Bibliometric analysis of drug package insert adaptation for the elderly based on Web of Science / 中国药房

OBJECTIVE To explore the hotspots of aging adaptation of drug package inserts， and to provide evidence for the development of aging adaptation of drug package inserts in China. METHODS The relevant English literature on drug package inserts for the elderly published from 2012 to 2022 was retrieved from Web of Science Core Collection； bibliometric analysis was performed by using VOSviewer and CiteSpace software， to explore research hotspots in this field， and summarize obstacles and solutions for the development of this field. RESULTS & CONCLUSIONS This study collected a total of 335 literature related to the aging adaption of drug package inserts， from 819 research institutions in 51 countries （regions）， involving 2 174 authors. The research development of drug package insert adaptation for the elderly has slowed down in the past decade， and developed countries such as the United States and Japan dominate this field. Authors such as Wolf from Northwestern University in the United States， have the largest number of publications（12 literature）. The research focuses in this field include the risk management of medication for the elderly， the updating of medication information for the elderly in drug package inserts， and the understanding and compliance of the elderly with drug package inserts and their influencing factors. The solutions to related obstacles in the development of aging adaption in drug package inserts include improving the visibility and readability of drug package inserts， filling in the information on elderly medication in drug package inserts， and so on. China can learn from the experiences and methods of other countries， conduct investigations into the influencing factors of elderly package inserts and pharmacokinetic studies based on the characteristics of the Chinese population， and improve the safety of medication for elderly patients in multiple dimensions.

Glycyrrhizic acid alleviates cisplatin-induced ototoxicity by inhibiting in-flammation of cochlear in C57BL/6J mice / 中国病理生理杂志

AIM:To study whether glycyrrhizic acid(GL)can resist the ototoxicity of cisplatin(CDDP)in mice and its molecular mechanism.METHODS:Male C57BL/6J mice were divided into 5 groups:control group,DMSO(5%)group,CDDP(4 mg/kg)group,CDDP+low-dose(50 mg/kg)GL group,and CDDP+high-dose(100 mg/kg)GL group(n=14).Auditory brainstem response(ABR)was used to detect hearing changes of mice.HE staining was used to observe the morphological change of cochlear stria vascular in mice.Evans blue(EB)staining was used to observe the per-meability change of the blood-labyrinth barrier(BLB).Immunohistochemical technique was used to detect the expression and distribution of adhesion protein VE-cadherin and tight junction protein ZO-1 on the cochlear stria.ELISA assay and immunofluorescence technology were employed to detect the expression of tumor necrosis factor-α(TNF-α)and interleu-kin-1β(1L-1β).RESULTS:In CDDP group,ABR waveforms of all frequencies were disturbed,the hearing threshold was significantly increased,and I wave latency was prolonged(P＜0.05).In CDDP+GL group,ABR waveforms of various frequencies were well differentiated,the hearing threshold was significantly decreased,and the latency of I-wave was shortened(P＜0.01).The disordered morphology and more vacuoles in the stria vascularis were observed by HE staining in CDDP group.The GL alleviated CDDP-induced damage in the stria vascularis.In EB staining,CDDP caused an increase in per-meability of BLB(P＜0.01),which was improved by GL treatment(P＜0.01).Immunohistochemical results showed that the expression of VE-cadherin and ZO-1 in CDDP group were decreased(P＜0.01),which was restored in CDDP+GL group(P＜0.01).The ELISA and immunofluorescence results showed that the expression of IL-1β and TNF-α was in-creased after CDDP treatment(P＜0.01),which was restored in CDDP+GL group(P＜0.01).CONCLUSION:The GL alleviates CDDP-induced hearing loss in mice by inhibiting CDDP-induced inflammation and reducing the permeability of BLB.

The Correlation between Traditional Chinese Medicine Constitution and the Progression of Abnormal Glucose Metabolism in Community Population： A Case-control Study / 中医杂志

ObjectiveTo investigate the role of traditional Chinese medicine （TCM） constitution in the progression of abnormal glucose metabolism among community population. MethodsA total of 393 community residents who participated in community diabetes screening from 2019 to 2021 and had complete physical examination data at baseline and at the 2nd year follow-up were selected. According to the results of glucose tolerance tests， community residents were divided into the abnormal glucose metabolism progression group and non-progression group， and were matched at the ratio of 1∶2 using the propensity score matching. The influencing factors related to diabetes at baseline were collected for both groups. The traditional Chinese medicine constitution was determined among population in two groups. The differences of influencing factors and traditional Chinese medicine constitution between the two groups were compared. Logistic regression analysis was used to analyze the risk factors for the progression of abnormal glucose metabolism. ResultsFinally， 131 patients were included in the progression group and 262 patients in the non-progression group. Compared to the non-progression group， the progression group had significantly higher proportion of hyperlipidemia history ， hyperglycemia history， phlegm-dampness constitution， and blood stasis constitution （P＜0.05 or P＜0.01）. Univariate logistic regression analysis revealed that the history of hyperlipidemia （P=0.011）， history of hyperglycemia （P＜0.001）， the family history of diabetes （P＜0.001）， yin-deficiency constitution （P=0.047）， phlegm-dampness constitution （P=0.011） and blood-stasis constitution （P=0.008） were risk factors for the progression of abnormal glucose metabolism. Multivariate logistic regression analysis indicated that the history of hyperglycemia （P＜0.001）， yin-deficiency constitution （P=0.026） and blood-stasis constitution （P=0.032） were independent risk factors for the progression of abnormal glucose metabolism. ConclusionThe history of hyperglycemia， yin-deficiency constitution and blood-stasis constitution may be the risk factors for the progression of abnormal glucose metabolism.

Historical Evolution and Modern Research Progress of Processing of Notoginseng Radix et Rhizoma / 中国实验方剂学杂志

By reviewing the relevant literature of ancient herbal works and modern codices， this paper sorted out the historical evolution and developmental venation of processing of Notoginseng Radix et Rhizoma. On this basis， the modern research of processed products of Notoginseng Radix et Rhizoma was used as the breakthrough point to analyze the literature in terms of processing technology， chemical composition changes and changes in pharmacological effects before and after processing. According to the research status of processing of Notoginseng Radix et Rhizoma， some existing problems were analyzed in this paper， such as not many ancient processing methods used in modern time， lack of standardized research on processing technology. And saponins， polysaccharides， amino acids， flavonoids and other chemical components in Notoginseng Radix et Rhizoma may change to different degrees before and after processing， which was the main reason for the difference of efficacy before and after processing. However， the current research on the pharmacological effects of Notoginseng Radix et Rhizoma mainly focuses on raw products， resulting in a lack of in-depth research on the transformation mechanism of Notoginseng Radix et Rhizoma in processing difference， and the scientific connotation of "Shengxiao Shubu" has not been clearly elaborated， which is not conducive to the standardized clinical use of drugs. Therefore， it is necessary to further analyze the material basis of Notoginseng Radix et Rhizoma and its processed products， and to explore the change rule of chemical components before and after processing and its correlation with pharmacodynamic activity， so as to clarify the processing mechanism for providing scientific basis for its standardized processing， quality control and clinical rational use.

Forsythiaside B inhibits cerebral ischemia/reperfusion-induced oxidative stress injury in mice via the AMPK/DAF-16/FOXO3 pathway / 南方医科大学学报

OBJECTIVE@#To study the protective effect of forsythiaside B (FB) against cerebral oxidative stress injury induced by cerebral ischemia/reperfusion (I/R) in mice and explore the underlying mechanism.@*METHODS@#Ninety C57BL/6 mice were randomized into sham-operated group, middle cerebral artery occlusion (MCAO) model group, and low-, medium and highdose (10, 20, and 40 mg/kg, respectively) FB groups. The expression levels of MDA, ROS, PCO, 8-OHdG, SOD, GSTα4, CAT and GPx in the brain tissue of the mice were detected using commercial kits, and those of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 were detected with Western blotting. Compound C (CC), an AMPK inhibitor, was used to verify the role of the AMPK pathway in mediating the therapeutic effect of FB. In another 36 C57BL/6 mice randomized into 4 sham-operated group, MCAO model group, FB (40 mg/kg) treatment group, FB+CC (10 mg/kg) treatment group, TTC staining was used to examine the volume of cerebral infarcts, and the levels of ROS and SOD in the brain were detected; the changes in the protein expressions of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 in the brain tissue were detected using Western blotting.@*RESULTS@#In mice with cerebral IR injury, treatment with FB significantly reduced the levels of ROS, MDA, PCO and 8-OHdG, increased the activities of antioxidant enzymes SOD, GSTα4, CAT and GPx, and enhanced phosphorylation of AMPK and FOXO3 and DAF-16 protein expression in the brain tissue (P < 0.01). Compared with FB treatment alone, the combined treatment with FB and CC significantly reduced phosphorylation of AMPK and FOXO3, lowered expression of DAF-16 and SOD activity, and increased cerebral infarction volume and ROS level in the brain tissue of the mice (P < 0.01).@*CONCLUSION@#FB inhibits oxidative stress injury caused by cerebral I/R in mice possibly by enhancing AMPK phosphorylation, promoting the downstream DAF-16 protein expression and FOXO3 phosphorylation, increasing the expression of antioxidant enzymes, and reducing ROS level in the brain tissue.

Correlation between serum albumin and outcomes of successful recanalization after mechanical thrombectomy in patients with anterior circulation ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between serum albumin and hypoalbuminemia (HA) and the outcome after endovascular mechanical thrombectomy (EMT) in patients with stroke caused by acute anterior circulation large vessel occlusion.Methods:Stroke patients caused by acute anterior circulation large vessel occlusion received EMT treatment at the Department of Emergency Stroke, the Affiliated Hospital of Jining Medical University from June 2020 to August 2022 were retrospectively included. The demographic information, baseline clinical data, endovascular treatment parameters, and clinical outcomes of the patients were collected. HA was defined as serum albumin <35 g/L within 24 h of admission, and poor outcome was defined as the modified Rankin Scale score >2 at 90 d after onset. Multivariate logistic regression analysis was used to identify the independent influencing factors for poor outcomes. Results:A total of 177 patients were included, with a median age of 66 years, and 126 (71.19%) were males. Thirty-nine patients (22.03%) had HA, and 119 (67.23%) had poor outcomes. The proportion of pulmonary infection in the HA group was significantly higher than that in the non-HA group ( P<0.05). Multivariate logistic regression analysis showed that lower serum albumin (odds ratio [ OR] 4.102, 95% confidence interval [ CI] 1.316-16.451; P=0.028), postprocedural neurological deterioration ( OR 6.326, 95% CI 1.263-48.318; P=0.042) and pulmonary infection ( OR 5.873, 95% CI 1.028-24.452; P=0.018) were significantly independently associated with the poor outcomes. Conclusions:The HA group has a higher incidence of postprocedural pulmonary infection. Lower serum albumin, postprocedural neurological deterioration and pulmonary infection are the independent risk factors for the poor outcomes in patients with anterior circulation ischemic stroke who had successful recanalization after EMT.

Influencing factors of anastomotic leakage after laparoscopic intersphincter resection for extremely low rectal cancer and construction of nomogram prediction model / 中华消化外科杂志

Objective:To investigate the influencing factors of anastomotic leakage after laparoscopic intersphincter resection (ISR) for extremely low rectal cancer and construction of nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 812 patients who underwent laparoscopic ISR for extremely low rectal cancer in the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) from February 2012 to February 2022 were collected. There were 459 males and 353 females, aged (51±11)years. Observation indicators: (1) surgical situations; (2) follow-up; (3) influencing factors of postoperative anastomotic leakage; (4) construction and evaluation of nomogram prediction model for postoperative anastomotic leakage. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. The COX proportional hazard model was used for univariate and multivariate analyses. The R software(3.5.1 version) was used to construct nomogram prediction model. The receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was used to evaluate the efficacy of the nomogram prediction model. The Bootstrap method was used for internal verification and to calculate the average consistency index (C-index). Results:(1) Surgical situations. All 812 patients underwent laparoscopic ISR for extremely low rectal cancer, including 388 cases undergoing partial ISR, 218 cases undergoing subtotal ISR and 206 cases undergoing complete ISR. All 812 patients underwent ileal protective ostomy, and there were 306 cases with double anastomosis and 203 cases with left colic artery preserved, respectively. The operation time and volume of intraoperative blood loss of 812 patients was (179±33)minutes and (33±13)mL, respectively. (2) Follow-up. All 812 patients were followed up for (13.5±0.9)months. Of the 812 patients, there were 62 cases with postoperative anastomotic leakage and the healing time of these cases was (33±6)days. (3) Influencing factors of postoperative anastomotic leakage. Results of multivariate analysis showed that male, neoadjuvant chemoradiotherapy, failure of reser-ving left colic artery were independent risk factors of anastomotic leakage after laparoscopic ISR for extremely low rectal cancer ( hazard ratio=5.98, 4.00, 16.26, 95% confidence interval as 1.66-24.12, 1.30-12.42, 3.00-90.89, P<0.05). (4) Construction and evaluation of nomogram prediction model for postoperative anastomotic leakage. According to the results of multivariate analysis, male, neoadju-vant chemoradiotherapy and failure of reserving left colic artery were used to construct the nomogram prediction model for anastomotic leakage after laparoscopic ISR for extremely low rectal cancer, and the score of these indexes in the nomogram prediction model was 50, 49, 93, respectively. The total score of these index corresponded to the incidence rate of anastomotic leakage. Results of ROC curve showed that the AUC of nomogram prediction model of anastomotic leakage after laparoscopic ISR for extremely low rectal cancer was 0.87 (95% confidence interval as 0.80-0.93, P<0.05), with sensi-tivity and specificity 0.96 and 0.60, respectively. Results of internal verification showed that the C-index of nomogram prediction model was 0.87. Conclusion:Male, neoadjuvant chemoradiotherapy, failure of reserving left colic artery are independent risk factors of anastomotic leakage after laparo-scopic ISR for extremely low rectal cancer, and the nomogram prediction model based on these indexes can predict the incidence rate of postoperative anastomotic leakage.

Digital and 3D printing technologies in design of superficial iliac circumflex artery flap for coverage of donor site of anterolateral thigh flap: Report of 8 cases / 中华显微外科杂志

Objective:To explore the efficacy of digital and 3D printing technologies on design of superficial iliac circumflex artery flap for coverage the donor site of anterolateral thigh flap(ALTF).Methods:Clinical data of 8 patients were studied retrospectively for treatment of soft tissue defects of hand in the Department of Hand Surgery, Wuxi NO.9 People's Hospital Affiliated to Soochow University, from April 2017 to October 2021. The patients were 6 males and 2 females, aged from 29 to 59 years(mean, 45.8 years). Cause of injury: 3 patients were crushed, 2 by hot pressing, and 3 by machine strangulation. Site of injury included: 5 cases were dorsal hand defects and 3 cases were palm defects. All the wounds were contaminated to varying degrees with soft tissue defects. The areas of soft tissue defect ranged from 11 cm×10 cm to 22 cm×14 cm. Four patients had combined injuries of open fracture of metacarpals and phalanges and 3 with tendon defects. All wounds were repaired by free ALTF transplantation. And the donor sites in the thigh were repaired by superficial iliac circumflex artery flaps. The secondary wounds caused by flap harvesting on abdominal wall were closed directly. The targeted perforator vessels were detected preoperatively by CTA combined with CDU. 3D printed models of the affected hand were obtained before operation for individualised repairs according to the shape and area of the wounds. After the operation, all patients entered scheduled follow-ups at the outpatient clinic and via internet by observing the flap shape and testing the recovery of sensory and movement of adjacent joint.Results:The shapes and sizes of the wounds and the flaps were found basically in accordance with those in the preoperative simulative designs. All flaps in 8 patients survived and the wounds healed completely. All patients entered follow-ups for 8 to 24(average, 17.5) months. The donor thighs presented good appearance and colour, pliability without bloating. The range of motion of the hips and knees was not affected. Only linear scars remained in the abdominal donor sites, with natural colour and appearance.Conclusion:Digital and 3D printing technologies in preoperative design of flaps can help to locate the perforator vessels intraoperatively and guide the individualised design of the flaps with improved operation efficiency and satisfactory appearance of the flaps.

Postoperative hypoalbuminemia in patients with acute ischemic stroke with successful recanalization by endovascular therapy: risk factors and their impact on outcomes / 国际脑血管病杂志

Objective:To investigate the risk factors of hypoalbuminemia (HA) in patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) after endovascular mechanical thromboectomy (EMT) and impact on outcomes.Methods:Patients first diagnosed with anterior circulation LVO-AIS and underwent emergency EMT at the Department of Acute Stroke, the Affiliated Hospital of Jining Medical University from June 1, 2020 to April 31, 2023 were retrospectively included. According to the first follow-up serum albumin examination after procedure (6-8 d), the patients were divided into HA group (<35 g/L) and non-HA group (≥35 g/L). According to the modified Rankin Scale score at 90 d after EMT, the patients were divided into a good outcome group (0-2) and a poor outcome group (3-6). Univariate and multivariate logistic analysis was used to determine independent risk factors for HA after EMT and their impact on outcomes. Results:A total of 144 patients were enrolled, including 107 males (74.30%) with a median age of 64 years (interquartile range, 56-71 years). There were 50 patients (34.72%) in the HA group and 94 (65.28%) in the non-HA group; 60 (41.67%) in the good outcome group, and 84 (58.33%) in the poor outcome group. Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.061, 95% confidence interval [ CI] 1.014-1.111; P=0.011) and pulmonary infection ( OR 5.136, 95% CI 1.917-13.760; P=0.001) were independent risk factors for HA; HA ( OR 4.345, 95% CI 1.367-13.814; P=0.013), pneumonia ( OR 5.113, 95% CI 1.217-12.528; P=0.026), and onset to reperfusion time ( OR 5.473, 95% CI 1.090-16.05; P=0.038) were independent risk factors for poor outcomes. Conclusions:Age and pulmonary infection are independent risk factors for HA in LVO-ASI patients after EMT, and HA is the independent risk factor for poor outcomes of the patients.

Study on effects of Jianpi Qinghua Decoction on hepatocyte apoptosis in nonalcoholic fatty liver disease model mice / 国际中医中药杂志

Objective:To study the effects of Jianpi Qinghua Decoction on hepatocyte apoptosis under non-alcoholic fatty liver disease (NAFLD), and to discuss its mechanism.Methods:Totally 29 C57 mice were randomly selected and fed a 60% high fat diet for 16 weeks, while the remaining 6 mice were given regular feed as the normal group. After successful modeling, 12 mice with larger body weight were divided into TCM group and model group using a random number table method, while continuing to receive high-fat feed. The TCM group was orally administered Jianpi Qinghua Decoction 20.961 g/kg. The normal group and model group were orally administered an equal volume of distilled water once a day, with continuous intervention for 4 weeks. The levels of GOT and GPT in blood were detected by ELISA, the deposition of triglyceride in liver was detected by oil red O, and the apoptosis of liver cells was detected by TUNEL fluorescence staining. Western blot was used to detect the expressions of cleaved Caspase-3, Caspase-3, Bax, Bcl-2, JNK and p-JNK.Results:Compared with the model group, the body weight and GPT in the TCM group significantly decreased ( P<0.05), TG deposition was significantly reduced, apoptosis range of liver cells was significantly reduced, and cleaved Caspase-3/Caspase-3, p-JNK/JNK and the expression of Bax significantly decreased ( P<0.05). The expression of Bcl-2 increased ( P<0.05). Conclusion:Jianpi Qinghua Decoction can inhibit JNK protein phosphorylation and effectively reduce liver cell apoptosis in NAFLD mice, which may delay the progression of NAFLD towards cirrhosis and liver cancer.

Construction and application value of nomogram predictive model for the prognosis of rectal cancer liver metastases based on SEER database / 中华消化外科杂志

Objective:To investigate the construction and application value of a nomogram predictive model for the prognosis of rectal cancer liver metastases based on Surveillance, Epidemio-logy, and End Results (SEER) database.Methods:The retrospective cohort study was conducted. The clinicopathological data of 6 192 patients with rectal cancer liver metastases in the SEER database ( http://seer.cancer.gov/) and 312 patients who were admitted to The Second Affiliated Hospital of Naval Medical University January 2010 to December 2016 were collected. Of 6 192 patients, there were 3 592 males and 2 600 cases. There were 1 076 cases with age lower than 50 years, 2 862 cases with age as 50-69 years, 2 254 cases with age equal to or more than 70 years, respectively. Of 312 pati-ents, there were 177 males and 135 cases. There were 51 cases with age lower than 50 years, 155 cases with age as 50-69 years, 109 cases with age equal to or more than 70 years, respectively. Patients of the SEER database were set as the training set, and patients in The Second Affiliated Hospital of Naval Medical University were set as the validation set. Univariate and multivariate COX proportional hazards regression models were used to analyze risk factors associated with prognosis, and construct and verify the accuracy of nomogram predictive model for the prognosis of rectal cancer liver metas-tasis. The training set were used to construct the nomogram prediction model, and the validation set were used to verify its performance. Observation indicators: (1) prognostic factors analysis in patients with rectal cancer liver metastases; (2) construction and verificative of the predictive model for the prognosis of rectal cancer liver metastasis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed using the rank sum test. The COX regression model was used for univariate and multivariate analyses. Kaplan-Meier method was used to calculate survival rates, and Log-Rank test was used for survival analysis. Results:(1) Prognostic factors analysis in patients with rectal cancer liver metastases. Results of multivariate analysis showed that age >50 years, TNM Ⅱ-Ⅳ stage, stage T3-T4, stage N1-N2, the number of lymph nodes dissected <12, tumor diameter >5.1 cm, positive carcinoembryonic antigen, peripheral nerve infiltration, radiotherapy and adjuvant chemotherapy, poorly differentiated or undifferented tumor were independent prognostic factors of patients ( P<0.05). (2) Construction and verification of the predictive model for the prognosis of rectal cancer liver metastasis. A nomogram predictive model for the prognosis of rectal cancer liver metastasis was constructed based in the multivariate analysis. The C-index of the nomogram predictive model was 0.91, with area under the curve as 0.726, indicating a good discriminant ability. Results of the calibration curve in validation dataset showed that the colorectal cancer survival rate predicted by the nomogram predictive model was consistent with the actual survival rate. Conclusion:The nomogram predictive model can accurately predict the survival probability of patients with rectal cancer liver metastases.

The value of cystatin C in early diagnosis of acute kidney injury and predicting prognosis after radical nephrectomy / 中华泌尿外科杂志

Objective:To investigate the value of cystatin C (Cys-C) in the early diagnosis of acute kidney injury (AKI) after radical nephrectomy and the predictive value for the prognosis of Cys-C based estimated glomerular filtration rate (eGFR Cys-C) after surgery. Methods:The clinical data of 118 patients who underwent unilateral radical nephrectomy in our hospital from January 2019 to December 2020 were retrospectively analyzed. According to the diagnostic criteria of AKI, they were divided into AKI group of 75 cases and no-AKI group of 43 cases. AKI group was (62.7±10.7) years old, with 49 males and 26 females. The no-AKI group was (62.3±12.8) years old, with 21 males and 22 females. The urea nitrogen was (4.9±1.3) mmol/L, creatinine (75.7±14.5)μmol/L, Cys-C (0.85±0.22) mg/L, eGFR Cr(76.3±11.2)ml/(min·1.73m 2), and eGFR Cys-C(101.4±17.4)ml/(min·1.73m 2)in AKI group before operation.In no-AKI group, preoperative urea nitrogen was (4.9±1.5) mmol/L, creatinine (74.5±13.1)μmol/L, Cys-C (0.81±0.29) mg/L, eGFR Cr(78.6±12.5)ml/(min·1.73m 2), and eGFR Cys-C(99.3±18.8)ml/(min·1.73m 2), and there were no significant differences in the values of urea nitrogen, creatinine, Cys-C and eGFR between the two groups before surgery ( P>0.05). ROC curve was used to analyze the diagnostic value of urea nitrogen, creatinine, Cys-C, eGFR calculated based on creatinine and Cys-C at 48h after surgery, and binary Logistic regression was used to analyze the risk factors for AKI. The creatinine status of patients diagnosed with SPS was evaluated 6 months after surgery, based on the definition of Cys-C based eGFR being less than 70% of creatinine-based eGFR(SPS=eGFR Cys-C/ eGFR Cr≤0.7). Results:In AKI group, creatinine was(115.2±22.1)μumol/L, Cys-C (1.8±0.27) mg/L, eGFR Cr (51.6±9.6)ml/(min·1.73m 2), and eGFR Cys-C(43.4±8.5)ml/(min·1.73m 2)48 h after operation. The creatinine was(92.7±13.3)μmol/L, Cys-C(1.3±0.23) mg/L, eGFR Cr(62.2±11.3)ml/(min·1.73m 2), and eGFR Cys-C(61.5±9.5)ml/(min·1.73m 2) in no-AKI group, and difference were statistically significant between the two groups ( P<0.01). ROC curve was used to analyze the diagnosis of AKI. Creatinine, Cys-C, eGFR Cr and eGFR Cys-Cwere all of diagnostic value for AKI (all P<0.01), and AUC(Area under curve) were 0.809, 0.889, 0.761 and 0.925 respectively. The sensitivity, specificity and area under the curve of eGFR Cys-C were 93.3%, 74.4% and 92.5% respectively. Binary Logistic regression analysis showed that creatinine( OR=10.851, 95% CI 2.322-50.688, P=0.004), Cys-C( OR=10.016, 95% CI 2.306-43.362, P=0.001), eGFR Cr( OR=17.923, 95%CI 3.216-53.172, P=0.001) and eGFR Cys-C( OR=19.817, 95% CI 3.367-55.263, P=0.001)were all independent risk factors for AKI. The predictive accuracy of eGFR Cys-C, creatinine, Cys-C, eGFR Cr were 91.6%, 85.7%, 90.2%, 88.5%, respectively. There were 15 cases were confirmed SPS in the AKI group, and only 2 cases were confirmed SPS in the no-AKI group, indicating patients in the AKI group developed more SPS than those in the no-AKI group, with statistically significant difference(Kappa value was 5.22, P=0.02). The 6-month follow-up showed that the creatinine of confirmed SPS was (103.8±23.4)μmol/L and the creatinine of unconfirmed SPS was (86.8±27.2)μmol/L, with statistically significant difference ( P<0.01). Conclusions:eGFR Cys-C calculated based on Cys-C has high sensitivity in diagnosing AKI and has early diagnostic value. Patients diagnosed with SPS based on eGFR Cys-C had higher creatinine 6 months after surgery.

Specific Mutations in APC, with Prognostic Implications in Metastatic Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Loss-of-function mutations in the adenomatous polyposis coli (APC) gene are common in metastatic colorectal cancer (mCRC). However, the characteristic of APC specific mutations in mCRC is poorly understood. Here, we explored the clinical and molecular characteristics of N-terminal and C-terminal side APC mutations in Chinese patients with mCRC. @*Materials and Methods@#Hybrid capture-based next-generation sequencing was performed on tumor tissues from 275 mCRC pati-ents to detect mutations in 639 tumor-associated genes. The prognostic value and gene-pathway difference between APC specific mutations in mCRC patients were analyzed. @*Results@#APC mutations were highly clustered, accounting for 73% of all mCRC patients, and most of them were truncating mutations. The tumor mutation burden of the N-terminal side APC mutations group (n=76) was significantly lower than that of the C-terminal side group (n=123) (p < 0.001), further confirmed by the public database. Survival analysis showed that mCRC patients with N-terminus side APC mutations had longer overall survival than C-terminus side. Tumor gene pathway analysis showed that gene mutations in the RTK/RAS, Wnt and transforming growth factor β signaling pathways of the C-terminal group were significantly higher than those of the N-terminal group (p < 0.05). Additionally, KRAS, AMER1, TGFBR2, and ARID1A driver mutations were more common in patients with C-terminal side APC mutations. @*Conclusion@#APC specific mutations have potential function as mCRC prognostic biomarkers. There are obvious differences in the gene mutation patterns between the C-terminus and N-terminus APC mutations group, which may have certain guiding significance for the subsequent precise treatment of mCRC.

Amelioration of Cognitive Dysfunction in Diabetic Rats by Jianpi Qinghua Prescription / 中国实验方剂学杂志

ObjectiveTo explore the amelioration of cognitive dysfunction in diabetes mellitus （DM） by Jianpi Qinghua prescription （JPQH） based on type 2 diabetes （T2DM） model rats. MethodFifty healthy male Wistar rats of SPF grade were randomly divided into control group （n=10） and experimental group （n=40）. The rats in the control group were fed conventionally， while those in the experimental group were fed on a high-sugar， high-fat diet for six weeks and administered with streptozotocin （STZ） for the induction of the DM model. The model rats were randomly divided into model group， sitagliptin group （1.2 g·L-1）， pioglitazone group （0.8 g·L-1）， and JPQH group （1.3 g·mL-1）， with 10 rats in each group. After six weeks of drug intervention， the changes in body weight， blood glucose， and other related indexes of each group were recorded. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the peripheral blood and brain. The Morris water maze test was used to evaluate the cognitive function in rats. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the hippocampal CA region. The amyloid β-protein 40 （Aβ40） level was detected by immunohistochemistry. The protein expression of t-tau and p-tau in hippocampal neurons of rats was detected by Western blot. ResultCompared with blank group， the body weight of model group was significantly decreased （P<0.05）， blood glucose level was significantly increased （P<0.01）， inflammatory cytokines TNF-α and IL-1β were increased （P<0.05）， learning and spatial ability were significantly decreased （P<0.01）， the arrangement of hippocampal cells was loose and disordered， and the intercellular space was significantly increased. The number of cells decreased significantly， and the expression of Aβ40 increased significantly. and increased t-tau and p-tau protein content in the hippocampus （P<0.01）. Compared with model group， the JPQH group showed reduced blood glucose （P<0.01）， decreased TNF-α and IL-1β levels in the peripheral blood and cerebrospinal fluid （P<0.05）， a downward trend of IL-6 without a statistical difference， improved learning and spatial memory ability （P<0.01）， densely arranged cells in the hippocampal CA1 area， increased cell number， reduced Aβ40 expression， and decreased p-tau protein expression （P<0.05）. ConclusionJPQH can prevent cognitive dysfunction in DM by reducing inflammatory factor levels， decreasing neurotoxicity caused by Aβ40 deposition， and inhibiting hyperphosphorylation of tau protein in DM rats.

Multi －database analysis and experimental study on the expression of HNF4A in gastric cancer / 安徽医科大学学报

Objective@#To investigate the expression，prognosis and biological role of hepatocyte nuclear factor 4A (HNF4A) in gastric cancer，and to study its effect on the proliferation of gastric cancer cells．@*Methods@#Tumor Immune Estimation Resource 2. 0 (TIMER2. 0) and Gene Expression Profiling Interactive Analysis ( GEPIA2) databases were used to analyze the relative expression levels of HNF4A in gastric cancer and normal tissue，KM Plotter was used to analyze the correlation between the expression level of HNF4A and the survival rate of gastric cancer patients，TISIDB database and R language (4. 1. 2) were used to analyze whether HNF4A was involved in the immune regulation process of gastric cancer．cBioPortal database was used to analyze the mutations of HNF4A in gastric cancer，GSEA 4. 2 was used to analyze the functional enrichment of HNF4A，and LinkedOmics database was used to predict the genes that might be regulated by HNF4A．The relative expression of HNF4A in gastric cancer and adjacent tissues was detected by qRT-PCR , Western blot and immunohistochemistry (IHC) ．The proliferation and cell cycle of gastric cancer cells were analyzed by CCK-8，EdU，colony forming assay and flow cytometry. @*Results @#The expression of HNF4A increased in gastric cancer tissues (P ＜0. 05) ，and the overall survival rate of gastric cancer patients with high HNF4A expression was worse (P＜0. 001) ．HNF4A was mainly missense mutated in gastric cancer．Immune cell infiltration showed that HNF4A was associated with B lymphocytes，CD8 + T cells， neutrophils，macrophages and dendritic cells ( all P ＜0. 001) ． HNF4A was also associated with tumor mutation burden (r = 0. 28，P＜0. 0001) and microsatellite instability (r = 0. 13，P＜0. 01) ．After knockdown of HNF4A， cell proliferation ability was significantly inhibited ，and cell cycle was arrested at G0 / G1 phase．@*Conclusion@#HNF4A expression significantly increased in gastric cancer tissues，which is associated with poor prognosis ，and may also be involved in immune regulation． Knockdown of HNF4A can inhibit the proliferation of gastric cancer cells.

Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial.@*METHODS@#A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored.@*RESULTS@#Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000).@*CONCLUSION@#SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).

Automatic synthesis and in vivo imaging of Al 18F-NOTA-FAPI-04 / 中华核医学与分子影像杂志

Objective:To automatically synthesize Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors. Methods:Al 18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al 18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice ( n=3) and 4T1 breast cancer models ( n=3) to determine its biodistribution. Then Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old). Results:The synthesis time of Al 18F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al 18F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al 18F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al 18F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by 18F-FDG. Conclusions:Al 18F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al 18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.

The influence of Jianpi Qinghua formula on skeletal muscle protein accompanied by insulin resistance by increasing FoxO1 phosphorylation / 国际中医中药杂志

Objective:Based on the degradation of skeletal muscle protein MuRF mediated by pFoxO1 when insulin resistance occurs, this paper explores the content change of skeletal muscle protein and the effect of Jianpi Qinghua formula when insulin resistance occurs.Methods:C57 mice were fed with high-fat food and made as the model of obesity accompanied by insulin resistance. Then they were divided into model group, Jianpi Qinghua formula group and metformin group according to random number table method with 10 mice in each group. Jianpi Qinghua formula group was orally administered with water decoction 20.961 g/kg, and the metformin group was orally administered with metformin suspension 18.498 g/kg, once a day for 12 consecutive weeks. Intraperitoneal Glucose Tolerance Tests (IPGTT) was used after the model was established and intervened respectively. The relative protein content of pFoxO1, FoxO1, MuRF, MyoD and myosin were detected by Western blot method, and the localization of MyoD and myosin was detected by immuno-histochemistry.Results:Compared with the model group, the blood glucose of IPGTT at 0 min, 60 min and 120 min of both Jianpi Qinghua formula group and Metformin group decreased ( P<0.05). Compared with model group, the ratio of pFoxO1/FoxO1 protein expression level (0.27±0.07, 0.24±0.14 vs. 0.05±0.03) of both Jianpi Qinghua formula group and Metformin group increased ( P<0.05), and the relative expression of MuRF protein (1.22±0.42, 1.15±0.32 vs. 3.21±0.35) of both Jianpi Qinghua formula group and Metformin group decreased ( P<0.05). The relative protein expression of MyoD (1.42±0.45 vs. 0.40±0.11) and myosin (0.80±0.11 vs. 0.51±0.08) relative protein expression of Jianpi Qinghua formula group was significantly higher than that of model group ( P<0.05). Immunohistochemical staining showed that MyoD (5.06±1.72 vs.2.28±0.83) and myosin (60.28±7.47 vs. 39.77±3.34) of Jianpi Qinghua formula group significantly increased compared with model group ( P<0.05). Conclusion:Jianpi Qinghua formula could effectively increase the content of skeletal muscle protein, enhancing the phosphorylation of FoxO1 in skeletal muscle and the inhibition of MuRF degradation pathway.

Effect of transitional nursing combined with resistance breathing training on elderly obese obstructive sleep apnea-hypopnea syndrome / 中国实用护理杂志

Objective:To analyze the effect of transitional care model (TCM) mode combined with resistance breathing training on hypoxic reactivity of respiratory center in elderly obese obstructive sleep apnea-hypopnea syndrome(OSAHS).Methods:Totally 78 patients with OSAHS who met the criteria were selected from the geriatric department of Nanjing Drum Tower Hospital from January 2018 to December 2020 and divided into observation group and control group by random digits table method, with 39 cases in each group; the control group was intervened by basic nursing combined with resistance breathing training mode, and the observation group was intervened by TCM mode on the basis of the control group. Before nursing and 1 month after discharge, Pittsburgh Sleep Quality Index (PSQI), Short-Form 36-item Health Survey (SF-36), Montreal Cognitive Assessment (MoCA) were used to evaluate the sleep quality, quality of life and cognitive function of the patients. Besides, FVC, FEV 1, FEV 1/FVC were also tested before nursing and 1 month after discharge. Results:One month after discharge, the daytime dysfunction, use of sleep drugs, habitual sleep efficiency, subjective sleep quality, sleep disorder, sleep latency, sleep duration and total score of PSQI in the observation group were significantly lower than those in the control group (the control group: 2.27 ± 0.34, 2.03 ± 0.31, 2.09 ± 0.23, 1.85 ± 0.28, 2.11 ± 0.28, 1.40 ± 0.24, 2.12 ± 0.41, 13.87 ± 0.56; the observation group: 1.63 ± 0.33, 1.22 ± 0.29, 1.63 ± 0.29, 1.12 ± 0.31, 1.35 ± 0.34, 1.09 ± 0.28, 1.74 ± 0.26, 9.78 ± 0.59) ( t values were 4.91-31.61, all P<0.01). One month after discharge, the scores of mental health, physical pain, physiological function, physiological function, emotional function, life vitality, social function and overall health of SF-36 in the observation group were significantly higher than those in the control group (the control group: 62.83 ± 6.31, 68.94 ± 5.91, 61.99 ± 5.98, 64.85 ± 6.13, 43.28 ± 5.74, 64.85 ± 6.12, 61.21 ± 5.74, 62.31 ± 6.85; the observation group: 69.81 ± 5.74, 76.12 ± 6.02, 70.84 ± 6.08, 71.74 ± 5.99, 50.93 ± 6.12, 70.52 ± 5.94, 69.89 ± 5.53, 68.41 ± 4.99)( t values were 4.18-7.77, all P<0.01). One month after discharge, the scores of visual space and executive function, attention, language, delayed recall, orientation, abstraction and total score of MoCA in the observation group were significantly higher than those in the control group (the control group: 4.48 ± 0.37, 5.23 ± 0.29, 2.43 ± 0.27, 3.37 ± 0.31, 5.01 ± 0.33, 5.27 ± 0.26, 25.79 ± 1.17; the observation group:4.95 ± 0.31, 5.68 ± 0.27, 2.67 ± 0.24, 3.98 ± 0.19, 5.47 ± 0.28, 5.64 ± 0.23, 28.39 ± 1.09)( t values were 4.17-10.51, all P<0.01). One month after discharge, the levels of FVC, FEV 1 and FEV 1/FVC in the observation group were significantly higher than those in the control group, the control group: (2.59 ± 0.18) L, (1.60 ± 0.14) L, (61.78 ± 4.01)%; the observation group: (2.89 ± 0.19) L, (1.99 ± 0.17) L, (68.86 ± 3.99)% ( t = 7.21, 11.14, 7.87, all P<0.05). Conclusions:TCM combined with resistance breathing training can effectively improve the hypoxic response of respiratory center in elderly obese patients with OSAHS.

Prognostic analysis of different comprehensive treatment models for locally advanced esophageal squamous cell carcinoma based on propensity score matching / 中华外科杂志

Objective: To compare the effects of preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the long-term survival of patients with radical resection for esophageal squamous cell carcinoma. Methods: Totally 1 082 patients with stage T3-4aN0-3M0 thoracic esophageal squamous cell carcinoma were recruited in this study who underwent radical resection at Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University from January 2005 to January 2015. There were 798 males and 284 females, with a median age of 61 years (range: 37 to 86 years). There were 138 patients undergoing preoperative neoadjuvant chemotherapy, 392 patients postoperative adjuvant chemotherapy, and 552 patients surgery alone. The neoadjuvant chemotherapy group was used as the benchmark group to match the propensity score with the adjuvant chemotherapy group and the surgery-only group respectively at a ratio of 1∶3. A total of 7 covariates including tumor location, number of positive lymph nodes, tumor invasion depth, tumor differentiation degree, surgical procedure, vascular tumor thrombus and nerve invasion were included, and the caliper value was taken as 0.1. After matching, a total of 699 patients were included for the analysis, including 128 patients in the neoadjuvant chemotherapy group, 267 patients in the adjuvant chemotherapy group, and 304 patients in the surgery alone group. The Kaplan-Meier method was used to generate the survival curves which was tested by the Log-rank method for survival analysis. Results: After matching analysis, the 5-year overall survival rate was 41.5% in the neoadjuvant chemotherapy group with a median overall survival time of 43 months (95%CI: 27 to 59 months), 57.6% in the adjuvant chemotherapy group with a median overall survival time unreached, and 24.9% in the surgery alone group with a median overall survival time of 28 months (95%CI: 25 to 31 months) (χ²=60.475, P<0.01). For overall survival after matching, the adjuvant chemotherapy group was better than the neoadjuvant chemotherapy group (χ²=11.384, P=0.001), the neoadjuvant chemotherapy group was better than the surgery alone group (χ²=8.654, P=0.003), and the adjuvant chemotherapy group was better than surgery alone group (χ²=60.234, P<0.01). Conclusion: Both preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy can improve the long-term survival of patients with locally advanced esophageal squamous cell carcinoma undergoing radical resection, and the improvement effect of postoperative adjuvant chemotherapy is more obvious.