Role of mesenchymal stem cells and their exosomes in the treatment of drug-induced liver injury / 临床肝胆病杂志

The incidence rate of drug-induced liver injury （DILI） is increasing year by year with unknown mechanisms， and the treatment methods for DILI mainly include drugs， liver support systems， and liver transplantation， all of which have certain limitations. Therefore， the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation， promoting hepatocyte proliferation and regeneration， inhibiting the apoptosis of hepatocytes， improving oxidative stress， and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI， so as to provide a reference for further research.

Incidence and risk factors of renal injury in human immunodeficiency virus infection/acquired immunodeficiency syndrome patients with poor immune reconstitution / 中华传染病杂志

Objective:To investigate the incidence and risk factors of renal injury in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients with poor immune reconstitution.Methods:The HIV infection/AIDS patients with poor immune reconstitution who were visited Second Department of Infection of Hangzhou Xixi Hospital from January to December 2021 were enrolled. The clinical data and laboratory examinations of the patients were collected, and the relevant risk factors were analyzed by logistic regression.Results:Among 303 HIV infection/AIDS patients with poor immune reconstitution, 59(19.5%) patients had renal injury. Logistic regression analysis showed that hypertension (odds ratio ( OR)=0.200, 95% confidence interval (95% CI) 0.065 to 0.618, P=0.005), taking tenofovir ( OR=0.275, 95% CI 0.130 to 0.580, P=0.001), hypoproteinemia ( OR=1.045, 95% CI 1.006 to 1.086, P=0.022), and low CD4 + T lymphocytes level ( OR=1.009, 95% CI 1.003 to 1.014, P=0.001) were risk factors for renal injury. Conclusions:The incidence of renal injury in HIV infection/AIDS patients with poor immune reconstitution is high. Hypertension, taking tenofovir, hypoproteinemia, and low CD4 + T lymphocytes level are risk factors for renal injury in patients.

Association of inhibitory receptor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain with immune disorders in chronic HBV infection / 临床肝胆病杂志

Persistent HBV infection alters the expression of receptors on the surface of innate and acquired immune cells, which may cause a variety of immune disorders and finally lead to immune escape and disease chronicity. Studies have shown that the upregulation of inhibitory receptors is the main cause of immune disorders in patients, and blocking inhibitory receptors can restore immune function to a certain extent. T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a new type of inhibitory receptor attracting much attention at present, and it is highly expressed in NK cells and T cells. It has been found that TIGIT plays an important role in chronic viral infection, and this article briefly reviews the research advances in the association between TIGIT and immune disorders in chronic HBV infection.

Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies / 医学前沿

Immunotherapies based on immune checkpoint blockade (ICB) have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade. To date, immune checkpoint inhibitors (ICIs) of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy. Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers, however, a large subset of refractory patients presents poor responsiveness to ICB therapy; and the underlying mechanism remains elusive. Recently, numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment (TME) with various products of metabolism, and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy. Nevertheless, a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance. Here, we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints (CTLA-4, PD-1, and PD-L1) to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.

Evaluation of botulinum toxin A injections for the treatment of glabellar lines by using high-frequency ultrasound / 中华皮肤科杂志

Objective To investigate changes in thickness of the skin and muscular layer during the treatment with botulinum toxin A injections in patients with glabellar lines.Methods Twenty-six subjects with moderate to severe glabellar lines were enrolled into this study,who received botulinum toxin A injections in Peking Union Medical College Hospital from August 2017 to February 2018.Before the injections,4 and 16 weeks after the injections,thickness of the dermis at the injection site was measured by using 50 MHz high-frequency ultrasound,and full thickness of the skin and thickness of the muscular layer were measured with 20 MHz high-frequency ultrasound.Repeated measures analysis of variance,paired ttest and Bonferroni method were used to compare the pretreatment and posttreatment tissue thicknesses measured by using high-frequency ultrasound.Results Before the injections,the thickness of the dermis,full thickness of the skin,thickness of the muscular layer were 2.01 ± 0.48,4.32 ± 0.73 and 4.51 ± 0.67 mm respectively.No significant difference was observed among the pretreatment,4-and 16-week posttreatment thickness of the dermis (F =1.94,P =0.199),while there were significant differences among the pretreatment,4-and 16-week posttreatment full thickness of the skin and thickness of the muscular layer (F =6.28,24.19,P =0.020,＜ 0.001 respectively).Four weeks after the injections,the full thickness of the skin significantly increased (4.88 ± 0.93 mm,t =3.72,P =0.004),while the thickness of the muscular layer significantly decreased (3.82 ± 0.79 mm,t =4.65,P =0.001)compared with the pretreatment thicknesses.Sixteen weeks after the injections,the full thickness of the skin (4.61 ± 0.73 mm) and thickness of the muscular layer (4.38 ± 0.90 mm) did not significantly differ from those before and 4 weeks after the injections (all P ＞ 0.016 7).Conclusions Botulinum toxin A injections can change the thickness of the subcutaneous tissue and muscular layer.High-frequency ultrasound can be applied to the evaluation of efficacy and to follow-up after the treatment of glabellar lines with botulinum toxin A injections.

NEDDylation antagonizes ubiquitination of proliferating cell nuclear antigen and regulates the recruitment of polymerase η in response to oxidative DNA damage

NEDDylation has been shown to participate in the DNA damage pathway, but the substrates of neural precursor cell expressed developmentally downregulated 8 (NEDD8) and the roles of NEDDylation involved in the DNA damage response (DDR) are largely unknown. Translesion synthesis (TLS) is a damage-tolerance mechanism, in which RAD18/RAD6-mediated monoubiquitinated proliferating cell nuclear antigen (PCNA) promotes recruitment of polymerase η (polη) to bypass lesions. Here we identify PCNA as a substrate of NEDD8, and show that E3 ligase RAD18-catalyzed PCNA NEDDylation antagonizes its ubiquitination. In addition, NEDP1 acts as the deNEDDylase of PCNA, and NEDP1 deletion enhances PCNA NEDDylation but reduces its ubiquitination. In response to HO stimulation, NEDP1 disassociates from PCNA and RAD18-dependent PCNA NEDDylation increases markedly after its ubiquitination. Impairment of NEDDylation by Ubc12 knockout enhances PCNA ubiquitination and promotes PCNA-polη interaction, while up-regulation of NEDDylation by NEDD8 overexpression or NEDP1 deletion reduces the excessive accumulation of ubiquitinated PCNA, thus inhibits PCNA-polη interaction and blocks polη foci formation. Moreover, Ubc12 knockout decreases cell sensitivity to HO-induced oxidative stress, but NEDP1 deletion aggravates this sensitivity. Collectively, our study elucidates the important role of NEDDylation in the DDR as a modulator of PCNA monoubiquitination and polη recruitment.

Topical drugs for the treatment of psoriasis / 中华皮肤科杂志

In recent years, great progress has been made in the pathogenesis of psoriasis, which has provided multiple new targets for the treatment of psoriasis, and ushered the treatment, especially topical treatment, of psoriasis to a new era. Some new targeted topical drugs with action mechanisms different from those of traditional drugs have been applied in clinical practice, which are mainly small -molecule inhibitors targeting cell signaling pathways or enzymes involved in the pathogenesis of psoriasis, such as the Janus kinase/signal transducer and activator of transcription(JAK/STAT) pathway, phosphodiesterase type 4 (PDE4), mitogen-activated/extracellular-signal-regulated kinase kinase (MEK), vascular endothelial growth factor receptor (VEGFR), tropomyosin receptor kinase A (TrKA), retinoic acid receptor-related orphan receptor γ (RORγ), and so on. At present, many phaseⅠ and Ⅱ clinical trials are conducted for these drugs. Some completed trials have shown that they have good effectiveness, safety and tolerance, providing more options for the topical treatment of psoriasis.

The changes of early cognitive function and cerebral hemodynamics in patients with lacunar cerebral infarction / 中国脑血管病杂志

Objective Toinvestigatethechangesofcognitiveimpairmentandcerebralhemodynamics inpatientswithacutelacunarcerebralinfarctionwithin2weeksafteronset.Methods Nineteenpatients with lacunar cerebral infarction (a patient group)were consecutive enrolled in the study. Twenty-three sex-and age-matched inpatients without ischemic cerebrovascular disease or healthy volunteers of outpatient department over the same period were used as a control group. The cerebral hemodynamic features were evaluated with transcranial Doppler (TCD)breath-holding test and single photon emission computed tomography (SPECT)resting + adenosine stress imaging. Simultaneously,the neuropsychological tests were performed,the Montreal cognitive assessment (MoCA)was performed including executive capacity, structural capacity,memory (including auditory memory,visual memory,and logic memory ),information processing speed,and visual-spatial ability. Results (1 )There were no significant differences in the years of education,hypertension,diabetes,hyperlipidemia,coronary heart disease,and smoking between the 2 groups (all P>0. 05). Compared with the control group,there were significant differences in the MoCA score,visual memory,executive function,structural capacity,and information processing speed of the patient group (all P<0. 05). (2)19 patients completed the SPECT resting + load test (12 in the control group and 7 in the patient group). There were significant differences in the uptake ratio (UR)in the right basal ganglia (8. 91[-2. 48 - 5. 87]and -6. 21 [-10. 39 - 5. 42 respectively])and left frontal lobe UR (11. 62 [2. 93-16. 87]and 1. 04 [-10. 17- 3. 82]respectively)between the patient group and the control group (P<0. 05). (3)26 patients completed the breath-holding test + head-up tilt table test (n=13 in each group]. The vascular motor reactivities were 13 ± 5 on the left and 21 ± 7 on the right, and the breath-holding indexes were 0. 66 ± 0. 26 on the left and 1. 0 ± 0. 4 on the right in the patient group;the vascular motor reactivities were 24 ± 11 on the left and 30 ± 9 on the right,and the breath-holding indexes were 1. 21 ± 0. 57 on the left and 1. 5 ± 0. 4 on the right in the control group. There were significant differencesbetweenthe2groups(P<0.05).Conclusion Attheearlystageoflacunarinfarction,the patients have presented varying degrees of cognitive impairment and the changes of cerebral hemodynamics.

Efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>What benefits and toxicities patients acquire from the use of bevacizumab combined with firstline chemotherapy remains controversial. This study was performed to evaluate the efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer (mCRC).</p><p><b>METHODS</b>Several databases, including PubMed, Embase, and Cochrane Library, were searched up to April 30, 2013. Eligible studies were only randomized, controlled trials (RCTs) with a direct comparison between mCRC patients treated with and without bevacizumab. Overall risk ratio (RR), hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed or random-effects models depending on the heterogeneity of the included trials.</p><p><b>RESULTS</b>Six RCTs, including 1582 patients in chemotherapy plus bevacizumab group and 1484 patients in chemotherapyalone group, were included. Overall, the addition of bevacizumab to first-line chemotherapy increased overall response rate (ORR) by 4.5%, prolonged both progression-free survival (PFS) and overall survival (OS), and increased the rate of total Grades 3 or 4 adverse events (G3/4AEs) by 6.9%. Significant differences were found in ORR (RR = 1.22 (95% CI 1.01-1.46), P = 0.03), PFS (HR = 0.60 (95% CI 0.47-0.77), P < 0.0001), OS (HR = 0.83 (95% CI 0.70-0.97), P = 0.02), and any G3/4AEs (OR = 1.56 (95% CI 1.29-1.89), P < 0.00001).</p><p><b>CONCLUSION</b>Bevacizumab is a valuable addition to the current first-line chemotherapy regimens used in patients with mCRC, because of conferring a significant improvement in ORR, PFS, and OS, even though it increased adverse events.</p>

Effects of ileal transposition on non-obese type 2 diabetic rats / 中华普通外科杂志

Objective To evaluate effects and possible mechanisms of ileal transposition on spontaneous non-obese type 2 diabetic GK rats.Methods 20 GK rats were randomly divided into two groups:ileal transposition group and sham operation group (n =10).We observed and determined the weight change,daily average food consumption and FBG (fasting blood-glucose) level of rats before the operation (0 weeks) and 1,4,8,16 and 24 weeks after the surgery.Glucose tolerance test (GTT) was carried out and GLP-1 (glucagon-like peptide-1) concentration measured before the operation (0 weeks) and 4,8,16 and 24 weeks after the surgery and the fasting insulin concentration before the surgery (0 weeks)and 4,24 weeks after the surgery measured,and the indicator of HOMA-IR calculated.Results There was no significant difference in the operating time between the two groups [(87 ± 8) min vs.(84 ± 7)min],P ＞ 0.05.Compared with those before surgery,body weight and food consumption of the two groups of rats decreased significantly a week after surgery (P ＜ 0.05),and then the body weight and food consumption of the two groups of rats all gradually increased,but the difference of the two groups of rats has no statistical significance 1-24 weeks after surgery (P ＞ 0.05).The FBG of the two groups of rats a week after surgery [ileal transposition group (6.1 ± 0.6) mmol/L,sham operation group (6.2 ± 0.8) mmol/L]decreased significantly compared with that before surgery [(7.0 ± 0.5) mmol/L and (6.9 ± 0.5) mmol/L](P ＜ 0.05),and then FBG of the two groups of rats all rose again.The FBG of the rats in surgery group decreased slowly from 8 to 24 weeks after surgery,while the FBG of the rats in the sham surgery group maintained the preoperative level,and the differences of the FBG of the two groups all have statistical significance 8-24 weeks after surgery (P ＜ 0.05).Four weeks after surgery,OGTT of the ileal transposition group significantly improved (P ＜ 0.01).24 weeks after surgery,fasting insulin levels of the ileal transposition group were lower [(0.26 ± 0.08) ng/mL vs.(0.42 ± 0.09) ng/ml],P ＜ 0.05.Compared with the sham surgery group,and HOMA-IR was lower (1.1 ± 0.4) vs.(2.6 ± 0.4),P ＜ 0.05.Four weeks after surgery,oral glucose-stimulated peak (30 min) levels of blood GLP-1 increased markedly in operation groups after surgery (P ＜ 0.01).Conclusions Ileal transposition is effective for the treatment of non-obese T2DM rats,and the control of blood glucose does not depend on the reduction of body weight and food comsumption,and the high secretion of GLP-1 after ileal interposition seem to be helpful in diabetes control.

Tip-to-tip interaction in the crystal packing of PACSIN 2 is important in regulating tubulation activity

The F-BAR domain containing proteins PACSINs are cytoplasmic phosphoproteins involved in various membrane deformations, such as actin reorganization, vesicle transport and microtubule movement. Our previous study shows that all PACSINs are composed of crescent shaped dimers with two wedge loops, and the wedge loop-mediated lateral interaction between neighboring dimers is important for protein packing and tubulation activity. Here, from the crystal packing of PACSIN 2, we observed a tight tip-to-tip interaction, in addition to the wedge loop-mediated lateral interaction. With this tip-to-tip interaction, the whole packing of PACSIN 2 shows a spiral-like assembly with a central hole from the top view. Elimination of this tip-to-tip connection inhibited the tubulation function of PACSIN 2, indicating that tip-to-tip interaction plays an important role in membrane deformation activity. Together with our previous study, we proposed a packing model for the assembly of PACSIN 2 on membrane, where the proteins are connected by tip-to-tip and wedge loop-mediated lateral interactions on the surface of membrane to generate various diameter tubules.

Diagnosis and treatment of Mirizzi syndrome: a single-centre experience / 中华肝胆外科杂志

Objective To study the diagnosis and surgical treatment of Mirizzi syndrome (MS).Method The clinical data of patients with Mirizzi syndrome treated in our center from July 2001 to July 2011 were retrospectively studied and the diagnostic methods,operative strategies and outcomes of surgical treatment were analyzed.Results Mirizzi syndrome (MS) was identified in 56 out of 13800patients who received cholecystectomy (0.4％). MS was diagnosed preoperatively in 30 patients (53.6％).There were 29 patients with Mirizzi syndrome type Ⅰ,17 patients with type Ⅱ,9 patients with type Ⅲ,and 1 patient with type Ⅳ using the Csendes's classification.In two patients (3.6％) coincidental gallbladder carcinoma was detected.An initial laparoscopic approach was attempted in 33patients,and 16 were converted to open surgery.The remaining 23 patients underwent open operation.Surgical procedures included cholecystectomy,choledochotomy and T-tube insertion,simple closure and drainage (via T tube) of the biliary fistula,Roux-en-Y hepaticojejunostomy,radical resection of gallbladder and hepaticojejunostomy.Inadvertent bile duct injury occurred in 2 patients who had an initial laparoscopic approach for a preoperative undiagnosed MS. Postoperative morbidities included biliary leak (n =4) and residual common bile duct stone (n=2).All patients recovered completely and there was no hospital mortality.Conclusions Preoperative diagnosis of Mirizzi syndrome is still challenging despite the availability of multiple imaging modalities.Open surgery remains the standard of care,although laparoscopic treatment may be used in selected patients,especially for type Ⅰ Mirizzi syndrome.Patients with Mirizzi syndrome should be managed differently,basing on intraoperative findings and the type of Mirizzi syndrome.

The diagnosis and surgical treatment of hyperthyroidism complicating thyroid carcinoma / 中华普通外科杂志

Objective To evaluate the diagnosis and surgical treatment of primary hyperthyroidism with concurrent thyroid carcinoma. Methods The clinical data of 43 hyperthyroidism cases complicating thyroid carcinoma, confirmed by pathology at our hospital from January 1999 to September 2010 were retrospectively analyzed. Results Preoperatively 40 patients were examined by ultrasound,29 cases were diagnosed with carcinoma, the diagnostic accuracy of ultrasound was 72. 5%. Thyroidectomy was performed in all the 43 patients, including subtotal thyroidectomy (5 patients), homolateral total thyroidectomy and contralateral subtotal thyroidectomy with neck dissection (25 patients ), total thyroidectomy with neck dissection or radical neck dissection (11 patients ) and lobectomy plus isthmus resection (2 patients ).Postoperative pathology identified papillary carcinoma in 38 cases, and follicular carcinoma in 5 cases.Postoperative temporary hypocalcemia developed in 3 cases and one suffered from irritating when drinking.No hoarseness or blooding. 39 patients were followed-up from 2 to 110 months averaging 45 months, there was no tumor recurrence. Conclusions Preoperative routine ultrasonography helps to identify thyroid carcinoma that coexists with primary hyperthyroidism. The postoperative prognosis of thyroid papillary carcinoma concurrent with hyperthyroidism is satisfactory.

Adherence of Candida albicans to two Denture Base Resins with Different Surface / 中华医院感染学杂志

OBJECTIVE To assess the adherence ability of Candida albicans to two denture base resins with different surface roughness.METHODS In adhesion assays,two denture base resins were made into standard test samples with different surface roughness.Suspension of C.albicans(ATCC 10261) strain was used to adhere on the test samples,and cultured to observe the adhesive effect of a mixed salivary pellicle with Candida to these surfaces.RESULTS In glass surface group,the amount of C.albicans adhering to heat-curing denture base resins was 15.33?2.80,and the amount of C.albicans adhering to Valplast flexible denture resin was 13.67?2.94;In gypsum surface group,the amount of C.albicans adhering to heat-curing denture base resins was 22.67?4.84,and the amount of C.albicans adhering to Valplast flexible denture resin was 21.17?3.31.Significantly greater adhesion of C.albicans to rough surfaces rather than smooth surfaces of the same material was found,at the same time C.albicans had different adhesive ability on different denture base resins(P

Optimization of the Separation and Purification Process of Astragaloside Ⅳ by Orthogonal Experiment / 中国药房

OBJECTIVE:To optimize the technologic conditions for separation and purification process of Astragaloside Ⅳ using macroreticular resins.METHODS:The optimal extraction process and purification technology using macroreticular resins were investigated by orthogonal experiment design with extract yield and content of Astragaloside Ⅳ as evaluation indexes,and the influencing factors were also investigated.RESULTS:The optimal conditions for extraction were as follows:sixfold amount of water was added to extract Astragaloside Ⅳ for 3 times with 1 h each time.The isolation and purification of Astragaloside Ⅳ were influenced by relative density,elution dosage and velocity.CONCLUSION:The established optimal technologic conditions for the extraction,separation and purification of Astragaloside Ⅳ using macroreticular resins proved to be feasible.

Preparation Process and TLC Identification of Rutong Capsules / 中国药房

OBJECTIVE: To establish the preparation process and TLC for Rutong Capsules. METHODS: The preparation process was optimized by orthogonal experiment design. The components in the preparation were identified qualitatively by TLC, and the quality standard of the preparation was established. RESULTS: Radix Angelicae Sinensis, Fructus Aurantii, Radix Bupleuri were able to be identified by TLC, and the physical and chemical characteristics of Poria and Rhizoma Atractylodes macrocephala were able to be identified. CONCLUSION: The method adopted in the study is simple, accurate and reproducible, and it is applicable for the preparation and TLC of Rutong Capsules.

Imaging Diagnosis of Fibrous Dysplasia(A Report of 31 Cases) / 实用放射学杂志

Objective To study the imaging diagnostic methods of fibrous dysplasia.Methods 31 patients with fibrous dysplasia proved pathologically were studied. In addition to CT scan in 11 cases and MRI in 6 cases,plain films were performed in all 31 cases. The compartive analysis was made between the features of plain film and CT.Results Of 31cases, 18 patients had monostotic fibrous dysplasia and 13 polyostotic lesions. Roentgenologically, they were divisible into 4 type: cystic type(18 lesions),diffuse type(30 lesions),sponge groud-flesh type(2 lesions) and moth-eaten type(2 lesions). CT features of lesions were classified into 2 type: cystic expanded type(38 lesions) and osteosclerotic type(7 lesions).Conclusion X-ray film should be used as the first choice in diagnosis of fibrous dysplasia. CT is hightly sensitive in displaying the craniofacial lesions.The lesions can be correctly diagnosed in most instances,if plain film combined with CT.