Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly (version 2023) / 中华创伤杂志

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Application of bedside ultrasound in the evaluation of volume responsiveness in patients with septic shock / 中国医师杂志

Objective:To evaluate the value of bedside ultrasound in evaluating volume responsiveness of patients with septic shock.Methods:A total of 102 patients with septic shock admitted to ICU of the First Affiliated Hospital of Hebei North University from April 2018 to February 2021 were selected. Patients were divided into response group and non-response group according to the value of stroke volume increase (ΔSV) after volume loading test (VE), and the hemodynamic parameters before and after VE were compared between the two groups. Pearson correlation was used to analyze the relationship between ΔSV and hemodynamic indexes. Receiver operating characteristic (ROC) curve was drawn to analyze the sensitivity and specificity of each hemodynamic index in evaluating volumetric reactivity in patients with septic shock.Results:Of the 102 patients, 54 responded and 48 did not. Before VE, the distensibility index of inferior vena cava (ΔIVC 1), espiratory variability index of inferior vena cava (ΔIVC 2), respiratory variability of aortic peak velocity (ΔVpeak AO), brachial artery maximum velocity variability (ΔVpeak BA) and respiratory rate of peak flow velocity of femoral artery (ΔVpeak CFA) in response group were higher than those in non-response group (all P<0.05), but there was no statistical significance in heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP) between 2 groups (all P>0.05). After VE, the HR, ΔIVC 1, ΔIVC 2, ΔVpeak AO, ΔVpeak BA and ΔVpeak CFA in response group were significantly decreased, while MAP and CVP were significantly increased (all P<0.05). The CVP was significantly decreased in the non-response group ( P<0.05), while other indexes were not significantly changed. Before VE, the ΔIVC 1, ΔIVC 2, ΔVpeak AO, ΔVpeak BA and ΔVpeak CFA were positively correlated with ΔSV ( r=0.589, 0.647, 0.697, 0.621, 0.766; all P<0.05). There was no correlation between CVP and ΔSV ( r=-0.345, P>0.05). Before VE, the area under the curve of ΔIVC 1, ΔIVC 2, ΔVpeak AO, ΔVpeak BA and ΔVpeak CFA were all >0.7, indicating high sensitivity and specificity. Conclusions:Bedside ultrasound monitoring ΔIVC, ΔVpeak AO, ΔVpeak BA and ΔVpeak CFA can better evaluate the volume response of patients with septic shock, and can provide a reference basis for clinical fluid resuscitation treatment.

Construction and evaluation of a prognostic model for severe acute pancreatitis based on CT scores and inflammatory factors / 中华危重病急救医学

Objective:To construct a prognostic model for severe acute pancreatitis (SAP) based on CT scores and inflammatory factors, and to evaluate its efficacy.Methods:128 patients with SAP diagnosed admitted to the First Hospital Affiliated to Hebei North College from March 2019 to December 2021 were enrolled and given Ulinastatin combined with continuous blood purification therapy. The levels of C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-8), tumor necrosis factor-α (TNF-α), and D-dimer were measured before and on the third day of treatment. An abdominal CT was performed on the third day of treatment to assess the modified CT severity index (MCTSI) and extra-pancreatic inflammatory CT score (EPIC). Patients were divided into the survival group ( n = 94) and the death group ( n = 34) according to the 28-day survival prognosis after admission. The risk factors for the SAP prognosis were analyzed using Logistic regression, which was then used to build nomogram regression models. The value of the model was evaluated using the concordance index (C-index), calibration curves and decision curve analysis (DCA). Results:Before treatment, the levels of CRP, PCT, IL-6, IL-8 and D-dimer in the death group were higher than those in the survival group. After treatment, the levels of IL-6, IL-8 and TNF-α in the death group were higher than those in the survival group. MCTSI and EPIC scores in the survival group were lower than those in the death group. Logistic regression analysis shows that, pre-treatment CRP > 140.70 mg/L, D-dimer > 2.00 mg/L, and post-treatment IL-6 > 31.28 ng/L, IL-8 > 31.04 ng/L, TNF-α > 31.04 ng/L, and MCTSI > 8 points were all independent risk factors for SAP prognosis [odds ratios ( OR) and 95% confidence intervals (95% CI) were 8.939 (1.792-44.575), 6.369 (1.368-29.640), 8.546 (1.664-43.896), 5.239 (1.108-24.769), 4.808 (1.126-20.525), 18.569 (3.931-87.725), all P < 0.05]. Model 1 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α) had a lower C-index than that model 2 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI; 0.988 vs. 0.995). The mean absolute error (MAE) and mean square error (MSE) of model 1 (0.034, 0.003) were higher than those of model 2 (0.017, 0.001). When the threshold probability was in the range of 0-0.66 or 0.72-1.00, the net benefit of model 1 was lower than that of model 2. When the threshold probability was in the range of 0.66-0.72, the net benefit of model 1 was higher than that of model 2. In addition, model 2 had a higher C-index than acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) and bedside index of acute pancreatitis severity (BISAP, 0.995 vs. 0.833, 0.751). Model 2 had a lower MAE (0.017) and MSE (0.001) than APACHEⅡ (0.041, 0.002). Model 2 had a lower MAE than BISAP (0.025). Model 2 had a higher net benefit than both APACHEⅡ and BISAP. Conclusion:The prognostic assessment model of SAP consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI has high discrimination, precision and clinical application value, and is superior to APACHEⅡ and BISAP.

Clinical effect of minimally invasive catheterization based on computer 3D-Slicer software system in the treatment of hypertensive intracerebral hemorrhage / 中国医师进修杂志

Objective:To investigate the clinical effect of minimally invasive catheterization based on computer 3D-Slicer software system in the treatment of hypertensive intracerebral hemorrhage (HICH).Methods:Three hundred and fifty patients with HICH treated in People′s Hospital of Lanling County in Shandongfrom June 2019 to June 2020 were selected as the research object. According to the operation method, they were divided into 3D-Slicer group (175 cases) and CT group (175 cases). They were treated with 3D-Slicer software-assisted minimally invasive catheterization and minimally invasive soft-channel drainage under CT localization, respectively. The general conditions of the surgery, hematoma clearance rate and laboratory indexes, oxidative stress index and prognosis were compared between the two groups.Results:The intraoperative blood loss, the hospitalizationtimein the 3D-Slicer group were lower than those in the CT group: (81.42 ± 12.33) ml vs. (101.54 ± 11.71) ml, (15.67 ± 3.71) d vs. (17.22 ± 3.52) d; the success rate of one-time successful puncture to preset position in the 3D-Slicer group was higher than that in the CT group: 100.00%(175/175) vs. 81.14%(142/175), there were statistical differences ( χ 2 = 34.26, P<0.05). The hematoma clearance rate after the surgery for 1, 3 and 7d in the 3D-Slicer group were higher than those in the CT group:(87.93 ± 8.54)% vs. (66.43 ± 7.99)%, (92.48 ± 10.31)% vs. (89.52 ± 11.74)%, (96.37 ± 10.22)% vs. (94.30 ± 9.25)%, there were statistical differences( P<0.05). After the surgery for 7 d, the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in the 3D-Slicer group were higher than those in the CT group: (121.36 ± 10.59)U/L vs. (109.14 ± 9.05) U/L, (92.80 ± 8.63) μg/L vs. (81.45 ± 9.11) μg/L, (24.64 ± 5.43) U/L vs. (20.84 ± 3.47) U/L; while the level of malondialdehyde (MDA) was lower than that in the CT group: (4.42 ± 0.57)μmol/L vs. (5.19 ± 0.51) μmol/L, there were statistical differences ( P<0.05). After the surgery for 3 months, the rate of favorable prognosis in the 3D-Slicer group was higher than that in the CT group 73.71%(129/175) vs. 62.29%(199/175), there was statistical difference ( χ2 = 5.25, P<0.05). Conclusions:Minimally invasive catheterization based on 3D-Slicer software system in the treatment of HICH can not only improve the clinical efficacy, but also shorten the hospitalization time, reduce intraoperative blood loss, and improve the prognosis.

Clinical efficacy of radical resection of pancreatic cancer after neoadjuvant conversion therapy / 中华消化外科杂志

Objective:To investigate the clinical efficacy of radical resection of pancreatic cancer after neoadjuvant conversion therapy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 23 patients who underwent radical resection of pancreatic cancer after neoadjuvant conversion therapy in Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from January 2019 to May 2022 were collected. There were 17 males and 6 females, aged 58(range, 33-73)years. After neoadjuvant conversion therapy, the three-dimensional (3D) visualization was used to evaluate and classify tumor vascular invasion, and surgical plan was planned and implemented. Observation indicators: (1) situations of neoadjuvant conversion therapy; (2) surgical situations; (3) postoperative histopathological examination; (4) postoperative recovery; (5) follow-up. Measurement data with normal distribution were represen-ted as Mean± SD, and measurement data with skewed distribution were represented as M(range) or M( Q1, Q3). Count data were described as absolute numbers. Results:(1) Situations of neoadjuvant conversion therapy. All 23 patients received the AG combination chemotherapy (albumin-paclitaxel+gemcitabine), including 14 patients combined with stereotactic body radiation therapy. Of the 23 patients, 22 cases achieved partial response, and 1 case showed stable disease. The CA19-9 of the 23 patients was 85.06(29.74,634.5)U/mL and 13.96(9.74,25.02)U/mL before and after neoadjuvant conversion therapy, respectively. (2) Surgical situations. According to the results of preoperative 3D visualization of tumor vascular invasion, 7 of the 23 patients were evaluated as arterial invasion, 8 cases were evaluated as venous invasion, 5 cases were evaluated as arterial and venous invasion, and there were 3 cases showing negative of vascular invasion. Of the 23 patients, 12 cases underwent pancreaticoduodenectomy, 4 cases underwent radical antegrade modular pancreatosplenectomy, 7 cases underwent total pancreaticoduodenectomy. For vascular reconstruction, there were 10 patients without vascular reconstruction, and there were 13 patients undergoing artificial vascular vein reconstruction. The operation time and volume of intraoperative blood loss of the 23 patients was (524±171)minutes and 1 000(400,1 600)mL, respectively. (3) Postoperative histopathological exami-nation. Results of postoperative histopathological examination in 23 patients showed that there were 2 cases with moderate-well differentiated tumor, 10 cases with moderate differentiated tumor, 7 cases with moderate-poorly differentiated tumor, 2 cases with poorly differentiated tumor, and 2 cases negative of tumor. The number of lymph node dissected in 23 patients was 16±7. There were 5 cases with lymph node metastasis and 18 cases without lymph node metastasis. There were 17 cases with nerve invasion and 6 cases without nerve invasion. All 23 patients were negative of vascular invasion. Of the 23 patients, there were 21 cases with R 0 resection and 2 cases with R 1 resection. For pathological TNM staging, there were 2 cases with 0 stage, 13 cases with Ⅰ stage, 7 cases with Ⅱ stage, and 1 case with Ⅳ stage. For postoperative pathological scoring, there were 2 cases achieved 0 point (complete pathological remission), 16 cases achieved 2 points (partial remission), and 5 cases achieved 3 points (no significant effect). (4) Postoperative recovery. The postoperative duration of hospital stay of 23 patients was 19(14,31)days. There were 17 of 23 patients underwent postoperative complications, including 11 cases with Clavien-Dindo Ⅱ stage complications, 3 cases with Clavien-Dindo Ⅲa stage complications, 1 case with Clavien-Dindo Ⅲb stage complication, 1 case with Clavien-Dindo Ⅳ stage complication, and 1 case with Clavien-Dindo Ⅴ stage complica-tion. (5) Follow-up. There were 22 patients underwent follow-up, with follow-up time as 12(9,23)months. There were 9 patients underwent postoperative recurrence and metastasis, with recurrence and metastasis time as 7.8(range, 6.0-12.0)months. During the follow-up, 15 of the 22 patients survived. Conclusion:Radical resection of pancreatic cancer after neoadjuvant conversion therapy is feasible.

Surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multi-disciplinary diagnosis and treatment / 中华消化外科杂志

Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.

First-in-class small molecule drugs in 2022 / 药学学报

2022 is the third year of the global COVID-19 pandemic, and its troubles on new drug discovery are gradually apparent. 37 new drugs were approved by the FDA's Center for Drug Evaluation and Research (CDER) last year, down from the peak of 50 new drug approvals in 2021. Notably, first-in-class drugs still occupy a dominant position this year, with a total of 21 drugs. Among them, 7 are first-in-class small molecule drugs. Although the total number of new drug approvals in 2022 sharply decreased, some first-in-class small molecule drugs were regarded as significant, including mitapivat, the first oral activator targeting the pyruvate kinase (PK); mavacamten, the first selective allosteric inhibitor targeting the myocardial β myosin ATPase; deucravacitinib, the first deuterated allosteric inhibitor targeting the tyrosine kinase 2 (TYK2); and lenacapavir, the first long-acting inhibitor targeting the HIV capsid. Generally, the research of first-in-class drugs needs to focus on difficult clinical problems and can treat some specific diseases through novel targets and biological mechanisms. There are tremendous challenges in the research processes of new drugs, including biological mechanism research, target selection, molecular screening, lead compound identification and druggability optimization. Therefore, the success of first-in-class drugs development has prominent guidance significance for new drug discovery. This review briefly describes the discovery background, research and development process and therapeutic application of 3 first-in-class small molecule drugs to provide research ideas and methods for more first-in-class drugs.

Therapeutic effects of paeoniflorin on irritable bowel syndrome in rats

Background@#Irritable bowel syndrome (IBS) is a functional bowel disorder (FBD). @*Objectives@#To assess the therapeutic effects of paeoniflorin (PF) on IBS in rats.Method: Sixty male Sprague–Dawley rats were randomly divided into normal, model, positive drug, low-dose PF, medium-dose PF and high-dose PF groups (n = 10). After gavage for 2 consecutive weeks, the effect of PF on abdominal pain symptoms was assessed based on the abdominal withdrawal reflex (AWR) score, fecal water content and pathological changes in colon tissues. D-lactate, interleukin-1β (IL-1β), transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay, and phosphorylated nuclear factor kappa B (p-NF-κB) p65 was detected by Western blotting. The abundance and diversity changes of intestinal flora were explored using 16S ribosomal RNA sequencing.Result: In PF groups, the mucosal morphology of colon tissues was intact, and the glands were arranged neatly and structured clearly, without obvious inflammatory cell infiltration.Compared with the model group, PF groups had significantly elevated pain threshold, and mRNA and protein levels of zonula occludens-1 (ZO-1) and occludin, decreased AWR score at 20 mmHg pressure, fecal water content, mRNA levels of IL-1β, TGF-β, and TNF-α, protein level of p-NF-κB p65 and level of serum D-lactate, and reduced levels of serum IL-1β, TGF-β, and TNF-α (p < 0.05, p < 0.01). PF groups had higher abundance of Lactobacillus, Akkermansia, Alistipes, and Bacteroides, but lower abundance of Desulfovibrio, Parasutterella, and Enterococcus than those of the model group. @*Conclusions@#PF exerts therapeutic effects on IBS in rats probably by regulating the intestinal flora, and then up-regulating the expressions of ZO-1 and occludin in colon tissue while down-regulating the levels of IL-1β, TGF-β, TNF-α, D-lactate and p-NF-κB p65.

Correlation of OCTN2 with the chemosensitivity of prostate cancer cells to oxaliplatin / 中国药房

OBJECTIVE To study the correlation of novel organic cation transporter 2 （OCTN2） with the chemosensitivity of prostate cancer cells to oxaliplatin. METHODS Tumor samples of patients receiving radical prostatectomy were collected， and OCTN2 protein was detected with immunohistochemistry； the primary cells of the specimen were cultivated to obtain prostate cancer cell line. Inductively coupled plasma mass spectrometry was used to detect the uptake of low concentration （0.1 μmol/L） of oxaliplatin by cancer cells. Real-time PCR and Western blot were used to detect the mRNA and protein expressions of OCTN2 in cancer cells； the prostate cancer cells with the highest and lowest expression of OCTN2 protein were selected， and IC50 of oxaliplatin to prostate cancer cells was analyzed by ATP-TCA method. The inhibitory rate of plasma peak concentration of oxaliplatin （50 μmol/L） to prostate cancer cells was detected by MTT assay. Spearman method was used to analyze the relationship of the uptake of oxaliplatin by prostate cancer cells with inhibitory rate of oxaliplatin to prostate cancer cells and 505916443@qq.com mRNA expressions of OCTN2. RESULTS OCTN2 was located on the membrane of cancer cells， and the uptake of zjdtztougao@163.com oxaliplatin by cancer cells was 0.283±0.264 （n＝12）mRNA and protein expression of OCTN2 varied significantly among different cancer cells. The sensitivity of cancer cells with high expression of OCTN2 to oxaliplatin （IC50 of 4.61 μmol/L） was higher than that of cancer cells with lower expression of OCTN2 （IC50 of 26.23 μmol/L）. The inhibitory rate of oxaliplatin to cancer cells was （25.4±10.8）% （n＝12）. There was a correlation between the uptake of oxaliplatin by prostate cancer cells and the inhibition rate of oxaliplatin to prostate cancer cells and mRNA expression of OCTN2 （P＜0.05）. CONCLUSIONS High-expressed OCTN2 may promote the uptake of oxaliplatin by prostate cancer cells， and its expression can serve as a reference for predicting the sensitivity of prostate cancer cells to oxaliplatin chemotherapy.

Clinical characteristics of dry eye in patients with type 2 diabetic peripheral neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical features of dry eye in patients with type 2 diabetes mellitus complicated with peripheral neuropathy.METHOD: Prospective cohort study. A total of 192 patients with type 2 diabetes were enrolled in the Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from July 2021 to March 2022. The right eyes of all patients were selected as the observation eye, among which 122 patients were diagnosed with diabetic peripheral neuropathy(DPN)and 70 patients were diagnosed with non-diabetic peripheral neuropathy(NDPN). The score of ocular surface disease index(OSDI), tear meniscus height, tear meniscus width, corneal epithelial thickness, corneal endothelial cell density, tear secretion test(Schirmer Ⅰ test, SⅠt), corneal sensitivity, meibomian gland function status score, tear film breakup time(BUT), corneal fluorescein sodium staining score and Toronto clinical scoring system(TCSS)score were compared between two groups. The correlation between OSDI score and TCSS score in type 2 diabetes patients was analyzed as well.RESULTS: The morbidity of dry eye in the DPN group(55 eyes, 45.1%)was significantly higher than that of NDPN group(20 eyes, 28.6%; χ2=5.094, P=0.024), BUT and corneal sensitivity score of DPN were lower than NDPN group(P&#x003C;0.001), meanwhile, corneal staining score and meibomian gland function score were higher than NDPN group(P&#x003C;0.001). OSDI scores of all subjects were negatively correlated with TCSS scores(rs=-0.233, P=0.002), and OSDI scores of DPN group were negatively correlated with TCSS scores(rs=-0.511, P&#x003C;0.001), but there was no significant correlation between the two scores of NDPN patients(rs=0.007, P=0.957).CONCLUSIONS: DPN patients are more likely to develop dry eye than NDPN patients. OSDI score is not an accurate evaluation index for type 2 diabetes patients, especially for DPN patients.

Comparative study on the treatment of rhegmatogenous retinal detachment between foldable capsular body and scleral buckling / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the effectiveness and complications of treating rhegmatogenous retinal detachment(RRD)with foldable capsule body(FCB)and scleral buckling(SB).METHODS: The clinical data of 81 patients(82 eyes)with RRD who underwent surgery at our hospital from March 2019 to April 2022 were retrospectively analyzed. The differences in retinal reattachment rate, best-corrected visual acuity, the absorption of subretinal fluid, postoperative discomfort and incidence of complications between the two treatments were compared.RESULTS: The retinal reattachment rate was 96% in the FCB group and 92% in the SB group, with no significant difference between the two groups(P&#x003E;0.05). The best corrected visual acuity of the affected macular eyes was different in the both groups(P&#x003C;0.01). Both groups effectively promoted the absorption of subretinal fluid. The operation time of FCB group was 16.50(12.75, 25.00)min, while it was 38.00(36.25, 41.75)min in the SB group(P&#x003C;0.001). Patients in the FCB group also had significantly lower eyelid swelling and pain symptoms than those in the SB group(P&#x003C;0.001). The visual analogue scale(VAS)score at 1d after operation was 1.00(0.00, 2.00)in the FCB group and 3.00(2.00, 3.00)in the SB group(P&#x003C;0.001).CONCLUSION: FCB is a safe and effective surgical method to treat RRD that can alleviate patient's pain. Furthermore, FCB has a significantly shorter operation time and milder postoperative adverse reactions than SB.

Mechanism of Guishao Yunpi Decoction in Prevention and Treatment of Mammary Gland Hyperplasia Based on PTEN/PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveStudy on the mechanism of Guishao Yunpi decoction in preventing and treating breast hyperplasia based on phosphatase and tensin homolog （PTEN）/ phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodSeventy SPF-grade SD rats were randomly assigned into blank group （n=15） and modeling group （n=55）. The mammary gland hyperplasia model of liver stagnation and spleen deficiency was established by the comprehensive modeling method （hunger and satiety abnormality + tail stimulation + estradiol benzoate + progesterone）， and then 5 rats were randomly selected for model verification. The modeled rats were then randomly assigned into five groups： model group， positive control （4 mg·kg-1·d-1 tamoxifen） group， and high-， medium-， and low-dose （17.2， 8.6， 4.3 g·kg-1·d-1， respectively） Guishao Yunpi decoction groups， with 10 rats in each group. The rats in the blank group and model group were given 10 mL·kg-1·d-1 distilled water， and those in other groups were orally administrated with corresponding drugs. After 30 days of treatment， the general living conditions of rats were observed， and the thickness of breast tissue was measured by an ultrasonic diagnostic instrument. The open field test was carried out for behavioral evaluation. The levels of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X （Bax） in the breast tissue were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein levels of PTEN， PI3K， and Akt in the breast tissue were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with those in the blank group， the rats in the model group were irritable， curled up in clusters， and showed positive behavior in the open field test. The modeling led to nipple swelling and increased the breast thickness （P<0.05）. Moreover， the modeling elevated the level of Bcl-2 and lowered that of Bax in the breast tissue （P<0.05）， down-regulated the mRNA and protein levels of PTEN， and up-regulated the mRNA and protein levels of PI3K and Akt （P<0.05）. Compared with the model group， drug administration relieved the general survival state， the degree of nipple swelling， and the positive behavior in the open field test and reduced the breast thickness （P<0.05）. In addition， drug administration reduced the level of Bcl-2 and increased that of Bax in the breast tissue （P<0.05）， up-regulated the mRNA and protein levels of PTEN， and down-regulated the mRNA and protein levels of PI3K and Akt （P<0.05）. ConclusionGuishao Yunpi decoction can improve the general living conditions and alleviate the mammary gland hyperplasia of rats with the syndrome of liver depression and spleen deficiency， which may be realized by the regulation of the PTEN/PI3K/Akt pathway.

A metabolic intervention strategy to break evolutionary adaptability of tumor for reinforced immunotherapy

The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8+ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.

Clinical efficacy analysis of functional rhinoplasty assisted by nasal endoscopy / 中华耳鼻咽喉头颈外科杂志

Objective: To analyse the clinical effect of endoscopy-assisted functional rhinoplasty. Methods: Twenty-one patients with congenital or traumatic deviated nose with nasal obstruction admitted to Qilu Hospital (Qingdao) from January 2018 to December 2021, including 8 males and 13 females, aged 22 to 46 years, were retrospectively analysed. Endoscopy-assisted functional rhinoplasty was performed in all patients. Deviated nasal septum was corrected, nasal septum cartilage graft was prepared through open approach assisted by endoscopy, the nasal frame structure was adjusted with the endoscopy-assisted rhinoplasty combined with middle and inferior turbinoplasty, and the patient's nasal ventilation function and external nose cosmetology were restored. Visual Analogue Scale (VAS), Nasal Obstruction Symptom Evaluation (NOSE), nasal acoustic reflex and nasal resistance were examined preoperatively and 6 months postoperatively. The minimum cross-sectional area of the first two nasal cavities (MCA) MCA1 and MCA2 and their distance between nostrils to the minimum cross-sectional area (MD) MD1 and MD2 were recorded, and the ratio of both sides (expressed in a/b) was calculated. The nasal volume of 5 cm depth from nostril (NV5) and nasal resistance total (RT) were recorded to evaluate the nasal ventilation function to analyse the clinical effect of functional rhinoplasty assisted by nasal endoscope. SPSS 25.0 software was used for statistical analysis. Results: At 6 months after the operation, for nasal ventilation evaluation, the VAS and NOSE scores of nasal obstruction decreased significantly than those before the operation ((1.81±0.81) points vs (6.71±1.38) points, (4.19±2.06) points vs (12.05±2.67) points, all P<0.05). In the objective indexes, MCA1, MCA2 and NV5 were significantly increased whereas RT, MCA1a/MCA1b, MCA2a/MCA2b, MD1a/MD1b and MD2a/MD2b were significantly decreased compared with those before the operation (all P<0.05). The MD1 and MD2 levels before and after operation had no significant differences (all P>0.05). In the evaluation of external nose morphology, postoperative ROE was significantly increased, and the deviation value of nasal appearance was significantly decreased ((16.19±2.56) points vs (10.24±3.24) points, (1.55±1.16) mm vs (5.63±2.41) mm, all P<0.05). In terms of postoperative patient satisfaction, 19 cases (90.5%) were very satisfied with nasal ventilation function, 2 cases (9.5%) were satisfied with nasal ventilation function; 15 cases (71.4%) were very satisfied with nasal appearance, and 6 cases (28.6%) were satisfied with nasal appearance. Conclusions: Nasal endoscopy-assisted functional rhinoplasty can improve the nasal ventilation function and external nasal morphology at the same time, with good clinical effect and high patient satisfaction.

Analysis of genotypes on 850 newborns with SLC26A4 single-allele mutation and the phenotypes of those with second variant / 中华耳鼻咽喉头颈外科杂志

Objective: To clarify the phenotypes of the newborns with SLC26A4 single-allele mutation in deafness genetic screening and second variant; to analyze the SLC26A4 genotype and hearing phenotype. Methods: 850 newborns born in Beijing from April 2015 to December 2019 were included and there were 468 males and 382 females. They received genetic deafness screening for 9 or 15 variants, with the result of SLC26A4 single-allele mutation. Firstly, three step deafness gene sequencing was adopted in this work, i.e., the first step was "SLC26A4 gene whole exons and splice sites" sequencing; the second step was "SLC26A4 gene promoter, FOXI1 gene and KCNJ10 gene whole exons" sequencing; and the third step was detection for "SLC26A4 gene copy number variation". Secondly, we collected the results of newborn hearing screening for all patients with the second mutation found in the three step test, and conducted audiological examinations, such as acoustic immittance, auditory brainstem response and auditory steady state response. Thirdly, for novel/VUS mutations, we searched the international deafness gene database or software, such as DVD, ClinVar and Mutation Taster, to predict the pathogenicity of mutations according to the ACMG guideline. Lastly, we analyzed the relationship between genotype and phenotype of newborns with SLC26A4 single allele mutation. Results: Among 850 cases, the median age of diagnosis was 4 months. In the first step, 850 cases were sequenced. A total of 32 cases (3.76%, 32/850) of a second variants were detected, including 18 cases (2.12%, 18/850) with identified pathogenic variants; 832 cases were sequenced and 8 cases of KCNJ10 gene missense variants were detected among the second step. No missense mutations in the FOXI1 gene and abnormal SLC26A4 gene promoter were detected; the third step sequencing results were all negative. Genotypes and hearing phenotypes included 18 cases combined with the second clear pathogenic variant, 16 cases (16/18) referred newborn hearing screening and 2 cases (2/18) passed in both ears; degree of hearing loss consisted of 18 profound ears (18/36), 13 severe ears (13/36) and 5 moderate ears (5/36); audiogram patterns comprised 17 high frequency drop ears (17/36), 14 flat ears (14/36), 3 undistinguished ears (3/36), and 2 U shaped ears (2/36); 11 cases underwent imaging examination, all of which were bilateral enlarged vestibular aqueduct. As for 22 cases of other genotypes, all passed neonatal hearing screening and the hearing diagnosis was normal, including 9 cases with VUS or possibly novel benign variants, 8 cases with KCNJ10 double gene heterozygous variants, and 5 cases with double heterozygous variants. Conclusions: The probability of individuals with SLC26A4 single-allele variant who merge with a second pathogenic variant is 2.12%, all of which are SNV, which can provide scientific basis for the genetic diagnosis and genetic counseling of SLC26A4 variants. Those who have merged with second pathogenic variant are all diagnosed with sensorineural hearing loss. Patients with KCNJ10 gene mutations do not manifest hearing loss during the infancy, suggesting the need for further follow-up.

Therapeutic Efficacy of Shexiang Baoxin Pill Combined with Exercise in Patients with Heart Failure with Preserved Ejection Fraction: A Single-Center, Double-Blind, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the therapeutic efficacy of Shexiang Baoxin Pill combined with exercise in heart failure patients with preserved ejection fraction (HFpEF).@*METHODS@#Sixty patients with HFpEF were randomly divided into group A (n=20), receiving Shexiang Baoxin Pill combined with home-based exercise training based on conventional drugs for 12 weeks; group B (n=20), receiving conventional drugs combined with home-based exercise training for 12 weeks; and group C (n=20), receiving conventional drug treatment only. Peak oxygen uptake (peakVO2), anaerobic threshold (AT), 6-min walking test (6MWT), Pittsburgh Sleep Quality Index (PSQI), and SF-36 questionnaire (SF-36) results before and after treatment were compared among groups.@*RESULTS@#After the 12-week intervention, patients in group C showed significant declines in peakVO2, AT, 6MWT, PSQI, and SF-36 compared with pre-treatment (P<0.01), while groups A and B both showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 results compared with pre-treatment (P<0.01). Compared with group C, patients in groups A and B showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 (P<0.01). In addition, patients in group A showed more significant improvements in physical function, role-physical, vitality, and mental health scores on the SF-36 questionnaire, and PSQI scores than those in group B (P<0.01).@*CONCLUSIONS@#Exercise training improved exercise tolerance, sleep quality and quality of life (QoL) in patients with HFpEF. Notably, Shexiang Baoxin Pill played an active role in sleep quality and QoL of patients with HFpEF. (The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100054322)).

Ganoderma lucidum Polysaccharides Inhibit Malignant Phenotype of Hepatocellular Carcinoma Cells by Regulating PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Ganoderma lucidum polysaccharides （GLP） on the proliferation， migration， cycle， and apoptosis of hepatocellular carcinoma SK­HEP­1 and Huh­7 cells and to explore the underlying mechanism. MethodSK-HEP-1 and Huh-7 cells were classified into the blank group and low-， medium-， and high-dose GLP groups （3.5， 7， 14 g·L-1）. The proliferation of the cells was examined by cell counting kit-8 （CCK­8） assay， and the migration by scratch assay. Cell cycle was measured by flow cytometry and apoptosis was detected based on Hoechst33258 staining. In addition， the expression of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， phosphorylated PI3K （p­PI3K）， and phosphorylated Akt （p­Akt） in the cells was determined by Western blot. ResultCompared with the blank group， the three doses of GLP reduced the proliferation and migration of SK­HEP­1 and Huh­7 cells （P<0.05）， increased the percentage of cells in G1 phase （P<0.05）， and decreased percentage of cells in S and G2 phase （P<0.05）. In addition， the three doses can induce apoptosis of both SK-HEP-1 and Huh-7 cells， particularly the high dose. Moreover， the three doses of GLP lowered the levels of p­PI3K and p­Akt （P<0.05）. ConclusionGLP significantly inhibited the malignant phenotype of SK-HEP-1 and Huh-7 cells through the PI3K/Akt signaling pathway.

PACS and Photoshop assisted isosceles triangle osteotomy and Kirschner wire tension buckle fixation in the treatment of cubitus varus in children / 中国骨伤

OBJECTIVE@#To investigate the clinical efficacy of picture archiving and communication system (PACS) and Photoshop assisted isosceles triangle osteotomy and Kirschner wire fixation with tension band in the treatment of cubitus varus in children.@*METHODS@#The clinic data of 20 children with cubitus varus treated with isosceles triangle osteotomy of distal humerus and Kirschner wire fixation with tension band from October 2014 to October 2019, were retrospectively analyzed. There were 13 males and 7 females, aged from 3.2 to 13.5 years old, the median age was 6.65 years old. PACS system was applied for the osteotomy design preoperatively, simulating and measuring the side length of isosceles triangle osteotomy. Then, Photoshop system was used to simulate the preoperative and postoperative osteotomy graphics, which could guide precise osteotomy during operation.@*RESULTS@#All the 20 patients were followed up for 20 to 24 months, with a median of 22.5 months. At the last follow-up, the carrying angle of the affected limb was 5 ° to 13 °, with a median of 8.3 °. The clinical efficacy was evaluated according to the Flynn elbow function score:excellent in 16 cases, good in 2 cases, and fair in 2 cases.@*CONCLUSION@#The treatment of cubitus varus in children by isosceles triangle osteotomy and Kirschner wire fixation with tension band assisted by PACS and Photoshop system has shown good clinical outcome.

CiteSpace knowledge map of research hotspots and frontiers of Polygalae Radix / 中国中药杂志

In this study, the Web of Science and China National Knowledge Infrastructure(CNKI) were searched comprehensively for the literature about the research on Polygalae Radix. After manual screening, 1 207 Chinese articles and 263 English articles were included in this study. Excel was used to draw the line chart of the annual number of relevant publications. CiteSpace 6.1.R3 was used for the visual analysis of author cooperation, publishing institutions, keyword co-occurrence, keyword clustering, and bursts in the research on Polygalae Radix. The results showed that the number of articles published in Chinese and English increased linearly, which indicated the rising research popularity of Polygalae Radix. WANG J and LIU X were the authors publishing the most articles in Chinese and English, respectively. Shanxi University of Chinese Medicine and Chinese Academy of Medical Sciences were the research institutions with the largest number of Chinese and English publications in this field, respectively. The institutions publishing the relevant articles in English formed a system with the Chinese Academy of Medical Sciences as the core. According to the keywords, the research hotspots of Polygalae Radix included variety selection and breeding, quality standard, extraction and identification of active chemical components, prescription compatibility, processing, clinical medication rules, and pharmacological mechanism. The research frontiers were the molecular mechanisms of Polygalae Radix and its active components in exerting the protective effect on brain nerve, regulating receptor pathways, alleviating anxiety and Alzheimer's disease, as well as data mining and clinical medication summary. This study has reference significance for the topic selection and frontier identification of the future research on Polygalae Radix.

Thoughts of treatment of tumor diseases based on toxic pathogen theory / 中国中药杂志

The toxic pathogen theory, an important part of the theories of traditional Chinese medicine(TCM), began in the Qin and Han dynasties, formed in the Jin, Sui, Tang, and Song dynasties, developed rapidly in the Ming and Qing dynasties, and conti-nued to develop in contemporary times based on the achievements of its predecessors. The continuous exploration, practice, and inheri-tance of many medical practitioners over the generations have facilitated the enrichment of its connotation. The toxic pathogen is violent, fierce, dangerous, prolonged, rapid in transmission, easy to hurt the internal organs, hidden, and latent, with many changes, and it is closely related to the development of tumor diseases. TCM has a history of thousands of years in the prevention and treatment of tumor diseases. It is gradually realized that the etiology of tumor is mainly attributed to the deficiency of healthy Qi and excess of to-xic pathogen, and the struggle between healthy Qi and toxic pathogen runs through the whole course of tumor, with the deficiency of healthy Qi as the prerequisite and the invasion of toxic pathogen as the root of the occurrence. The toxic pathogen has a strong carcinogenic effect and is involved in the whole process of tumor development, which is closely related to the malignant behaviors of tumors, including proliferation, invasion, and metastasis. This study discussed the historical origin and modern interpretation of the toxic pathogen theory in the prevention and treatment of tumors, with aims of sorting out the theoretical system based on the toxic pathogen theory in the treatment of tumor diseases, and illustrating the importance of the toxic pathogen theory in the treatment of tumors in the context of modern research on pharmacological mechanisms and the development and marketing of relevant anti-tumor Chinese medicinal preparations.