at G2/M phase， and the effect was enhanced after T7/cRGD targeted modification. ConclusionELE can enhance the anti-glioma effect of CTX. The preparation parameters of ELE/CTX@LIP are stable and feasible. Combined with the in vitro efficacy test， the anti-glioma mechanism of T7/cRGD-ELE/CTX@CLIP is preliminarily revealed.

Whole-process individualized pharmaceutical care for a case of melioidosis sepsis / 中国药房

OBJECTIVE To provide reference for the adjustment of antibiotic treatment regimens， identification of adverse reactions， and individualized pharmaceutical care for melioidosis sepsis （MS）. METHODS Clinical pharmacists participated in the intensive and eradicating therapeutic processes for an MS patient by using blood concentration and gene detection. Based on the literature， antibiotic treatment regimens of MS were adjusted by determining the blood concentrations of β-lactam and trimethoprim/ sulfamethoxazole （TMP/SMZ） and calculating PK/PD parameters. The causes of adverse drug reactions were analyzed and addressed by detecting drug-related gene polymorphisms through high-throughput sequencing. RESULTS Clinical pharmacists used blood concentration and genetic testing methods to propose adjustments to imipenem-cilastatin sodium dosage and analyze the causes of various adverse drug reactions. PK/PD targets were calculated by measuring the blood concentrations of β-lactam and TMP/SMZ. Clinical pharmacists explained to clinical doctors the compliance status of patients with melioidosis in sepsis and non- sepsis stages through reviewing guidelines and literature； the results of blood concentration and genetic test were used to analyze the correlation of neurotoxicity of MS patients with B14） IMP cmin， and it was found that nephrotoxicity was not related to the cmax of TMP/SMZ， but to the patient’s water intake. After whole-process antibiotic treatment， the patient’s condition improved and was discharged， and the adverse reactions were effectively treated. CONCLUSIONS Clinical pharmacists use blood concentration and genetic tests to assist clinicians in formulating MS treatment regimens， and provide whole-course pharmaceutical care for a MS patient. This method has improved the safety and effectiveness of clinical drug therapy.

Postoperative awake prone position in geriatric patients with hip fractures: a protocol for a randomized controlled trial on the efficacy of postoperative prone position in reducing pulmonary complications and improving oxygenation.

INTRODUCTION: Postoperative pulmonary complications (PPCs) are prevalent in geriatric patients with hip fractures. Low oxygen level is one of the most important risk factors for PPCs. Prone position has been proven efficacy in improving oxygenation and delaying the progress of pulmonary diseases, especially in patients with acute respiratory distress syndrome induced by multiple etiologies. The application of awake prone position (APP) has also attracted widespread attention in recent years. A randomized controlled trial (RCT) will be carried out to measure the effect of postoperative APP in a population of geriatric patients undergoing hip fracture surgery. METHODS: This is an RCT. Patients older than 65 years old admitted through the emergency department and diagnosed with an intertrochanteric or femoral neck fracture will be eligible for enrollment and assigned randomly to the control group with routine postoperative management of orthopedics or APP group with an additional prone position for the first three consecutive postoperative days (PODs). Patients receiving conservative treatment will not be eligible for enrollment. We will record the difference in the patient's room-air-breathing arterial partial pressure of oxygen (PaO2) values between the 4th POD (POD 4) and emergency visits, the morbidity of PPCs and other postoperative complications, and length of stay. The incidence of PPCs, readmission rates, and mortality rates will be followed up for 90 PODs. DISCUSSION: We describe the protocol for a single-center RCT that will evaluate the efficacy of postoperative APP treatment in reducing pulmonary complications and improving oxygenation in geriatric patients with hip fractures. ETHICS AND DISSEMINATION: This protocol was approved by the independent ethics committee (IEC) for Clinical Research of Zhongda Hospital, Affiliated to Southeast University, and is registered on the Chinese Clinical Trial Registry. The findings of the trial will be disseminated through peer-reviewed journals. ETHICS APPROVAL NUMBER: 2021ZDSYLL203-P01 TRIAL REGISTRATION: ChiCTR ChiCTR2100049311 . Registered on 29 July 2021. TRIAL STATUS: Recruiting. Recruitment is expected to be completed in December 2024.

Research progress in chemical constituents, pharmacological effects, and clinical application of Curcuma wenyujin and prediction of its quality markers / 中国中药杂志

Curcuma wenyujin, as one of the eight Daodi-herbs in Zhejiang province, is widely used. It has the effects of eliminating stasis and dissipating mass, moving Qi and activating blood, and clearing heart and relieving depression. Modern studies have shown that it has anti-tumor, anti-inflammatory, anti-oxidation, anti-thrombus and liver-protecting effects and mainly contains sesquiterpenoids, monoterpenoids, diterpenoids, and curcumins. This paper reviews the research progress in the chemical constituents and pharmacological effects of C. wenyujin in the last decade, discusses the modern clinical applications combined with the traditional efficacy, and predicts its quality markers(Q-markers) from plant consanguinity, medicinal properties, efficacy, processing and measurability of chemical components based on the theory of Q-markers, so as to provide a reference for the establishment of a scientific quality evaluation system and the research and application of this herb in the future.

Discovery and bioassay of disubstituted β-elemene-NO donor conjugates: synergistic enhancement in the treatment of leukemia / 中国天然药物

Natural products are essential sources of antitumor drugs. One such molecule, β-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β-elemene derivatives were designed, with β-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.

Comparative efficacy of awake prone positioning combined with standardized nursing care and standardized nursing care in the prevention of early postoperative pulmonary complications in elderly patients with hip fracture / 中华创伤杂志

Objective:To compare the effectiveness of awake prone positioning (APP) care combined with standardized nursing and standardized nursing care in the prevention of early postoperative pulmonary complications (PPCs) in elderly patients with hip fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 84 elderly patients with hip fracture Admitted to Zhongda Hospital Affiliated to Southeast University from February 2021 to August 2021. There were 31 males and 53 females, aged 67-96 years [(82.3±6.3)years]. Fracture types were femoral neck fracture ( n=45) and intertrochanteric fracture ( n=39). Surgical procedures included closed reduction internal fixation ( n=39), hip hemiarthroplasty ( n=35), and total hip arthroplasty ( n=10). Among them, 42 patients received standardized nursing care and APP intervention (APP combined with standardized nursing care group), while the remaining 42 patients received standardized nursing care only (standardized nursing care group). The incidence rate of PPCs (including pneumonia, respiratory failure, pleural effusion, atelectasis and pulmonary edema) within 30 postoperative days, arterial oxygen pressure (PaO 2), arterial carbon dioxide pressure (PaCO 2), arterial oxygen saturation (SaO 2) on the 4th postoperative day, difference in PaO 2 between the 4th postoperative day and emergency visit, clinical pulmonary infection score (CPIS) on the 4th postoperative day, and number of adverse events related to APP were compared between the two groups. Results:All the patients were followed up for 30-90 days [(86.1±16.5)days]. The incidence rates of PPCs and type 1 postoperative respiratory failure in the APP combined with standardized nursing care group were 16.7% (7/42) and 4.8% (2/42), and were 35.7% (15/42) and 21.4% (9/42) in the standardized nursing care group (all P<0.05). The PaO 2 and SaO 2 on the 4th postoperative day, and difference in PaO 2 between the 4th postoperative day and emergency visit were (82.0±8.8)mmHg, 0.96±0.01, and 3.2 (-1.9, 8.0)mmHg in the APP combined with standardized nursing care group, and were (74.3±12.1)mmHg, 0.94±0.03, and -7.6 (-17.2, 1.1)mmHg in the standardized nursing care group (all P<0.01). The CPIS on the 4th postoperative day was 2.0 (1.0, 3.0)points in the APP combined with standardized nursing care group and 4.0 (1.0, 7.0)points in the standardized nursing care group ( P<0.05). No statistically significant differences were observed in the incidence of pneumonia, type I respiratory failure, pleural effusion, atelectasis and pulmonary edema within 30 postoperative days, as well as PaCO 2 on the 4th postoperative day between the two groups (all P>0.05). None of the patients experienced adverse events related to APP. Conclusion:For elderly patients with hip fracture, compared with standardized nursing care, application of APP combined with standardized nursing care can significantly decrease the incidence rate of early PPCs, especially type I respiratory failure, and improve postoperative oxygenation.

Tumor cell membrane-coated continuous electrochemical sensor for GLUT1 inhibitor screening / 药物分析学报

Glucose transporter 1(GLUT1)overexpression in tumor cells is a potential target for drug therapy,but few studies have reported screening GLUT1 inhibitors from natural or synthetic compounds.With cur-rent analysis techniques,it is difficult to accurately monitor the GLUT1 inhibitory effect of drug molecules in real-time.We developed a cell membrane-based glucose sensor(CMGS)that integrated a hydrogel electrode with tumor cell membranes to monitor GLUT1 transmembrane transport and screen for GLUT1 inhibitors in traditional Chinese medicines(TCMs).CMGS is compatible with cell membranes of various origins,including different types of tumors and cell lines with GLUT1 expression knocked down by small interfering RNA or small molecules.Based on CMGS continuous monitoring technique,we inves-tigated the glucose transport kinetics of cell membranes with varying levels of GLUT1 expression.We used CMGS to determine the GLUT1-inhibitory effects of drug monomers with similar structures from Scutellaria baicalensis and catechins families.Results were consistent with those of the cellular glucose uptake test and molecular-docking simulation.CMGS could accurately screen drug molecules in TCMs that inhibit GLUT1,providing a new strategy for studying transmembrane protein-receptor interactions.

Influence of NDR1 on prognosis of patients with hepatocellular carcinoma and effect on proliferation and migration of hepatocellular carcinoma cells / 安徽医科大学学报

Objective@#To analyze the expression and clinical prognostic significance of nuclear Dbf2-related kinase 1 ( NDR1 ) in hepatocellular carcinoma ，and to investigate the biological function and regulatory mechanism of NDR1 in hepatocellular carcinoma cells．@*Methods@#ENCORI database was used to analyze the correlation of NDR1 and c-Myc．Cycloheximide ( CHX) experiment analyzed the relationship between NDR1 and c-Myc protein stability．The expression levels of NDR1 in liver cancer tissues and normal tissues and its relationship with the survival rate of liver cancer patients were analyzed using the ENCORI database．MYC-NDR1 eukaryotic expression vector was constructed，transfected with hepatocellular carcinoma HepG2 cells，and its expression was verified by protein immuno blotting (Western blot) ; cell proliferation and migration ability were detected by CCK-8 assay，cell clone formation assay and scratch assay，respectively．The correlation between NDR1 and c-Myc expression was analyzed using the ENCORI database，and the relationship between NDR1 and c-Myc protein was investigated using a protein synthesis inhibitor CHX dosing assay. @*Results@#The results of the ENCORI database showed that the expression of NDR1 in liver cancer tissues was higher than that in normal tissues and the overall survival rate of patients with high NDR1 expression was lower than that of patients with low NDR1 expression，and the difference was statistically significant (P＜0. 001) ．The results of the CCK-8 assay showed that the MYC-NDR1 group grew faster than the empty vector group (P＜0. 001) ．The clone formation assay showed that the number of clones in the MYC-NDR1 group was higher than that in the empty vector group (P＜0. 001) ．The cell scratch assay showed that the mean migration distance in the MYC-NDR1 group was greater than that in the empty vector group (P＜0. 001) ．ENCORI database analysis showed that NDR1 correlated with c-Myc expression (R = 0. 184，P＜0. 001) ; CHX dosing assay showed that the reduction of c-Myc protein in the MYC-NDR1 group was lower than that in the empty vector group during the same time．@*Conclusion@#NDR1 is highly expressed in hepatocellular carcinoma tissues，closely correlated with poor prognosis of hepatocellular carcinoma patients ，and positively correlated with the expression of c-Myc gene. The study successfully constructes MYC-NDR1 eukaryotic expression vector ，and the expression product MYC- NDR1 can increase the stability of c-Myc protein and promote the proliferation and migration of human hepatocellu- lar carcinoma cells.

Advances in antiviral research of adaptor-associated protein kinase 1 (AAK1) inhibitors / 药学学报

As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.

Risk factors for one-year mortality in elderly patients with femoral intertrochanteric fracture following multidisciplinary treatment by intramedullary nailing / 中华创伤骨科杂志

Objective:To analyze the risk factors for postoperative one-year mortality in elderly patients with femoral intertrochanteric fracture following multidisciplinary treatment (MDT) by intramedullary nailing.Methods:The clinical data were retrospectively analyzed of the 158 elderly patients with femoral intertrochanteric fracture who had undergone MDT by proximal femoral intramedullary nailing between January 2018 and August 2020 at Department of Orthopedics, Trauma Center, Zhongda Hospital Affiliated to Southeast University. There were 41 males and 117 females with an average age of 82.5 years (from 65 to 95 years). By the modified Evans classification, there were 15 cases of type Ⅰ, 16 cases of type Ⅱ, 35 cases of type Ⅲ, 81 cases of type Ⅳ, and 11 cases of type Ⅴ. The one-year mortality was documented in the patients after surgery. To screen for risk factors, univariate analysis was conducted of gender, age, body mass index (BMI), modified Evans classification of fractures, time from injury to operation, American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI) and comorbidities, as well as preoperative hemoglobin (Hb), serum albumin (ALB) and total lymphocyte count (TLC). The factors with P<0.05 were included in the multivariate logistic regression model analysis to determine the risk factors. Results:A total of 13 patients died within one year after surgery, yielding a mortality of 8.2% (13/158). Univariate analysis showed significant differences in age, body mass index, modified Evans classification of fractures, CCI and Hb between the surviving and dead patients ( P<0.05). Multivariate logistic regression analysis showed that age >85 years ( OR=0.122, 95% CI: 0.018 to 0.834, P=0.032), BMI>23.9 kg/m 2 ( OR=0.083, 95% CI: 0.013 to 0.510, P=0.007), CCI≥3 points ( OR=0.051, 95% CI: 0.090 to 0.275, P=0.001) and preoperative Hb<90 g/L ( OR=4.733, 95% CI: 1.036 to 21.624, P=0.045) were the independent risk factors for postoperative one-year mortality in the elderly patients with intertrochanteric fracture following MDT by proximal femoral intramedullary nailing. Conclusions:After MDT by proximal femoral intramedullary nailing of femoral intertrochanteric fractures, the geriatric patients with an age >85 years, BMI>23.9 kg/m 2, CCI≥3 points and Hb<90 g/L are likely to die. Therefore, special care should be taken for them.

Research progress of ATR kinase-targeted inhibitors in the cancer therapy / 药学学报

Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.

A NIR fluorescent probe for Vanin-1 and its applications in imaging, kidney injury diagnosis, and the development of inhibitor

Vanin-1 is an amidohydrolase that catalyses the conversion of pantetheine into the amino-thiol cysteamine and pantothenic acid (coenzyme A precursor), which plays a vital role in multiple physiological and pathological processes. In this study, an enzyme-activated near-infrared (NIR) fluorescent probe (DDAV) has been constructed for sensitively detecting Vanin-1 activity in complicated biosamples on the basis of its catalytic characteristics. DDAV exhibited a high selectivity and sensitivity toward Vanin-1 and was successfully applied to the early diagnosis of kidney injury in cisplatin-induced kidney injury model. In addition, DDAV could serve as a visual tool for in situ imaging endogenous Vanin-1 in vivo. More importantly, Enterococcus faecalis 20247 which possessed high expression of Vanin-1 was screened out from intestinal bacteria using DDAV, provided useful guidance for the rational use of NSAIDs in clinic. Finally, oleuropein as a potent natural inhibitor for Vanin-1 was discovered from herbal medicines library using a high-throughput screening method using DDAV, which held great promise for clinical therapy of inflammatory bowel disease.

Risk factors of preoperative hypoxemia in geriatric patients with hip fracture / 中华创伤杂志

Objective:To investigate the risk factors for preoperative hypoxemia in geriatric patients with hip fracture.Methods:A case-control study was used to analyze the clinical data of 99 geriatric patients with hip fracture admitted to Zhongda Hospital affiliated to Southeast University between November 2020 and August 2021. There were 29 males and 70 females, aged 67-96 years [(82.6±6.2)years]. The patients were divided into hypoxemia group ( n=51) and non-hypoxemia group ( n=48) using partial arterial partial pressure of oxygen (PaO 2)<80 mmHg while breathing room air at emergency as the reference standard. The two groups were compared in terms of sex, age, fracture types, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, pulmonary diseases diagnosed by preoperative chest CT [atelectasis, pleural effusion, chronic obstructive pulmonary disease (COPD)], time from injury to visit, New York Heart Association (NYHA) classification, Barthel index, KATZ index, modified Medicine Research Council (mMRC) dyspnea scale, numeric rating scale (NRS), smoking, drinking, comorbidities (hypertension, diabetes mellitus, Parkinson′s disease, Alzheimer′s disease, cerebral infarction, coronary atherosclerotic heart disease), body temperature, blood routine test at first examination (erythrocyte count, leukocyte count, C-reactive protein, hemoglobin), biochemistry (serum albumin, blood glucose, blood creatinine, blood urea nitrogen), electrolyte (serum potassium, serum sodium), and other related examinations [D-dimer, brain natriuretic peptide (BNP), lactic acid]. Univariate analysis was performed to the correlation of those indicators with preoperative hypoxemia. Multivariate Logistic regression analysis was used to identify the independent risk factors for preoperative hypoxemia in geriatric patients with hip fracture. Results:Differences in sex, age, fracture types, BMI, pulmonary diseases diagnosed by preoperative chest CT, time from injury to visit, Barthel index, KATZ index, NRS, smoking, drinking, comorbidities, body temperature, first laboratory results of erythrocyte count, biochemistry, electrolyte and other related examinations were not statistically significant between the two groups (all P>0.05). The two groups showed statistical differences in ASA classification, NYHA classification, mMRC dyspnea scale, leukocyte count at first examination, C-reaction protein and hemoglobin (all P<0.05). Univariate analysis indicated that ASA classification, NYHA classification, mMRC dyspnea scale, leukocyte count at first examination and C-reaction protein were correlated with the occurrence of preoperative hypoxemia in geriatric patients with hip fracture (all P<0.05). Multivariate Logistic regressions analysis indicated that higher mMRC dyspnea scale ( OR=2.30, 95% CI 1.10-4.81, P<0.05), higher leukocyte count at first examination ( OR=1.24, 95% CI 1.05-1.45, P<0.05), higher level of C-reaction protein ( OR=1.02, 95% CI 1.01-1.03, P<0.05) and higher level of hemoglobin ( OR=1.04, 95% CI 1.01-1.07, P<0.05) were significantly correlated with the occurrence of preoperative hypoxemia in geriatric patients with hip fracture. Conclusion:Higher mMRC dyspnea scale, higher leukocyte count, higher level of C-reaction protein and higher level of hemoglobin are independent risk factors for preoperative hypoxemia in geriatric patients with hip fracture.

Research on Biosynthesis of Anticancer Drug Elemene and Key Enzyme Germacrane A Synthase / 中国生物化学与分子生物学报

Elemene is one of the anti-tumor drugs with independent intellectual property rights in China. It has the advantages of strong anti-tumor activity, wide range of action, mild side effects, and resistance to drug resistance, so it is widely used in the clinical treatment of various malignant tumors. The production of elemene mainly relies on the separation and extraction of the medicinal plant Curcuma wenyujin Y. H. Chen & C. Ling. However, the low content of elemene in the natural materials, complex extracting-process, low product-yield, and high cost, that seriously hinder the large-scale production and the application of elemene. With the development of synthetic biology, constructing cell factories to biosynthesize natural medicines has become a research hotspot, which also provides a new approach for the production of elemene. In recent years, the research on the biosynthesis of elemene has continued to deepen. Researchers have tried to clarify the biosynthesis pathway and key enzymes of elemene by means of metabolic engineering, combinatorial biology, genetic engineering. Some key enzyme genes in the biosynthetic pathway of elemene have been successfully cloned, and the heterologous biosynthesis of elemene has been preliminarily realized. This paper summarizes the elemene biosynthesis pathway and the optimization of engineered bacteria with a review of synthetic biology research thinking, and focuses on the key enzyme gemacrane A synthase (GAS). The optimization strategy of elemene biosynthesis is described, including the overexpression of key rate-limiting enzyme genes, the knockout of shunt genes, the enzymes engineering strategy of fusion expression, and in vitro evolution of key enzyme germacrane A synthetase. The problems and challenges faced in improving the yield of elemene in heterologous biosynthesis were also analyzed. The review will provide a reference for the efficient biosynthesis of elemene.

Black liquor increases methane production from excess pulp and paper industry sludge.

The aim of the study was to use black liquor produced during the soda pulping process in a pulp and paper mill to increase methane production during pulp and paper industry sludge treatment and decrease the treatment cost. The effects of black liquor on sludge solubilization and methane production were assessed and the economic feasibility of the process was evaluated. Black liquor and NaOH were found to be equivalent in the thermochemical pretreatment process to solubilize sludge and disintegrate flocs. However, adding black liquor increased the background chemical oxygen demand and volatile fatty acid concentration and increased the amount of methane produced by approximately 7-30%. A start-up delay was emphasized by first-order kinetics model due to black liquor addition while methane production remained stable. Economic assessments of five scenarios were performed. It was found to be economically feasible to use black liquor to replace NaOH for the thermal pretreatment process. The surplus methane generated suggested that co-digestion of sludge and black liquor allows surplus bioenergy to be produced during the thermochemical pretreatment anaerobic digestion process.

Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

Study on the application of oral digital design in aesthetic restoration of anterior teeth of cleft lip/palate patients / 华西口腔医学杂志

OBJECTIVES@#A study was conducted to investigate the clinical effects of oral digital design on the aesthetic restoration of anterior teeth of cleft lip/palate patients.@*METHODS@#Nine adult cleft lip/palate patients who need aesthetic restoration of anterior teeth were recruited. Digital information of patients' dental arches, the surrounding soft tissue and face were captured by digital camera and scanner. The aesthetic analysis and design were conducted using keynote and 3shape software and were demonstrated to the patients. The optimized treatment plan was ensured by communicating with the patients. Digital wax-up models were exported and printed into resin diagnostic models, which were then utilized in the treatment process to guide the doctors and the technicians in tooth preparation and in making the final restorations, respectively. The adhesive procedure was completed after satisfactory try-in. Aesthetics assessment was conducted in accordance with the anterior esthetic evaluation form. The scores of patient's satisfaction were recorded on a questionnaire containing six items of aesthetic index and doctor-patient communication. Patients were interviewed and examined after 1, 3, 6, and 12 months, respectively, and the clinical effects of restorations were evaluated.@*RESULTS@#All nine patients had satisfactory clinical results. The aesthetic defects of the patients were effectively addressed. All treatments met the requirements of the preoperative digital designs. The patients' scores were all above 90 on the satisfaction scale. At 12 months after the operation, the clinical effects of restorations of all cases achieved A class in each evaluation indicator.@*CONCLUSIONS@#For cleft lip/palate patients with esthetic defect in the anterior teeth, the digital design plays an important role in optimizing the treatment plan and guides the whole treatment process. This design can help clinicians achieve predictable satisfactory aesthetic results.

Clinical features, diagnosis, and treatment of Chinese children with Shwachman-Diamond syndrome / 中国当代儿科杂志

In order to clearly define the features of Shwachman-Diamond syndrome (SDS) in Chinese children, this article analyzes and summarizes the epidemiology, clinical features, and key points in the diagnosis and treatment of SDS in Chinese children with review of the clinical data of 27 children with SDS from related articles published previously. A comparative analysis was made between the Chinese and international data related to childhood SDS. The results showed a male/female ratio of about 2:1 in the Chinese children with SDS, with an age of onset of <1 month to 5 years (median 1 month) and an age of 3 months to 12 years (median 12 months) at the time of confirmed diagnosis. Reductions in peripheral blood cells due to myelopoiesis inhibition were observed in all 27 children with SDS, among whom 93% had neutropenia. Chronic diarrhea (85%), liver damage (78%), and short stature (83%) were the three main clinical features of SDS. Supplementation of pancreatin and component blood transfusion may temporarily alleviate the disease, while allogeneic hematopoietic stem cell transplantation is still an effective radical treatment. The comparative analysis of the Chinese and oversea data showed that compared with those in the European and American countries, the children with SDS in China had significantly higher incidence rates of chronic diarrhea, reductions in peripheral blood cells (three lineages), and liver damage, and there were also differences in the type of mutant genes.

Establishment of a prognostic Nomogram model for predicting the first 72-hour mortality in polytrauma patients / 中华危重病急救医学

Objective:To establish a prognostic Nomogram model for predicting the risk of early death in polytrauma patients.Methods:Data extracted from a polytrauma study on Dryad, an open access database, was selected for secondary analysis. Patients from 18 to 65 years old with polytrauma in the original data were included. All patients with missing variables, such as blood lactic acid (Lac), Glasgow coma score (GCS) and injury severity score (ISS) at admission, were excluded. The differences of gender, age, Lac, ISS and GCS scores between the patients who died within 72 hours and those who survived were analyzed. The risk factors for 72-hour death were analyzed by Logistic regression, and the Nomogram prediction model was established using R software. The receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the model, and the Bootstrap method was used for internal verification by repeating sample for 1 000 times. Decision curve (DCA) was applied to analyze the clinical practical value of the model.Results:A total of 2 315 polytrauma patients were included. Logistic regression analysis showed that Lac, GCS score and age > 55 years old were the risk factors for early death in polytrauma patients [Lac: odds ratio ( OR) = 1.36, 95% confidence interval (95% CI) was 1.29-1.42, P < 0.001; GCS score: OR = 0.76, 95% CI was 0.73-0.79, P < 0.001; age > 55 years old: OR = 1.92, 95% CI was 1.37-2.66, P < 0.001]. The prediction model was established by using the above risk factors and displayed by Nomogram. ROC curve analysis showed that the area under the ROC curve (AUC) of Nomogram model to predict the risk of death within 72 hours was 0.858, and the predictive ability of Nomogram model was significantly higher than that of Lac (AUC = 0.743), GCS score (AUC = 0.774) and ISS score (AUC = 0.699), all P < 0.05. The model calibration chart showed that the predicting probability was consistent with the actual occurrence probability, and the DCA showed that Nomogram model presented excellent clinical value in predicting the 72-hour death risk for polytrauma patients. Conclusions:The prognostic Nomogram model presents significantly predictive value for the risk of death within 72 hours in polytrauma patients. Prognostic Nomogram model could offer individualized, visualized and graphical prediction pattern, and provide physicians with practical diagnostic tool for triage system and management of polytrauma according to precision medicine.