Advances in evolved T7 RNA polymerases for expanding the frontiers of enzymatic nucleic acid synthesis.

In vitro RNA synthesis technologies are crucial in developing therapeutic RNA drugs, such as mRNA vaccines and RNA interference (RNAi) therapies. Enzymatic RNA synthesis, recognized for its sustainability and efficiency, enables the production of extensive RNA sequences under mild conditions. Among the enzymes utilized, T7 RNA polymerase is distinguished by its exceptional catalytic efficiency, enabling the precise and rapid transcription of RNA from DNA templates by recognizing the specific T7 promoter sequence. With the advancement in clinical applications of RNA-based drugs, there is an increasing demand for the synthesis of chemically modified RNAs that are stable and resistant to nuclease degradation. To this end, researchers have applied directed evolution to broaden the enzyme's substrate scope, enhancing its compatibility with non-canonical substrates and reducing the formation of by-products. This review summarizes the progress in engineering T7 RNA polymerase for these purposes and explores prospective developments in the field.

Dietary salt promotes cognitive impairment through repression of SIRT3/PINK1-mediated mitophagy and fission.

Dietary salt is increasingly recognized as an independent risk factor for cognitive impairment. However, the exact mechanisms are not yet fully understood. Mitochondria, which play a crucial role in energy metabolism, are implicated in cognitive function through processes such as mitochondrial dynamics and mitophagy. While mitochondrial dysfunction is acknowledged as a significant determinant of cognitive function, the specific relationship between salt-induced cognitive impairment and mitochondrial health has yet to be fully elucidated. Here, we explored the underlying mechanism of cognitive impairment of mice and N2a cells treated with high-salt focusing on the mitochondrial homeostasis with western blotting, immunofluorescence, electron microscopy, RNA sequencing, and more. We further explored the potential role of SIRT3 in salt-induced mitochondrial dysfunction and synaptic alteration through plasmid transfection and siRNA. High salt diet significantly inhibited mitochondrial fission and blocked mitophagy, leading to dysfunctional mitochondria and impaired synaptic plasticity. Our findings demonstrated that SIRT3 not only promote mitochondrial fission by modulating phosphorylated DRP1, but also rescue mitophagy through promoting PINK1/Parkin-dependent pathway. Overall, our data for the first time indicate that mitochondrial homeostasis imbalance is a driver of impaired synaptic plasticity in a cognitive impairment phenotype that is exacerbated by a long-term high-salt diet, and highlight the protective role of SIRT3 in this process.

Psychometric and structural properties of the traditional Chinese version of the sleep condition indicator for patients undergoing hemodialysis.

PURPOSE: Insomnia is a prevalent sleep disorder among patients undergoing hemodialysis for chronic kidney disease. This study aimed to translate the sleep condition indicator (SCI), an insomnia screening tool based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), into a traditional Chinese version (SCI-TC) and evaluate the reliability and validity of this version for patients undergoing hemodialysis. METHODS: This cross-sectional study conducted from November 2022 to June 2023 involved 200 patients on hemodialysis (mean age, 65.56 years; 61.5% men). Participants completed a series of questionnaires, with insomnia diagnosed according to DSM-5 criteria as the gold standard. A receiver operating characteristic (ROC) curve analysis was conducted to examine the sensitivity and specificity of the SCI-TC. RESULTS: According to the DSM-5 criteria, 38% of the participants had insomnia. Cronbach's alpha for the SCI-TC was 0.92. The SCI-TC exhibited a good fit as a two-factor model, and its scores were significantly associated with those of the traditional Chinese versions of the Insomnia Severity Index, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, EuroQol 5-Dimensions scale, and EuroQol Visual Analogue Scale (r = - 0.94, - 0.53, - 0.38, 0.27, and 0.30, respectively; all p < 0.05). The ROC curve analysis revealed an optimal cutoff of 16 points, with the sensitivity, specificity, and area under curve of 88.2%, 84.7%, and 0.91(95% confidence interval, 0.87-0.95), respectively. CONCLUSION: The SCI-TC demonstrates robust reliability and validity in detecting insomnia among patients undergoing hemodialysis. These findings suggest that health-care providers should considering using the SCI as an easy-to-use tool for the timely detection of insomnia in this population.

Effectiveness of Acupressure for Fatigue Alleviation in Patients Receiving Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Fatigue, a major health concern among patients receiving hemodialysis, is associated with poor quality of life, negative emotions, and cognitive dysfunction. Acupressure is a low-cost and noninvasive traditional Chinese therapy that has been widely used in community and clinic settings. However, the beneficial effects of acupressure on various aspects of fatigue among these patients have not been systematically investigated. PURPOSE: This study was designed to determine the effects of acupressure on fatigue in patients receiving hemodialysis. The moderating influences of bio-sociodemographic characteristics and methodology on the association between acupressure and posthemodialysis fatigue were also examined. METHODS: Four electronic databases were searched for qualified articles published between database inception and November 2, 2022. Only randomized controlled trials designed to investigate the effects of acupressure on fatigue in patients receiving hemodialysis were qualified for consideration. A random-effects model was used for data analysis. RESULTS: Eight randomized controlled trials with 11 effect sizes and 725 participants were included in this study. In these studies, acupressure was found to have a significantly higher alleviation effect on general fatigue (g = -0.78; 95% confidence interval [-1.09, -0.48]) and the behavioral, emotional, sensory, and cognitive domains of fatigue (g = -0.51, -0.51, -0.72, and -0.41, respectively) among patients receiving hemodialysis than those in the control groups. Furthermore, the stimulation of the Shenmen acupoint was found to increase the effects (p < .01) of acupressure on fatigue reduction significantly. Notably, the use of special equipment to perform the acupressure was not found to significantly improve outcomes (p = .99). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Acupressure is effective in alleviating fatigue in patients receiving hemodialysis, particularly when the Shenmen acupoint is used together with other acupoints, and is effective without the application of special equipment. Acupressure may be adopted as a complementary therapy for fatigue alleviation in patients receiving hemodialysis. Based on the findings, healthcare providers should coach patients receiving hemodialysis with fatigue on how to use acupressure therapy appropriately to alleviate this health concern.

Microglia in brain aging: An overview of recent basic science and clinical research developments.

Aging is characterized by progressive degeneration of tissues and organs, and it is positively associated with an increased mortality rate. The brain, as one of the most significantly affected organs, experiences age-related changes, including abnormal neuronal activity, dysfunctional calcium homeostasis, dysregulated mitochondrial function, and increased levels of reactive oxygen species. These changes collectively contribute to cognitive deterioration. Aging is also a key risk factor for neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. For many years, neurodegenerative disease investigations have primarily focused on neurons, with less attention given to microglial cells. However, recently, microglial homeostasis has emerged as an important mediator in neurological disease pathogenesis. Here, we provide an overview of brain aging from the perspective of the microglia. In doing so, we present the current knowledge on the correlation between brain aging and the microglia, summarize recent progress of investigations about the microglia in normal aging, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and then discuss the correlation between the senescent microglia and the brain, which will culminate with a presentation of the molecular complexity involved in the microglia in brain aging with suggestions for healthy aging.

Effects of probiotics combined with dietary intervention on glucose and lipid metabolism and pregnancy outcome in gestational diabetes mellitus / 重庆医学

Objective To investigate the effects of probiotics combined with dietary intervention on pe-ripheral blood glucose and lipid metabolism indicators,placental tissue insulin signaling pathway proteins ex-pression and pregnant outcome in the patients with gestational diabetes mellitus(GDM).Methods A total of 83 patients with GDM in this hospital from December 2021 to December 2022 were selected as the study sub-jects and divided into the probiotics group(probiotics combined with diet intervention,43 cases)and control group(simple diet intervention,40 cases)by the random number table method.The levels of peripheral blood glucose,lipid and insulin resistance related indicators before the intervention and in 8 weeks after the interven-tion were compared between the two groups.The histological changes of placenta were observed by HE stai-ning.The pathological indicators were compared between the two groups.The expression levels of insulin re-ceptor substrate-1(IRS-1),glucose transporter 4(GLUT4)and synaptosome-associated protein of 23 kDa(SNAP23)in placental tissue were detected by immunohistochemistry.The pregnant adverse outcomes were compared between the two groups,and the clinical efficacy of probiotics was evaluated.Results Compared with the control group,the levels of fasting blood glucose(FBG),fasting insulin(FINS),serum triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)in 8 weeks after intervention in the probiotics group were significantly decreased(P＜0.05),and the level of serum high density lipoprotein cholesterol(HDL-C)was significantly increased(P＜0.05).There were no significant differences in the incidence rates of poor villi maturation,thickening of dry villi arterioles and capillary filling in villi interstitial between the two groups(P＞0.05).Compared with the control group,the expression levels of IRS-1,GLUT4 and SNAP23 in placen-tal tissue of the probiotics group were significantly increased(P＜0.05).The incidence rates of neonatal hy-poglycemia and neonatal hyperbilirubinemia in the probiotics group were significantly lower than those in the control group(P＜0.05).Conclusion Compared with simple dietary intervention,probiotics combined with dietary intervention has more advantages in improving glucose and lipid metabolism of GDM patients,moreo-ver reduces the adverse events occurrence in newborns.

Effects of different concentrations of lidocaine infiltration and analgesia in pleural cavity after lung cancer surgery on rehabilitation of patients / 局解手术学杂志

Objective To explore the effects of different concentrations of lidocaine infiltration and analgesia in pleural cavity after lung cancer surgery on rehabilitation of patients.Methods A total of 86 patients with lung cancer were selected and divided into the high concentration group(43 cases)and low concentration group(43 cases)by random number table method.Patients in the high concentration group received injection of 2.0%lidocaine hydrochloride in pleural cavity through the epidural catheter 1st day after surgery,and patients in the low concentration group received injection of 1.5%lidocaine hydrochloride in pleural cavity.In addition,patients in the two groups were treated with patient-controlled intravenous analgesia after surgery.The first time of getting out of bed,first time of exhaustion,first time of defecation and hospital stay after surgery of the two groups were compared.The visual analogue scale(VAS)scores 6 hours,12 hours,24 hours and 48 hours after surgery,the occurrence of agitation during the postoperative awakening period,and the number of analgesic pump compressions and the dosage of analgesic drugs within 24 hours after surgery were compared.The incidence of adverse drug reactions 24 hours after surgery were recorded and the quality of recovery of patients 24 hours after surgery was evaluated by 40-item quality of recovery score(QoR-40).Results The first time of getting out of bed,first time of exhaustion,first time of defecation and hospital stay after operation of patients in the high concentration group were shorter than those in the low concentration group(P<0.05).The VAS scores of the two groups 12 hours and 24 hours after surgery were higher than those 6 hours after surgery(P<0.05),the VAS scores 24 hours and 48 hours after surgery were lower than those 12 hours after surgery(P<0.05),and the VAS scores 48 hours after surgery were lower than those 24 hours after surgery(P<0.05).The VAS scores 6 hours,12 hours,24 hours,and 48 hours after surgery of patients in the high concentration group were lower than those in the low concentration group(P<0.05).The occurrence of agitation during the postoperative awakening period,and the number of analgesic pump compressions and the dosage of analgesic drugs within 24 hours after surgery for patients in the high concentration group were lower/less than those in the low concentration group(P<0.05).There was no significant difference in the total incidence of adverse drug reactions between the two groups(P>0.05).The total QoR-40 score of patients in the high concentration group were higher than those in the low concentration group(P<0.05).Conclusion The use of 2.0%lidocaine infiltration and analgesia in pleural cavity for patients after lung cancer surgery can reduce the agitation during the awakening period,alleviate the postoperative pain,improve the quality of postoperative recovery,and promote the postoperative recovery of the patients,with certain safety.

Machine learning-based speech recognition system for nursing documentation - A pilot study.

PURPOSE: Considering the significant workload of nursing tasks, enhancing the efficiency of nursing documentation is imperative. This study aimed to evaluate the effectiveness of a machine learning-based speech recognition (SR) system in reducing the clinical workload associated with typing nursing records, implemented in a psychiatry ward. METHODS: The study was conducted between July 15, 2020, and June 30, 2021, at Cheng Hsin General Hospital in Taiwan. The language corpus was based on the existing records from the hospital nursing information system. The participating ward's nursing activities, clinical conversation, and accent data were also collected for deep learning-based SR-engine training. A total of 21 nurses participated in the evaluation of the SR system. Documentation time and recognition error rate were evaluated in parallel between SR-generated records and keyboard entry over 4 sessions. Any differences between SR and keyboard transcriptions were regarded as SR errors. FINDINGS: A total of 200 data were obtained from four evaluation sessions, 10 participants were asked to use SR and keyboard entry in parallel at each session and 5 entries were collected from each participant. Overall, the SR system processed 30,112 words in 32,456 s (0.928 words per second). The mean accuracy of the SR system improved after each session, from 87.06% in 1st session to 95.07% in 4th session. CONCLUSION: This pilot study demonstrated our machine learning-based SR system has an acceptable recognition accuracy and may reduce the burden of documentation for nurses. However, the potential error with the SR transcription should continually be recognized and improved. Further studies are needed to improve the integration of SR in digital documentation of nursing records, in terms of both productivity and accuracy across different clinical specialties.

Effectiveness of Cryotherapy on Cancer Therapy-Induced Oral Mucositis: An Umbrella Review.

BACKGROUND: Oral mucositis (OM) considerably affects the experience of patients with cancer during treatment. This study investigated the effects of cryotherapy on cancer therapy-induced OM. OBJECTIVE: This study aimed to systematically appraise evidence on whether cryotherapy can reduce the incidence and severity of OM. METHODS: We conducted an umbrella review to examine the effect of cryotherapy on cancer-related OM. The primary outcome was the incidence and severity of OM. We performed a subgroup analysis including solid cancers and hematological malignancies. RESULTS: Five meta-analyses were included. Cryotherapy could more effectively reduce the incidence of severe OM (risk ratio [RR], 0.37; 95% prediction interval [PI], 0.22-0.64). In the subgroup analyses of solid cancers or hematological malignancies, cryotherapy significantly reduced the incidence of grades 2 to 4 OM in patients with solid cancers (RR, 0.51; 95% PI, 0.34-0.78 and RR, 0.52; 95% PI, 0.36-0.74). However, no significant difference was observed in the incidence of OM in patients with hematological malignancies regarding any grade or grade 3 or 4 OM. Moreover, cryotherapy did not significantly reduce the OM duration (mean difference, -0.13; 95% PI, -20.89 to 20.63; mean difference, -2.99, 95% PI, -8.10 to 2.12). CONCLUSION: Cryotherapy can reduce the incidence of severe OM induced by chemotherapy or radiotherapy. IMPLICATION FOR PRACTICE: We recommend the inclusion of this safe, simple, and convenient intervention in chemotherapy or radiotherapy plans. Additional clinical trials are warranted to extend the limited evidence on the effectiveness of cryotherapy in reducing the severity and duration of OM.

Influence of reinforcement method on the crack characteristic parameters of expansive soil experimental study.

The expansive soil slope is mainly characterized by the decline of slope integrity caused by shallow expansive soil cracking and the destruction of internal soil structure, which seriously affects the overall stability of expansive soil slope. To study the effect of the combination of geogrid reinforcement and slope vegetation on inhibiting the development of expansive soil cracks, six groups of test models were made. The natural dry-wet cycle was simulated, and the crack image was binarized by using image processing technology. The crack characteristic parameters such as crack ratio, crack width, and crack length were extracted, and the effect of various reinforcement methods on inhibiting the development of cracks was comprehensively evaluated. The basic situation of the development of crack indexes in each group with the development of multiple dry-wet cycles was obtained, and the fluctuation changes of crack indexes in different stages were different under different reinforcement methods and dry-wet cycles. At the same time, the influence of different reinforcement methods on the crack development of expansive soil is obtained. It is considered that planting vetiver grass + geogrid backpacking has a good effect on inhibiting the crack development of expansive soil.

Lack of furosemide responsiveness predict severe acute kidney injury after liver transplantation.

Acute kidney injury (AKI) remains to be a common but severe complication after liver transplantation (LT). However, there are still few clinically validated biomarkers. A total of 214 patients who underwent routine furosemide (1-2 mg/kg) after LT were retrospectively included. The urine output during the first 6 h was recorded to evaluate the predictive value of AKI stage 3 and renal replacement therapy (RRT). 105 (49.07%) patients developed AKI, including 21 (9.81%) progression to AKI stage 3 and 10 (4.67%) requiring RRT. The urine output decreased with the increasing severity of AKI. The urine output of AKI stage 3 did not significantly increase after the use of furosemide. The area under the receiver operator characteristic (ROC) curves for the total urine output in the first hour to predict progression to AKI stage 3 was 0.94 (p < 0.001). The ideal cutoff for predicting AKI progression during the first hour was a urine volume of less than 200 ml with a sensitivity of 90.48% and specificity of 86.53%. The area under the ROC curves for the total urine output in the six hours to predict progression to RRT was 0.944 (p < 0.001). The ideal cutoff was a urine volume of less than 500 ml with a sensitivity of 90% and specificity of 90.91%. Severe AKI after liver transplantation seriously affects the outcome of patients. Lack of furosemide responsiveness quickly and accurately predict AKI stage 3, and patients requiring RRT after the operation.

Burned-out testicular germ cell tumors: a clinicopathological analysis of three cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 μg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.

Level of serum FABP1 and its relationship with Helicobacter pylori infection in patients with gastric cancer / 国际肿瘤学杂志

Objective:To investigate the serum level of fatty acid binding protein 1 (FABP1) and its relationship with Helicobacter pylori (Hp) infection in patients with gastric cancer. Methods:Forty gastric cancer patients (gastric cancer group) who were hospitalized in Affiliated Hospital of Qinghai University from August 2021 to August 2022 were selected as the research subjects, and 40 physical examination subjects during the same period were selected as the normal control group and 40 chronic atrophic gastritis patients were selected as the CAG group. The Hp infection were detected by 13C breath test, and the levels of serum FABP1 were detected by enzyme-linked immunosorbent assay. The Hp infection status, serum FABP1 levels, and the relationship between the two in the three groups of study subjects were analyzed. And the relationships between the level of serum FABP1 and the clinicopathological features of gastric cancer patients were analyzed. The diagnostic value of serum FABP1, CA19-9, CA72-4 and combined test of 3 indexes were evaluated by receiver operating characteristic (ROC) curve. Results:The Hp infection rates in the control group, CAG group, and gastric cancer group were 32.50% (13/40), 55.00% (22/40), and 60.00% (24/40), respectively, with a statistically significant difference ( χ2=6.87, P=0.032). Among them, the Hp infection rate in the control group was compared with that in the gastric cancer group, with a statistically significant difference ( P<0.05), and there were no statistically significant differences between the CAG group and the control group, the gastric cancer group (both P>0.05). The levels of serum FABP1 in the control group, CAG group, and gastric cancer group were [63.47 (37.53, 71.59) ] ng/ml, [65.26 (51.15, 79.67) ] ng/ml, and [72.84 (53.44, 82.25) ] ng/ml, respectively, with a statistically significant difference ( H=6.62, P=0.037). Among them, there was a statistically significant difference between the control group and the gastric cancer group ( H=19.93, P=0.031), while there were no statistically significant differences between the CAG group and the control group, the gastric cancer group ( H=1.50, P=0.133; H=1.09, P=0.277). Among all study subjects, the levels of serum FABP1 in the Hp positive group ( n=59) and Hp negative group ( n=61) were [77.05 (68.90, 83.54) ] ng/ml and [47.80 (37.76, 63.32) ] ng/ml, respectively, with a statistically significant difference ( Z=7.45, P<0.001). In the control group, the levels of FABP1 in the serum of Hp positive and Hp negative persons were [77.34 (68.84, 86.31) ] ng/ml and [39.79 (36.83, 63.75) ] ng/ml, respectively, with a statistically significant difference ( Z=4.46, P<0.001). In the CAG group, the levels of FABP1 in the serum of Hp positive and Hp negative patients were [76.51 (65.30, 80.97) ] ng/ml and [49.34 (39.92, 59.41) ] ng/ml, respectively, with a statistically significant difference ( Z=4.32, P<0.001). In the gastric cancer group, the levels of FABP1 in the serum of Hp positive and Hp negative patients were [77.15 (72.62, 84.13) ] ng/ml and [50.57 (44.54, 68.97) ] ng/ml, respectively, with a statistically significant difference ( Z=4.32, P<0.001). There were significant correlations between the serum level of FABP1 and smoking ( t=2.54, P=0.015), tumor diameter ( t=2.23, P=0.035), and lymph node metastasis ( t=3.22, P=0.003) in gastric cancer patients. And there were no significant correlations between FABP1 and gender ( t=0.98, P=0.333), age ( t=1.60, P=0.117), alcohol consumption ( Z=0.10, P=0.925), tumor site ( F=1.06, P=0.356), degree of differentiation ( t=0.61, P=0.545), the depth of infiltration ( t=1.41, P=0.166), distant metastasis ( Z=1.96, P=0.050) and TNM staging ( Z=0.66, P=0.508). ROC curve analysis showed that the area under the curve (AUC) of serum FABP1 for gastric cancer diagnosis was 0.62, 95% CI: 0.51-0.72, the sensitivity and specificity were 57.50% and 68.70%, respectively; the AUC of CA19-9 for gastric cancer diagnosis was 0.89, 95% CI: 0.83-0.95, the sensitivity and specificity were 77.50%, 86.30%, respectively; the AUC of CA72-4 for gastric cancer diagnosis was 0.88, 95% CI: 0.81-0.94, the sensitivity and specificity were 70.00%, 93.70%, respectively; the AUC of combined test of 3 indexes for gastric cancer diagnosis was 0.91, 95% CI: 0.82-0.97, the sensitivity and specificity were 67.50% and 95.00%, respectively. Conclusion:The Hp infection rate of gastric cancer patients is higher than that of the health examiners, the serum FABP1 level of gastric cancer patients is higher than that of the healthy health examiners, the serum FABP1 level of Hp positive persons is higher than that of Hp negative persons, and Hp infection and FABP1 level may have a common carcinogenic mechanism in the occurrence and development of gastric cancer.

Clinical efficacy and anti-inflammation/anti-fibrosis effect of tripterygium glycosides in the treatment of diabetic nephropathy / 中国临床药理学与治疗学

AIM: To observe the clinical efficacy of multi -glycoside of tripterygium wilfordii (GTW) on diabetic nephropathy. METHODS: Fifty-one patients with diabetic kidney disease (DKD) with a history of GTW dosing admitted to the outpatient clinic of Yijishan Hospital affiliated to Wannan Medical College from June 2019 to October 2022 were selected as study subjects, and were followed up regularly to observe the changes in laboratory indexes before and after GTW dosing and adverse drug reactions after 6 months of treatment. The t-test, Mann-Whitney U-test or χ

A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors / 中华肿瘤杂志

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

Geographic Variations in the Prevalence, Awareness, Treatment, and Control of Dyslipidemia among Chinese Adults in 2018-2019: A Cross-sectional Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China.@*METHODS@#A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses.@*RESULTS@#The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001).@*CONCLUSION@#Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.

A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors / 中华肿瘤杂志

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells / 中华肿瘤杂志

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.

Branched-chain amino acids supplementation has beneficial effects on the progression of liver cirrhosis: A meta-analysis.

BACKGROUND: Liver cirrhosis (LC) is currently the 11th most common cause of death and 15th cause of morbidity globally. The treatment of LC is mainly aimed at etiological intervention, lifestyle intervention, prevention and treatment of complications and nutritional treatment. Nutritional treatment of LC mainly includes increasing dietary intake, food intake time and branched-chain amino acids (BCAAs). Despite the recommendation of BCAAs in some guidelines, adverse effects have been reported in studies so the efficacy and safety of BCAAs remain controversial. Currently, BCAAs have been widely used in chronic liver disease, while the summary of the effect of BCAAs on long-term prognosis is rare. AIM: To determine the effects of BCAAs in patients with LC. METHODS: The PubMed, Cochrane Library, Embase and Web of Science databases were searched. The retrieval deadline was 1 October 2021 and there were no language restrictions set in the retrieval. The study was performed in strict accordance with the inclusion and exclusion criteria. Nine studies were finally included. The primary outcome was complications of LC. The secondary outcomes were nutritional status and liver function. This meta-analysis used the Review Manager, version 5 statistical package (Cochrane Collaboration, Oxford, England) for analysis. RESULTS: The analysis included nine studies that consisted of 1080 patients (554 in the BCAA groups and 526 in the control groups). The nine studies were randomized control trials (RCTs). The quality of the studies was assessed using the risk of bias method recommended by the Cochrane Collaboration. BCAAs reduced the rate of complications in LC patients [Risk ratio: 0.70, 95% confidence interval (CI): 0.56-0.88, P = 0.002] and improved patients' albumin levels [std mean difference SMD: 0.26, 95%CI: 0.12-0.40, P = 0.0002]. Meanwhile, BCAAs significantly ameliorated the levels of alanine transaminase (SMD: -2.03, 95%CI: -2.52 to -1.53, P < 0.00001) and aspartate aminotransferase (SMD: -1.8, 95%CI: -2.14 to -1.46, P < 0.00001). Meanwhile, glucose in the LC was significantly increased in BCAA-treated patients (MD: 13.04, 95%CI: 6.81-19.89, P = 0.0002). CONCLUSION: BCAAs reduce the incidence of complications in patients with LC and ameliorate nutritional status.