Effects of GW501516 on the injury of pulmonary artery endothelial cells induced by hypoxia and its mechanism / 中国药房

OBJECTIVE To investigate the effects of the peroxisome proliferator-activated receptors δ （PPARδ） agonist GW501516 on the injury of pulmonary artery endothelial cells （PAECs） induced by hypoxia and its mechanism. METHODS The cytotoxic effects of GW501516 were observed by detecting the relative survival rate of PAECs； the protein expression of PPARδ was determined by Western blot assay. The cellular model of PAECs injury was established under hypoxic conditions； using antioxidant N-acetylcysteine （NAC） as positive control， the effects of GW501516 on cell injury and reactive oxygen species （ROS） production were investigated by detecting cell apoptotic rate， cell viability， lactate dehydrogenase （LDH） activity and ROS levels. Using nuclear factor erythroid 2-related factor 2（Nrf2） activator dimethyl fumarate （DMF） as positive control， PAECs were incubated with GW501516 and/or Nrf2 inhibitor ML385 under hypoxic conditions； the mechanism of GW501516 on PAECs injury induced by hypoxia was investigated by detecting cell injury （cell apoptosis， cell viability， LDH activity）， the levels of superoxide dismutase （SOD）， glutathione peroxidase （GPx）， catalase （CAT）， malondialdehyde （MDA） and ROS， the expressions of Nrf2， heme oxygenase-1 （HO-1） and cleaved-caspase-3 （C-caspase-3） protein. RESULTS The results demonstrated that hypoxia inhibited the protein expression of PPARδ （P＜0.05）， while GW501516 promoted the protein expression of PPARδ in hypoxia- exposed PAECs without obvious cytotoxic effects. GW501516 inhibited the apoptosis of PAECs， improved cell viability， and reduced LDH activity and ROS levels. GW501516 could up-regulate the protein expression of HO-1 in PAECs and the levels of SOD， GPx and CAT， while down-regulated the levels of MDA and ROS by activating the Nrf2 pathway （P＜0.05）； but Nrf2 inhibitor ML385 could reverse the above effects of GW501516 （P＜0.05）. GW501516 exerted similar effects to Nrf2 activator DMF in down-regulating the expression of C-caspase-3 and inhibiting the injury of PAECs under conditions of hypoxia （P＜0.05）. Moreover， Nrf2 inhibitor ML385 reversed the 163.com inhibition effects of GW501516 on PAECs injury （P＜0.05）. CONCLUSIONS GW501516 can relieve the hypoxia-induced injury of PAECs via the inhibition of oxidative stress， the mechanism of which may be associated with activating Nrf2.

Analysis of 9 cases of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis / 中华儿科杂志

Objective: To analyze the clinical features,treatment and prognosis of drug induced hypersensitivity syndrome related hemophagocytic lymphohistiocytosis (DIHS-HLH). Methods: This was a retrospective case study. Clinical characteristics, laboratory results, treatment and prognosis of 9 patients diagnosed with DIHS-HLH in Beijing Children's hospital between January 2020 and December 2022 were summarized. Kaplan-Meier survival analysis was used to calculate the overall survival rate. Results: Among all 9 cases, there were 6 males and 3 females, with the age ranged from 0.8 to 3.1 years. All patients had fever, rash, hepatomegaly and multiple lymph node enlargement. Other manifestations included splenomegaly (4 cases), pulmonary imaging abnormalities (6 cases), central nervous system symptoms (3 cases), and watery diarrhea (3 cases). Most patients showed high levels of soluble-CD25 (8 cases), hepatic dysfunction (7 cases) and hyperferritinemia (7 cases). Other laboratory abnormalities included hemophagocytosis in bone marrow (5 cases), hypofibrinogenemia (3 cases) and hypertriglyceridemia (2 cases). Ascending levels of interleukin (IL) 5, IL-8 and interferon-γ (IFN-γ) were detected in more than 6 patients. All patients received high dose intravenous immunoglobulin, corticosteroid and ruxolitinib, among which 4 patients were also treated with high dose methylprednisolone, 2 patients with etoposide and 2 patients with cyclosporin A. After following up for 0.2-38.6 months, 7 patients survived, and the 1-year overall survival rate was (78±14)%. Two patients who had no response to high dose immunoglobulin, methylprednisolone 2 mg/(kg·d) and ruxolitinib died. Watery diarrhea, increased levels of IL-5 and IL-8 and decreased IgM were more frequently in patients who did not survive. Conclusions: For children with fever, rash and a suspicious medication history, when complicated with hepatomegaly, impaired liver function and high levels of IL-5 and IL-8, DIHS-HLH should be considered. Once diagnosed with DIHS-HLH, suspicious drugs should be stopped immediately, and high dose intravenous immunoglobulin, corticosteroid and ruxolitinib could be used to control disease.

Anti-cancer Effect of Traditional Chinese Medicine in Regulating Cellular Senescence： A Review / 中国实验方剂学杂志

In recent years， the incidence and mortality rates of cancer have been increasing， posing a serious threat to human health. Western medicine mainly uses treatments such as surgical resection， chemotherapy， immunotherapy and targeted therapy， but they are prone to complications， drug resistance and adverse reactions. A growing number of studies have shown that traditional Chinese medicine has obvious advantages in the treatment of cancer， reducing the recurrence rate of cancer and improving the quality of survival of patients. Cellular senescence refers to a state of irreversible cell cycle growth arrest when cells cease to proliferate after a limited number of divisions， resulting in a decline in cell proliferation and differentiation capacities and physiological functions， accompanied by morphological changes such as flattening and multinuclear morphology. At the molecular level， it shows increased expression of DNA damage-related genes， reduced expression of cell cycle-related factors and significant secretory activity. The malignant development of cancer is closely related to cellular senescence. With the increasing number of cancer cell proliferation， cancer-related genes undergo continuous mutations， freeing them from cellular senescence and thus achieving unlimited proliferation. Through recent studies， it has been found that induction of tumor cell senescence， possibly through modulation of cellular DNA damage， cell cycle arrest and senescence-associated secretory phenotype （SASP）， which converts the suppressive immune tumor microenvironment to an activated immune tumor microenvironment and thus reverses the escape of tumor cell senescence， is a promising strategy for cancer therapy. However， the mechanism of cellular senescence in cancer progression is not fully understood， especially the anti-cancer role played by traditional Chinese medicine in regulating cellular senescence. This article summarized and concluded the specific molecular mechanisms of cellular senescence， the role of cellular senescence in cancer progression， and the mechanism of anti-cancer effects of traditional Chinese medicine based on cellular senescence from the perspective of regulating cellular senescence， with a view to providing ideas and methods for the anti-cancer effects of traditional Chinese medicine and the development of new drugs.

Clinical application of sectional feldspathic porcelain veneers in maxillary midline diastema closure / 中华口腔医学杂志

The presence of midline diastema is a common complaint of patients that may affect dentofacial esthetics. This article summarized the etiology of maxillary midline diastema, and introduced the clinical application of sectional feldspathic porcelain veneers in maxillary midline diastema closure, including indication selection as well as clinical procedure. It aimed to provide an alternative solution on clinical treatment of maxillary midline diastema.

Cross-sectional study on the use of masks among occupational groups with high-risk positions for overseas import and pollution transmission / 中华劳动卫生职业病杂志

Objective: To investigate the wearing of masks and the knowledge of masks among high-risk positions for overseas import and pollution transmission. Methods: From May 14 to 17, 2022, a convenient sampling method was used to conduct an online survey among 963 workers in high-risk positions for overseas import and pollution transmission in Beijing. The behaviors of individual use and wearing masks, the distribution and supervision of the unit, the knowledge of personal mask protection and the subjective feelings of wearing masks were analyzed. The χ(2) test and logistic regression model were used to analyze the influencing factors of the correct selection of masks. Results: The majority of the workers in high-risk positions for overseas import and pollution transmission were male (86.0%, 828/963), age concentration in 18-44 years old (68.2%, 657/963), and the majority of them had college or bachelor degrees (49.4%, 476/963). 79.4%(765/963) of the workers chose the right type of masks, female, 45-59 years old and high school education or above were the risk factors for correct selection of masks (P <0.05). Workers had good behaviors such as wearing/removing masks, but only 10.5% (101/963) could correctly rank the protective effect of different masks. 98.4% (948/963) of the workers believed that their work units had provided masks to their employees, and 99.1% (954/963) and 98.2%(946/963) of them had organized training and supervision on the use of masks, respectively. 47.4%(456/963) of the workers were uncomfortable while wearing masks. Conclusion: The overall selection and use of masks among occupational groups in high-risk positions for overseas import and pollution transmission in China need to be further standardized. It is necessary to strengthen supervision and inspection on the use of masks among occupational groups, and take improvement measures to improve the comfort of wearing masks.

Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection / 中华妇产科杂志

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer / 中华肿瘤杂志

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

Diagnosis of a case with Hermansky-Pudlak syndrome type 5 through high-throughput sequencing and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a patient with Hermansky-Pudlak syndrome type 5 (HPS-5).@*METHODS@#A child with HPS-5 who had attended the Children's Hospital Affiliated to Shandong University on October 3, 2019 was selected as the study subject. Clinical data of the child were collected. Genetic variant was analyzed through high-throughput sequencing. A literature review was also carried out.@*RESULTS@#The child, a 1-year-and-5-month-old girl, had nystagmus since childhood, lost of retinal pigmentation by fundus examination and easy bruising. High-throughput sequencing revealed that she has harbored compound heterozygous variants of the HPS5 gene, namely c.1562_1563delAA (p.F521Sfs*27) and c.1404C>A (p.C468X), which were inherited from his father and mother, respectively. Based on the guidelines from the American College for Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS+PM2_Supporting+PM3+PP4). Among 18 previously reported HPS-5 patients, all had had eye problems, and most of them had tendency for bleeding. Eight cases had carried compound heterozygous variants of the HPS5 gene, 8 carried homozygous variants, 2 carried double homozygous variants, and most of them were null mutations.@*CONCLUSION@#The c.1562_1563delAA(p.F521Sfs*27) and c.1404C>A (p.C468X) compound heterozygous variants of the HPS5 gene probably underlay the HPS-5 in this child. High-throughput sequencing has provided an important tool for the diagnosis. HSP-5 patients usually have typical ocular albinism and/or oculocutaneous albinism and tendency of bleeding, which are commonly caused by compound heterozygous and homozygous variants of the HPS5 gene, though serious complications have been rare.

Clinical and genetic analysis of a very early-onset inflammatory bowel disease type 28 child with atypical clinical manifestation / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease (VEO-IBD) type 28 child with atypical clinical manifestations.@*METHODS@#A VEO-IBD type 28 child with atypical clinical manifestations admitted to the Department of Neonatology, Children's Hospital Affiliated to Shandong University on November 5, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 50-day-old male, had manifested bronchitis, ulcerative stomatitis, eczema and slightly loose stool. High-throughput sequencing revealed that he has harbored compound heterozygous variants of the IL-10RA gene, namely c.299T>G (p.V100G) and c.301C>T (p.R101W), which were inherited from his father and mother, respectively. Bioinformatic analysis showed that both variants have been recorded in the HGMD database, though the c.299T>G variant has not been included in the gnomAD, 1000 Genomes, ExAC and ESP6500 databases, while the c.301C>T variant has a low population frequency. Both variants were predicted to be deleterious by the online software including SIFT, PolyPhen-2 and Mutation Taster. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PS3+PM2_Supporting+PP3).@*CONCLUSION@#The c.299T>G and c.301C>T variants of the IL-10RA gene probably underlay the VEO-IBD type 28 in this child. Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.

Preliminary observation on the clinical application of rehabilitation support for lumbar disc herniation based on 3D printing technology / 中国骨伤

OBJECTIVE@#To analyze the important effect of 3D printing personalized lumbar support on lumbar pain and lumbar function in patients with lumbar disc herniation.@*METHODS@#From October 2018 to May 2021, 60 patients initially diagnosed with lumbar disc herniation were selected and divided into an observation group and a control group, with 30 patients in each group. Among them, there were 18 males and 12 females in the observation group;the age ranged from 24 to 56 years old, with an average of (45.23±6.07) years old. The course of disease ranged from 1 to 24 months, with an average of(6.25±0.82) months, and rehabilitation treatment was carried out by wearing 3D printed personalized lumbar support. There were 19 males and 11 females in the control group;the age ranged from 25 to 57 years old, with an average of (42.78±7.58) years old. The course of disease ranged from 1 to 24 months, with an average of (6.72±1.36) months, and rehabilitation treatment is carried out by wearing traditional lumbar protective equipment. The Japanese Orthopaedic Association (JOA) scores, lumbar Oswestry dysfunction index (ODI) and visual analogue scale (VAS) were evaluated and compared between the two groups before and 1 course after treatment (3 weeks).@*RESULTS@#There was no statistically significant difference in JOA, ODI, and VAS between two groups before treatment (P>0.05). After one course of treatment (3 weeks), JOA scores of both groups was increased compared to before treatment (P<0.05), while ODI and VAS decreased compared to before treatment (P<0.05). After treatment, JOA score of observation group was higher than that of control group (P<0.05), while ODI and VAS scores were lower than those of control group. No adverse events occurred in both groups.@*CONCLUSION@#The application of 3D printing personalized lumbar support can effectively alleviate the pain of patients with lumbar disc herniation and improve their lumbar function of patients.

Effect of Different Antitumor Regimens on Incidence and Severity of Corona Virus Disease 2019 Pneumonia in Lung Cancer Patients: A Single-center Retrospective Study / 中国肺癌杂志

BACKGROUND@#Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population.@*METHODS@#From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models.@*RESULTS@#(1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity.@*CONCLUSIONS@#Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.

Association between serum alkaline phosphatase and type 2 diabetes mellitus with nonalcoholic fatty liver disease / 临床肝胆病杂志

Objective To investigate the association between serum alkaline phosphatase (ALP) and type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Methods A total of 599 patients with T2DM who were hospitalized in Department of Endocrinology, Affiliated Hospital of Jiangsu University, from July 2016 to December 2018 were enrolled as subjects. According to the presence or absence of NAFLD, the patients were divided into NAFLD group with 286 patients and non-NAFLD group with 313 patients, and according to the results of abdominal ultrasound, the patients with NAFLD were divided into mild group with 111 patients, moderate group with 105 patients, and severe group with 70 patients. General clinical data were compared between groups. The independent samples t - test was used for comparison of normally distributed continuous data between two groups, and an analysis of variance was used for comparison between three groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups; the chi-square test was used for comparison of categorical data between groups. Pearson correlation analysis and Spearman correlation analysis were used to investigate the correlation between ALP and clinical indices, and a logistic regression analysis was used to investigate the influencing factors for NAFLD. Results Compared with the non-NAFLD group, the NAFLD group had significantly higher proportion of patients with history of hypertension ( χ 2 =7.864, P < 0.05), systolic blood pressure ( t =-2.226, P < 0.05), diastolic blood pressure ( t =-3.800, P < 0.05), body mass index (BMI) ( t =-11.842, P < 0.05), waist circumference (WC) ( t =-9.150, P < 0.05), fasting insulin (FINS) ( Z =-6.173, P < 0.05), fasting C-peptide ( t =-5.419, P < 0.05), serum uric acid ( t =-4.957, P < 0.05), low-density lipoprotein cholesterol ( t =-2.702, P < 0.05), triglyceride ( Z =-9.376, P < 0.05), total cholesterol (TC) ( t =-3.016, P < 0.05), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ( Z =-5.794, P < 0.05), alanine aminotransferase (ALT) ( Z =-6.737, P < 0.05), aspartate aminotransferase (AST) ( Z =-4.389, P < 0.05), gamma-glutamyl transpeptidase (GGT) ( Z =-7.764, P < 0.05), and ALP ( t =-2.833, P < 0.05), as well as significantly lower age ( t =2.184, P < 0.05) and high-density lipoprotein cholesterol ( Z =-5.273, P < 0.05). The severity of NAFLD (mild, moderate or severe) was positively correlated with age ( r s =0.140, P < 0.05), BMI ( r s =0.239, P < 0.05), WC ( r s =0.222, P < 0.05), FINS ( r s =0.191, P < 0.05), HOMA-IR ( r s =0.218, P < 0.05), ALT ( r s =0.188, P < 0.05), AST ( r s =0.279, P < 0.05), GGT ( r s =0.202, P < 0.05), and ALP ( r s =0.361, P < 0.05). In the patients with T2DM and NAFLD, ALP was positively correlated with HbAlc ( r =0.149, P < 0.05), fasting plasma glucose ( r =0.146, P < 0.05), HOMA-IR ( r s =0.132, P < 0.05), TC ( r =0.151, P < 0.05), ALT ( r s =0.210, P < 0.05), AST ( r s =0.192, P < 0.05), and GGT ( r s =0.297, P < 0.05). The logistic regression analysis showed that ALP was an influencing factor for NAFLD in patients with T2DM (odds ratio=1.013, 95% confidence interval: 1.004-1.023, P < 0.05). Conclusion Elevated serum ALP is a risk factor for T2DM with NAFLD and is closely associated with hyperglycemia, insulin resistance, and hyperlipemia, and ALP may play a role in the development and progression of T2DM and NAFLD.

Phosphodiesterase 5 Inhibitors Attenuate Unilateral Ureteral Obstruction-Induced Renal Fibrosis / 中山大学学报(医学科学版)

ObjectiveTo investigate whether phosphodiesterase （PDE） 5 inhibitors sildenafil （SIL） or LW1646 prevented renal interstitial fibrosis induced by unilateral ureteral obstruction （UUO）. MethodsMale C57BL/6 mice were randomly divided into four groups （n =6）， namely the Sham group， 7UUO group， 7UUO+SIL group and 7UUO+LW1646 group. Sildenafil （SIL） or LW1646， or vehicle was administered 1 hour before surgery， and the mice were continuously treated once daily （i. g.， 50 mg/kg） for 7 days. The obstructed kidneys were harvested on day 7. Hematoxylin-eosin （HE） and Masson’s staining was used to examine renal histology. Immunoblotting and RT-qPCR were used to detect the expression levels of protein and mRNA for fibrosis， apoptosis， endoplasmic reticulum （ER） stress， autophagy， and pro-fibrotic factors. Human proximal tubule epithelial cells （HK-2） were treated with TGF-β1 for 48 hours or tunicamycin for 24 hours， respectively， to evaluate whether cyclic guanosine monophosphate （cGMP） or PDE5 inhibitors prevents ER stress and pro-fibrotic responses. ResultsAt the 7th days after UUO， the body weight of the mice showed a significant decrease （P< 0.000 1） compared with that in the sham group. The obstructed kidneys showed a significant tubular dilation and interstitial inflammation. The levels of protein and mRNA expression in apoptosis， ER stress， autophagy-related protein and pro-fibrotic factors were also markedly increased in UUO mice （P <0.05）. In contrast， SIL or LW1646 treatment was associated with attenuated tubular dilation， infiltration of inflammatory cells and collagen content in the obstructed kidney of the mice. The protein and mRNA expression levels of renal TGF-β1 were markedly decreased， and the protein expression levels of apoptosis， endoplasmic reticulum stress， and autophagy markers were also significantly downregulated by PDE5 inhibitors. In HK-2 cells， TGF-β1 induced increased expression levels of fibronectin and BiP， which was at least partially reversed by cGMP， a product of PDE inhibition. Additionally， PDE5 inhibitors were found to modulate aberrant levels of autophagy and apoptosis. ConclusionIn conclusion， PDE5 inhibitors， in particular， LW1646， can alleviate the progression of fibrosis by improving ER stress， apoptosis and autophagy as well as downregulating protein and mRNA expression of TGF-β1.

Discussion on the establishment of the discipline of "organ donation" / 器官移植

Vivid and abundant social practice constantly creates new understanding, which will inevitably lead to the emergence of new disciplines. Organ donation discipline is involved with multiple disciplines, such as ethics, law, medicine, sociology and psychology, etc. After entering a new stage of high-quality development, whether it is necessary to establish the discipline of "organ donation" is worthy of discussion. According to the basic standards for establishing a new discipline, groundbreaking achievements in organ donation could lay a solid foundation for the establishment of "organ donation" discipline. However, current conditions for the establishment of "organ donation" are not fully mature, and the process of discipline establishment will absolutely encounter resistance. In the future, the scope and orientation of organ donation should be further elucidated, and a series of measures should be taken, such as establishing independent academic organizations, offering organ donation courses, carrying out special research and innovation, and strengthening international cooperation and exchanges, aiming to promote the establishment of organ donation discipline. The cooperation between academic community and governments is the key to promote the establishment of the discipline of organ donation. Governments will make final decisions by comprehensively considering the investment of resources, development needs of the discipline and the relationship among existing disciplines.

Efficacy analysis of autologous facet joint bone block in lumbar interbody fusion of osteoporosis patients / 北京大学学报(医学版)

OBJECTIVE@#To compare and analyze the feasibility of autologous facet joint bone block as an alternative to polyetheretherketone (PEEK) cage in lumbar intervertebral fusion surgery for patients with osteoporosis.@*METHODS@#From December 2018 to June 2021, the case data of patients with osteoporosis (T value ≤ -2.5 on dual energy X-ray bone density) who underwent posterior lumbar interbody fusion in the Fourth Medical Center, Chinese PLA General Hospital were retrospectively reviewed. All the cases were followed up for no less than 12 months and were divided into two groups according to the differences of interbody fusion materials: the autologous facet joint bone block group (autogenous bone group) and the PEEK cage group (PEEK group). The general data [such as age, gender, body mass index (BMI), primary diagnosis, distribution of fusion segments, bone mineral density of lumbar (BMD), incidence of preoperative complications], the perioperative data (such as duration of operation, intraoperative blood loss, postoperative drainage, perioperative allogeneic blood transfusion rate), and the incidence of postoperative complications were compared between the two groups. Imaging parameters (disc height, lumbar lordosis angle, segment lordosis angle, segmental lordosis angle, disc height improvement rate, and fusion rate) and lumbar functional scores [visual analogue scale (VAS), Oswestry disability index (ODI), Japanese Orthopedics Association (JOA) score for lower back pain] were compared to evaluate the clinical efficacy between the kinds of intervertebral fusion materials 1 week, 3 months and 6 months postoperative and at the last follow-up.@*RESULTS@#A total of 118 patients were enrolled, including 68 cases in the autogenous bone group and 50 cases in the PEEK group, there were no statistical differences in age, gender, BMI, primary diagnosis, distribution of fusion segments, BMD, incidence of preoperative complications, duration of operation, intraoperative blood loss, postoperative drainage, perioperative allogeneic blood transfusion rate, incidence of postoperative complications, all the preoperative imaging parameters and all the lumbar function scores between the two groups (P>0.05). Postoperative superficial surgical site infections occurred in 3 patients in the autogenous bone group and 2 patients in the PEEK group. At the last follow-up, 3 cases of intervertebral graft collapse occurred in the autogenous bone group and 5 cases in the PEEK group, 1 case of graft subsidence in the autogenous bone group and 1 case in the PEEK group. All the imaging parameters showed significant differences between postoperation and preoperation (P < 0.05), and all the imaging parameters showed significant differences between 1 week and 3 months postoperative in both groups (P < 0.05). The height, angle of fusion gap in the autogenous bone group were lower than those in the PEEK group 1 week postoperatively (P < 0.05), and the fusion gap height improvement rate in the autogenous bone group was lower than that in the PEEK group (P < 0.05). The cases in both groups started to show final fusion 3 months after surgery, and the fusion rate in the autogenous bone group was 75% 6 months postoperatively, which was significantly higher than the rate of 56% in the PEEK group (P < 0.05), and there was no statistically significant difference in the final fusion rate between the two groups (P>0.05). The ODI, the postoperative VAS score was significantly lower than that in preoperation, while the postoperative JOA score was significantly higher than that in preoperation (P < 0.05). The ODI was lower while the JOA score was higher of the autogenous bone group than that of the PEEK group 6 months postoperatively (P < 0.05).@*CONCLUSION@#In osteoporosis patients, good interbody fusion rate and improvement of lumbar vertebral function can be obtained by using autologous facet joint bone block or PEEK cage, while the fusion rate and the improvement of lumbar function with autologous facet joint bone block are better than those with PEEK cage 6 months post-operatively. PEEK cage is superior to autologous facet joint bone block in intervertebral distraction and improvement of lumbar lordosis. Significant disc space subsidence occurred in osteoporotic patients within 3 months after lumbar interbody fusion, and the subsidence of PEEK cage was more obvious than that of autologous facet joint bone block.

Mutations of PTCH1 gene in two pedigrees with bifid rib-basal cell nevus-jaw cyst syndrome / 浙江大学学报·医学版

Two male patients with bifid rib-basal cell nevus-jaw cyst syndrome (BCNS) were admitted to Department of Stomatology, the First Affiliated Hospital of Bengbu Medical College due to radiological findings of multiple low density shadows in the jaw. Clinical and imaging findings showed thoracic malformation, calcification of the tentorium cerebellum and falx cerebrum as well as widening of the orbital distance. Whole exon high-throughput sequencing was performed in two patients and their family members. The heterozygous mutations of c.C2541C>A(p.Y847X) and c.C1501C>T(p.Q501X) in PTCH1 gene were detected in both patients. Diagnosis of BCNS was confirmed. The heterozygous mutations of PTCH1 gene locus were also found in the mothers of the two probands. Proband 1 showed clinical manifestations of low intelligence, and heterozygous mutations of c.C2141T(p.P714L) and c.G3343A(p.V1115I) were detected in FANCD2 gene. Proband 2 had normal intelligence and no FANCD2 mutation. The fenestration decompression and curettage of jaw cyst were performed in both patients. Regular follow-up showed good bone growth at the original lesion, and no recurrence has been observed so far.

Application of Microhaplotypes in Sibling Kinship Testing / 法医学杂志

OBJECTIVES@#To investigate the efficacy of different numbers of microhaplotype (MH) loci and the introduction of different reference samples on the identification of full sibling, half sibling and differentiation between full sibling and half sibling kinships, and to explore the effect of changing mutation rate on sibling testing.@*METHODS@#First, a family map involving three generations was established, and four full sibling identification models, five half sibling identification models and five models distinguishing full and half siblings were constructed for different reference samples introduced. Based on the results of the previous study, two sets of nonbinary SNP-MH containing 34 and 54 loci were selected. Based on the above MH loci, 100 000 pairs of full sibling vs. unrelated individuals, 100 000 pairs of half sibling vs. unrelated individuals and 100 000 pairs of full sibling vs. half sibling were simulated based on the corresponding sibling kinship testing models, and the efficacy of each sibling kinship testing model was analyzed by the likelihood ratio algorithm under different thresholds. The mutant rate of 54 MH loci was changed to analyze the effect of mutation rate on sibling identification.@*RESULTS@#In the same relationship testing model, the systematic efficacy of sibling testing was positively correlated with the number of MH loci detected. With the same number of MH loci, the efficacy of full sibling testing was better than that of uncle or grandfather when the reference sample introduced was a full sibling of A, but there was no significant difference in the identification efficacy of the four reference samples introduced for full sibling and half sibling differentiation testing. In addition, the mutation rate had a slight effect on the efficacy of sibling kinship testing.@*CONCLUSIONS@#Increasing the number of MH loci and introducing reference samples of known relatives can increase the efficacy of full sibling testing, half sibling testing, and differentiation between full and half sibling kinships. The level of mutation rate in sibling testing by likelihood ratio method has a slight but insignificant effect on the efficacy.

Correlation of the duration of preoperative biliary drainage and postoperative complications after pancreaticoduodenectomy / 肿瘤研究与临床

Objective:To investigate the effect of the duration of preoperative biliary drainage on postoperative complications after pancreaticoduodenectomy.Methods:The clinical data of 102 patients with benign and malignant hepatopancreatic ductal periampullary tumors who underwent pancreaticoduodenectomy and preoperative biliary drainage in Beijing Friendship Hospital, Capital Medical University from January 2016 to July 2020 were retrospectively analyzed. According to the median duration of preoperative biliary drainage, the patients were divided into short-term drainage group (≤ the median duration of biliary drainage) and long-term drainage group (> the median duration of biliary drainage). The general data, the effect of biliary drainage, inflammation-related indicators and postoperative complications were compared between the two groups. Multivariate logistic regression was used to screen the risk factors related to the postoperative severe complications.Results:Of the 102 patients, 68 (66.7%) were males and 34 (33.3%) were females, with a median age of 63 years (43-80 years). The median duration of preoperative biliary drainage was 14 d. There were 68 patients in short-term drainage group and 34 patients in long-term drainage group. There were no statistically significant differences in age, gender, body mass index (BMI), hypertension, diabetes mellitus, surgery history of upper abdominal, American Society of Anesthesiologists (ASA) grade, carcinoembryonic antigen, carbohydrate antigen 125, alpha-fetoprotein, prothrombin time, pancreaticojejunostomy method, operation time, and pathological type between the two groups (all P > 0.05). However, patients in long-term drainage group had higher conversion rate, more blood loss and longer hospital stay compared with those in short-term drainage group (all P < 0.05). Before biliary drainage, alanine aminotransferase (ALT) level in short-term drainage group was higher than that in long-term drainage group ( Z = -2.59, P = 0.009), and there were no statistically significant differences in aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TB) and direct bilirubin (DB) levels between the two groups before biliary drainage (all P > 0.05). After biliary drainage, DB in short-term drainage group was higher than that in long-term drainage group ( Z = -3.34, P = 0.001), and there was no statistically significant difference in ALT, AST, ALB, TB levels between the two groups (all P > 0.05). There were no statistically significant differences in the levels of white blood cells, neutrophils, lymphocytes and the ratio of neutrophils to lymphocytes between the two groups on the 1st and 3rd day after the operation (all P > 0.05). The total incidence of postoperative related complications in short-term drainage group and long-term drainage group was 63.2% (43/68), 70.6% (24/34), respectively, and the difference was statistically significant ( χ2 = 0.54, P = 0.461); the incidences of bile leakage, abdominal or gastrointestinal bleeding, intra-abdominal infection, delayed gastric emptying, all grades of pancreatic leakage, grade B and C pancreatic leakage were not statistically different between the two groups (all P > 0.05); the incidence of severe postoperative related complications in short-term drainage group was higher than that in long-term drainage group [27.9% (19/68) vs. 8.8% (3/34), χ2 = 4.90, P = 0.027]. Multivariate logistic regression analysis showed that the long-term preoperative biliary drainage was an independent protective factor for postoperative severe complications (long-term drainage vs. short-term drainage: OR = 0.253, 95% CI 0.066-0.975, P = 0.046), while BMI ( OR = 1.174, 95% CI 0.986-1.398, P = 0.071) and pathological type (benign or borderline vs. malignant tumor: OR = 0.247, 95% CI 0.043-1.419, P = 0.117) were not independent influencing factors for postoperative severe complications. Conclusions:Short-term biliary drainage (≤14 d) is a risk factor for postoperative severe complications in patients with hepatopancreatic ductal periampullary tumor undergoing preoperative biliary drainage. Preoperative biliary drainage time is not associated with postoperative total complications, pancreatic leakage, bile leakage, abdominal or gastrointestinal bleeding, intra-abdominal infection, delayed gastric emptying.

Prevalence survey of clinical manifestations following COVID-19 / 中华麻醉学杂志

Objective:To investigate the clinical manifestations of population following COVID-19 by using questionnaires.Methods:COVID-19 among anesthesia workers and the surrounding population was investigated between 11 November 2022 and 31 December 2022 in China.The Tencent electronic questionnaire(ID.11492813) was sent to different WeChat groups of the Association of Anesthesiologists or Society of Anesthesiologists via the WeChat platform of the medical personnel in China. The survey was conducted between January 7 and January 15, 2023. Results:A total of 17 000 questionnaires were issued for this survey, 11 060 valid questionnaires from 31 provinces and autonomous regions were collected all over the country, with a recovery rate of 65.059%.There were 10068 (91.037%) participants diagnosed as having COVID-19, and among of them, 47.606% were male and 52.394% were female. The main post-COVID-19 clinical manifestations included fever (85.777%), cough (83.731%), fatigue (75.338%), parasomnia (64.352%), limb soreness (58.890%), dizziness, headache, tinnitus (38.617%), loss or abnormality of taste (37.763%), and loss or abnormality of smell (30.960%); peripheral neuralgia was usually found within 3 days after positive nucleic acid test or positive antigen test; there were 2 963 cases accompanied with sweating, and among of them, 47.25% were male and 52.75% were female, and 37.80% of these participants continued to sweat after the nucleic acid test or antigen test became negative. There were 1 151 cases with premature heart beats among the study population, and the symptoms aggravated following COVID-19 were found in 34.32% of these patients.Conclusions:In addition to the respiratory system, the central and peripheral nerves of patients are also affected following COVID-19, and the peripheral and central nerve disorders last until several days after negative nucleic acid test or antigen test, suggesting that anesthesiologists should pay more attention to monitoring of various nerve function and impact of surgery and anesthetic drugs on the stress response of the body in such patients.

A case report of epididymal leiomyoma / 中华泌尿外科杂志

Leiomyomas are benign tumors that arise from smooth muscle cells and rarely involve the male genitourinary system. We reported a case of a patient who underwent radical orchiectomy for epididymal tumor. The postoperative pathological diagnosis was epididymal leiomyoma, and there was no recurrence after 9 months of follow-up.