Risk Assessment of the Onset of Sleep-related Painful Erection / 中山大学学报(医学科学版)

ObjectiveSleep-related painful erections （SRPE） is a rare sleep disorder characterized by repeated awakening due to painful interruptions of penile erections during nighttime sleep， and its etiology is currently unclear. The purpose of this study is to explore the impact of potential risk factors on the incidence of SRPE. MethodsInformation was collected through questionnaires administered to patients who presented at the urology department and suffered from SRPE or did not suffer from SRPE. A total of 290 participants completed the study， including 145 controls and 145 cases. Logistic regression analysis was used to assess the impact of age， occupation， sleep initiation time per night， frequency of sexual intercourse per week， psychological status， erectile dysfunction， chronic prostatitis， prostate enlargement， lumbar spine disease， central nervous system disease， hypertension， diabetes and family history on the onset of SRPE. ResultsSingle-factor logistic regression analysis found that a history of chronic prostatitis， intellectual labor occupation， central nervous system disease， late sleep onset， frequency of sexual activity， and anxiety status might be related to the onset of SRPE. After incorporating these factors into a multivariate regression analysis model， it was found that having sexual activity ≥2 times/week （OR 95%CI = 0.326（0.179，0.592） and late sleep onset （after 24：00） （OR 95%CI = 0.494（0.265，0.918）might be protective factors for SRPE， while a history of chronic prostatitis（OR 95%CI = 3.779（2.082，6.859） might be a risk factor for SRPE. However， there was no significant statistical difference in the impact of central nervous system diseases and occupation on multivariate analysis. ConclusionChronic prostatitis and anxiety status may be independent risk factors for SRPE； having sexual activity ≥2 times/week and delaying sleep time appropriately may be independent protective factors.

Recent advances in drug screening methods of SARS-CoV-2 spike protein / 药学学报

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

The preliminary therapeutic effect of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in treatment of cirrhotic patients with gastric varices and gastric-renal shunt / 临床肝胆病杂志

ObjectiveTo investigate the safety and efficacy of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in the treatment of cirrhotic patients with gastric varices and gastric-renal shunt （GRS）. MethodsThe patients who attended Beijing Ditan Hospital， Capital Medical University， due to liver cirrhosis and gastric varices from February to June 2023 were enrolled， and all patients were confirmed to have GRS and received endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips. The primary evaluation index was alleviation or disappearance of varicose veins after surgery， and the secondary evaluation indices were surgical completion and complications. ResultsA total of 11 patients were enrolled in this study， among whom there were 7 male patients and 4 female patients， with a median age of 55 years. Of all patients， 1 had Child class A liver function， 7 had Child class B liver function， and 3 had Child class C liver function. The maximum （median） diameter of the shunt was 8 mm， and the minimum （median） diameter of the shunt was 4 mm. The median blood flow velocity of the target vessel was 11 cm/s before treatment and 5 cm/s after occlusion with metal clips. The median amount of tissue adhesive injected was 2 mL， and the amount of lauromacrogol used was 1 mL. Disappearance of blood flow signals was observed in all patients after surgery （100%）， and the success rate of surgery was 100%. No patient experienced rebleeding after follow-up for 6 weeks. Gastroscopy at 1 month after surgery showed that gastric varices were eradicated or almost disappeared in 9 patients and were alleviated in 2 patients. ConclusionEndoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips is a feasible， safe， and effective treatment method for cirrhotic patients with gastric varices and GRS.

Reflections on Social Work Helps to Narrative Medicine Practice in China / 中国医学伦理学

Modern medical model advocates holistic medical treatment and holistic care, which transforms the concern about diseases in traditional medicine into the concern about people in modern medicine. Narrative medicine, as a tool for practicing holistic medical treatment and holistic care, runs through the whole process of patients’ entering medical procedures. It not only meets the needs of patients’ disease-related narratives, but also provides a new and more comprehensive way of communication for both doctors and patients, which is helpful to promote the comprehensive recovery of patients and the healthy development of doctor-patient relationship. At present, narrative medicine is facing some difficulties in the process of local practice in China. Social work, as one of the main bodies of multi-disciplinary and inter-professional cooperation in the medical field, can give full play to its professional advantages to help the new exploration of narrative medicine practice in China.

Passenger lymphocyte syndrome after liver transplantation in a blood group AB recipient with a blood group A donor: a case report / 中国输血杂志

【Objective】 To explore the laboratory monitoring procedure and its clinical significance in patients with passenger lymphocyte syndrome after liver transplantation. 【Methods】 The Hb and bilirubin levels were monitored in one AB blood type patient post-liver transplantation. The ABO blood group type, unexpected antibody screening test, direct anti-globulin test and acid elution test were performed respectively in blood samples of the patient to identify the serum antibodies and erythrocyte membrane sensitized antibodies. 【Results】 The patent’s Hb level showed a decreasing trend on the day 11 post-operation, reaching the lowest level of 62 g/L on day 17, and his serum bilirubin increased. The patient’s ABO blood type was determined as AB while anti-B antibody was detected in the patient’s serum. The direct anti-globulin test was weakly positive, while the unexpected antibody screening test was negative. Anti-B antibody was detected in the elution and the patient’s serum. The patient′s serum was incompatible with type AB and type B erythrocytes in the cross-matching test, while it was compatible with type A and type O erythrocytes. 【Conclusion】 Through monitoring serum anti-A, anti-B and direct anti-human globulin test, the patients with passenger lymphocyte syndrome after liver transplantation can be early diagnosed and the prognosis can be improved.

Severity and multiple indexes of jaundice in ABO hemolytic disease of fetus and newborn: a comparative analysis / 中国输血杂志

【Objective】 To explore the correlation between the severity of jaundice in ABO hemolytic disease of fetus and newborn (HDFN) and multiple indicators, in order to achieve accurate diagnosis, timely treatment, and prevent complications in ABO HDFN. 【Methods】 From March 2020 to February 2023, a total of 283 ABO HDFN in our hospital were classified into mild, moderate and severe groups based on total bilirubin levels. The differences in basic data, relevant laboratory indicators and the agglutination intensity of the three hemolysis tests were analyzed and compared. 【Results】 In the severe group, 75% (12/16) were male infants, which was significantly higher compared to 37.5% (57/152) in the moderate group (P<0.05). The values (mg/dL) of transcutaneous jaundice in the mild, moderate and severe groups were:forehead 9.88±1.93 vs 12.34±2.01 vs 15.56±2.69, face 10.25±2.27 vs 13.28±2.32 vs 15.99±2.86, chest 9.67±2.16 vs 12.51±2.11 vs 15.33±2.36, respectively. The values(µmol/L) of direct bilirubin (DBIL) and indirect bilirubin (IBIL) were 9.87±2.06 vs 11.90±2.59 vs 16.12±4.73, and 159.36±37.55 vs 252.98±30.52 vs 353.76±55.68, respectively, and the differences between the mild, moderate and severe groups were statistically significant (all P<0.05) . The creatine kinase (CK) values(unit/L) of mild, moderate and severe groups were 664.15±498.26 vs 500.51 ±451.63 vs 402.63±224.27, and the difference between the mild group and the other two groups was statistically significant (P<0.05) . There was no statistically significant difference in the agglutination intensity of the three hemolysis tests among HDFN with different severity of jaundice. 【Conclusion】 Clinicians can predict the severity of jaundice in light of gender, transcutaneous jaundice, DBIL, IBIL and CK of ABO HDFN, for further and graded treatment, so as to avoid the sequelae or even life-threatening consequences caused by ABO HDFN.

The effects and mechanisms of trimethylamine-N-oxide on insulin sensitivity in insulin target cells / 药学学报

Gut microbial metabolite trimethylamine-N-oxide (TMAO) is associated with type 2 diabetes (T2DM). Decreased insulin sensitivity is a significant etiological factor of T2DM. Adipocytes, myocytes, and hepatocytes are the three major target cells for insulin. This study aims to investigate the effects and mechanisms of TMAO on the insulin sensitivity of these target cells. Research results indicate that in different ages of db/db diabetic mice, plasma TMAO levels were increased. TMAO significantly inhibits the insulin signaling pathways in these three major insulin target cells, reduces glucose uptake in 3T3-L1 adipocytes and L6 myocytes and downregulates genes related to gluconeogenesis in primary mouse hepatocytes. Furthermore, in mice with normal insulin sensitivity, elevating plasma TMAO levels to those seen in db/db mice using a minipump results in impaired glucose tolerance and hyperinsulinemia. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). Mechanistic studies suggest that TMAO exposure increases the levels of endoplasmic reticulum stress-related proteins in these three major insulin target cells. In summary, TMAO directly attenuates insulin sensitivity in insulin target cells, and its mechanism of action may involve enhancing endoplasmic reticulum stress.

Clinical research progress on drugs for non-alcoholic steatohepatitis treatment / 药学学报

Nonalcoholic steatohepatitis (NASH) is the leading chronic liver disease worldwide. NASH is commonly associated with metabolic risk factors, including obesity, hypertension, and diabetes. Hepatic glucose and lipid metabolism disorder, bile acid toxicity, oxidative stress, inflammation, fibrosis, intestinal dysbacteriosis, and susceptibility gene variation are involved in the pathogenesis of NASH. Drug development for NASH has been slow, this article focuses on the clinical research and development of several promising NASH drugs and their mechanisms, such as drugs targeting gut-liver axis, improving metabolism, inhibiting inflammation and fibrosis.

Evolutionary Law of Syndrome and Syndrome Elements during the Malignant Transformation of Chronic Hepatitis B / 中医杂志

ObjectiveTo clarify the evolutionary laws of syndromes and syndrome elements at different stages during the malignant transformation of chronic hepatitis B （CHB）. MethodsA total of 671 patients with hepatitis B virus infection， who were admitted to the outpatient and inpatient departments of Dongzhimen Hospital of Beijing University of Chinese Medicine and The Fifth Medical Center of Chinese PLA General Hospital from July 1st， 2020 to June 30th， 2021， were included， involving 120 cases of CHB， 340 cases of hepatitis B liver cirrhosis （HBLC）， 64 cases of precancerous lesions with hepatitis B liver cirrhosis （PLHC）， and 147 cases of hepatitis B liver cirrhosis with hepatocellular carcinoma （HCC）. A Survey form of traditional Chinese medicine syndrome during malignant transformation of chronic hepatitis B was designed， and the general information， auxiliary examination and the four examinations results were collected. Factor analysis and K-means clustering were used to determine and statistically analyze the syndrome and syndrome elements. ResultsFive traditional Chinese medicine （TCM） syndrome types were identified in CHB patients， while there were six TCM syndrome types in HBLC， PLHC and HCC stages. Among CHB patients， the main syndromes were liver constraint and spleen deficiency （53.33%） and liver-gallbladder damp-heat （21.67%）， and the dominant syndrome elements were qi stagnation （27.60%）， heat （17.71%） and qi deficiency （17.71%）. In the HBLC stage， the syndromes were mainly blood stasis obstructing the collaterals （23.83%） and liver constraint and spleen deficiency （22.35%）， with dominant syndrome elements being blood stasis （19.25%）， dampness （17.46%）， and qi deficiency （15.01%）. For the PLHC stage， the primary syndrome types were blood stasis obstructing the collaterals （29.68%） and liver-kidney yin deficiency （20.31%）， and the leading syndrome elements were blood stasis （22.12%）， yin deficiency （15.93%）， and qi deficiency （15.04%）. In the HCC stage， the syndrome was dominated by blood stasis obstructing the collaterals （33.34%） and liver-kidney yin deficiency （19.73%）， with the main syndrome elements being blood stasis （24.52%）， yin deficiency （16.09%）， and qi deficiency （15.33%）. During the progression of CHB to malignancy， there was a gradual decrease in excess syndromes including liver-gallbladder damp-heat and water-dampness internal obstruction from 21.67% to 19.04%. In contrast， deficiency syndromes including liver-kidney yin deficiency and spleen-kidney yang deficiency increased from 15.83% to 31.97%. Additionally， excess syndrome elements including qi stagnation， heat and dampness decreased from 59.89% to 34.48%， while deficiency syndrome elements including qi deficiency， yin deficiency and yang deficiency increased from 32.30% to 41.00%. ConclusionDuring the malignant transformation of CHB， there exists a progression of syndrome and syndrome elements， shifting from qi stagnation， heat and qi deficiency to blood stasis （predominantly excess）， dampness and qi deficiency， and then to blood stasis （predominantly deficiency）， yin deficiency and qi deficiency， characterized by “deficiency-excess complex， and shift from excess to deficiency”.

Recent advances in mass spectrometry imaging and its application in drug research / 中国药科大学学报

@#Mass spectrometry imaging (MSI), a label-free molecular imaging technique, has been applied widely in the spatial localization of small molecule metabolites, lipids, peptides, and proteins, with its unique advantage of high spatial resolving power compared to traditional liquid chromatography-mass spectrometry (LC-MS).With the nonstop advancement of its achievable sensitivity and spatial resolution, MSI technique has been providing novel perspectives into the preclinical studies of drugs, such as in vivo localization of drugs and their metabolites, visualization of drug metabolism, and drug delivery tracking.This review introduces the basics of MSI techniques, including basic principles, key features, technical advantages, and limitations, with particular highlight of the recent applications of MSI in drug efficacy and safety evaluation, drug distribution research, drug delivery research, and analysis of Chinese medicine from recent publications, aiming to promote the utilization and further expansion of MSI in the research and development of drugs.

Ginsenoside Rg1 attenuates palmitate-induced HMCs fibrosis by inhibiting NOX4/MAPK pathways / 中国药理学通报

Aim To investigate the inhibitory effect of ginsenoside Rg1 on sodium palmitate induced fibrosis in human glomerullar mesangial cells (HMCs) and its mechanism. Methods (1) HMCs were treated with different concentrations of PA for 24 h, the intracellular lipid accumulation was observed by oil red staining, and the intracellular ROS production was detected by H2DCFDA kit; (2) HMCs were divided into control, PA (160 μmol·L

Baicalin inhibits streptozotocin-induced neuroinflammation in Alzheimer' s disease rat model by TLR4/MyD88/NF-κB pathway / 中国药理学通报

Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg

Research of pharmacokinetics of thalidomide in SD rats with inflammatory bowel disease / 中国药理学通报

Aim To investigate the absorption of thalidomide in inflammatory bowel disease(IBD)SD rats compared with healthy rats to provide a basis for the safety and efficacy of thalidomide in clinical practice. Method The IBD rat model was induced by the 2, 4, 6-trinitrobenzene sulfonic acid, by which the rats were continuously intervened for six days. The general state and disease activity index of the rats were recorded every day. The rats in IBD group after modeling and control group were administered with thalidomide at a dose of 10 mg·kg-1. The blood sample of the rats was collected at different time points. After a comprehensive evaluation of morphological and histopathological results, the samples of rats with IBD were determined by proven high performance liquid chromatography-mass spectrometry,and the pharmacokinetic parameters were calculated and compared with the healthy rats. Results The body weight of rats in IBD group was obviously lower than that in control group and the disease activity index, score of colonic macroscopic morphous and histopathology were obviously higher than those in control group. The success rate of modeling was 62.5%. The pharmacokinetic results showed that the Cmax(P<0.05)and AUC(P<0.01)of the IBD group both increased by 2 to 3 times, but there was no significant difference in t1/2,Tmax,MRT and other parameters. Conclusions The rate and extent of oral thalidomide absorption of rats in the model of inflammatory bowel disease significantly increase compared to those of healthy rats, which may provide new considerations for clinical practice of thalidomide in the treatment of IBD.

Analysis of 9 cases of pediatric-type follicular lymphoma / 中华儿科杂志

Objective: To summarize the pathological diagnosis, clinical features, treatment methods and outcomes of pediatric-type follicular lymphoma (PTFL). Methods: Clinical data including the pathology, clinical features, treatment methods, and follow-up results of 9 PTFL patients admitted to Henan Cancer Hospital from February 2017 to February 2023 were analyzed retrospectively. Results: The age of onset in 9 children was 6 to 18 years, all the patients were males. The clinical manifestation was local painless lymph node enlargement in the head and neck, with a stage of Ⅰ-Ⅱ. The histomorphological characteristics of PTFL were similar to those of classic follicular lymphoma (FL). The germinal center of most follicles were enlarged, the mantle zone disappeared, centroblasts were easily visible, and the histological grade were mostly grade Ⅲ, which may be accompanied by the "starry sky" phenomenon. Monoclonal peaks can be seen in B cell clonal rearrangements (BCR). Immunohistochemistry (IHC) showed CD20 positive, CD10 positive, Bcl-6 positive, Bcl-2 negative, C-myc negative, and Ki-67 was 70%-95%. Fluorescence in situ hybridization (FISH) test was negative for t (14, 18), Bcl-2 translocation, and C-myc translocation. Six cases underwent surgical resection, and 3 cases underwent surgical resection combined with chemotherapy. Up to February 2023, with a follow-up time of 45 to 72 months, all children survived without any recurrence and were in a complete remission state. Conclusions: PTFL is mainly characterized by adolescent male onset, with early clinical manifestations and pathological manifestations of high-level histological status, high proliferation index, and lack of t (14; 18)/Bcl-2 translocation and Bcl-2 expression. It is mainly treated by localized surgical excision and has a good prognosis.

Clinical analysis of 86 cases of acute fatty liver of pregnancy / 中华妇产科杂志

Objective: To investigate the clinical characteristics and maternal and fetal prognosis of pregnant women with acute fatty liver of pregnancy (AFLP). Methods: The clinical data of 86 AFLP pregnant women admitted to the Third Affiliated Hospital of Guangzhou Medical University from September 2017 to August 2022 were collected, and their general data, clinical characteristics, laboratory tests and maternal and fetal outcomes were retrospectively analyzed. Results: (1) General information: the age of the 86 pregnant women with AFLP was (30.8±5.4) years, and the body mass index was (21.0±2.5) kg/m2. There were 50 primiparas (58.1%, 50/86) and 36 multiparas (41.9%, 36/86). There were 64 singleton pregnancies (74.4%, 64/86) and 22 twin pregnancies (25.6%, 22/86). (2) Clinical characteristics: the main complaints of AFLP pregnant women were gastrointestinal symptoms, including epigastric pain (68.6%, 59/86), nausea (47.7%, 41/86), anorexia (46.5%, 40/86), vomiting (39.5%, 34/86). The main non-gastrointestinal symptoms were jaundice of skin and/or scleral (54.7%, 47/86), edema (38.4%, 33/86), fatigue (19.8%, 17/86), bleeding tendency (16.3%, 14/86), polydipsia or polyuria (14.0%, 12/86), skin itching (8.1%, 7/86), and 17.4% (15/86) AFLP pregnant women had no obvious symptoms. (3) Laboratory tests: the incidence of liver and kidney dysfunction and abnormal coagulation function in AFLP pregnant women was high, and the levels of blood ammonia, lactate dehydrogenase and lactic acid were increased, and the levels of hemoglobin, platelet and albumin decreased. However, only 24 cases (27.9%, 24/86) of AFLP pregnant women showed fatty liver by imageology examination. (4) Pregnancy outcomes: ① AFLP pregnant women had a high incidence of pregnancy complications, mainly including renal insufficiency (95.3%, 82/86), preterm birth (46.5%, 40/86), hypertensive disorders in pregnancy (30.2%, 26/86), gestational diabetes mellitus (36.0%, 31/86), fetal distress (24.4%, 21/86), pulmonary infection (23.3%, 20/86), disseminated intravascular coagulation (16.3%, 14/86), multiple organ dysfunction syndrome (16.3%, 14/86), hepatic encephalopathy (9.3%, 8/86), and intrauterine fetal death (2.3%, 2/86). ② Treatment and outcome of AFLP pregnant women: the intensive care unit transfer rate of AFLP pregnant women was 66.3% (57/86). 82 cases were improved and discharged after treatment, 2 cases were transferred to other hospitals for follow-up treatment, and 2 cases (2.3%, 2/86) died. ③ Neonatal outcomes: except for 2 cases of intrauterine death, a total of 106 neonates were delivered, including 39 cases (36.8%, 39/106) of neonatal asphyxia, 63 cases (59.4%, 63/106) of neonatal intensive care unit admission, and 3 cases (2.8%, 3/106) of neonatal death. Conclusions: AFLP is a severe obstetric complication, which is harmful to mother and fetus. In the process of clinical diagnosis and treatment, attention should be paid to the clinical manifestations and laboratory tests of pregnant women, early diagnosis and active treatment, so as to improve maternal and fetal outcomes.

Efficacy and safety analysis of the zanubrutinib-based bridging regimen in chimeric antigen receptor T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.

A high-throughput Gaussia luciferase reporter assay for screening potential gasdermin E activators against pancreatic cancer

It is discovered that activated caspase-3 tends to induce apoptosis in gasdermin E (GSDME)-deficient cells, but pyroptosis in GSDME-sufficient cells. The high GSDME expression and apoptosis resistance of pancreatic ductal adenocarcinoma (PDAC) cells shed light on another attractive strategy for PDAC treatment by promoting pyroptosis. Here we report a hGLuc-hGSDME-PCA system for high-throughput screening of potential GSDME activators against PDAC. This screening system neatly quantifies the oligomerization of GSDME-N to characterize whether pyroptosis occurs under the stimulation of chemotherapy drugs. Based on this system, ponatinib and perifosine are screened out from the FDA-approved anti-cancer drug library containing 106 compounds. Concretely, they exhibit the most potent luminescent activity and cause drastic pyroptosis in PDAC cells. Further, we demonstrate that perifosine suppresses pancreatic cancer by promoting pyroptosis via caspase-3/GSDME pathway both in vitro and in vivo. Collectively, this study reveals the great significance of hGLuc-hGSDME-PCA in identifying compounds triggering GSDME-dependent pyroptosis and developing promising therapeutic agents for PDAC.

Functional annotation map of natural compounds in traditional Chinese medicines library: TCMs with myocardial protection as a case

The chemical complexity of traditional Chinese medicines (TCMs) makes the active and functional annotation of natural compounds challenging. Herein, we developed the TCMs-Compounds Functional Annotation platform (TCMs-CFA) for large-scale predicting active compounds with potential mechanisms from TCM complex system, without isolating and activity testing every single compound one by one. The platform was established based on the integration of TCMs knowledge base, chemome profiling, and high-content imaging. It mainly included: (1) selection of herbal drugs of target based on TCMs knowledge base; (2) chemome profiling of TCMs extract library by LC‒MS; (3) cytological profiling of TCMs extract library by high-content cell-based imaging; (4) active compounds discovery by combining each mass signal and multi-parametric cell phenotypes; (5) construction of functional annotation map for predicting the potential mechanisms of lead compounds. In this stud TCMs with myocardial protection were applied as a case study, and validated for the feasibility and utility of the platform. Seven frequently used herbal drugs (Ginseng, etc.) were screened from 100,000 TCMs formulas for myocardial protection and subsequently prepared as a library of 700 extracts. By using TCMs-CFA platform, 81 lead compounds, including 10 novel bioactive ones, were quickly identified by correlating 8089 mass signals with 170,100 cytological parameters from an extract library. The TCMs-CFA platform described a new evidence-led tool for the rapid discovery process by data mining strategies, which is valuable for novel lead compounds from TCMs. All computations are done through Python and are publicly available on GitHub.

Value of contrast-enhanced percutaneous ultrasound in the diagnosis of rotator cuff tear subtype / 中国骨伤

OBJECTIVE@#To explore characteristics of contrast-enhanced ultrasound (CEUS) images features and diagnostic value of rotator cuff tear subtypes.@*METHODS@#From January 2019 to March 2022, percutaneous ultrasound-guided subacromial bursography (PUSB) with persutaneous ultrasound-guide tendon lesionography (PUTL) was performed on 114 patients with suspected rotator cuff injury were evaluated, including 54 males and 60 females ranged in age from 35 to 75 years old with an average of (58.8±8.7 ) years old;76 patients on the right side and 38 patients on the left side;the course of disease ranged from 0.13 to 111 months with an average of (10.2±9.8) months. GE LOGIQ E9 color doppler ultrasound diagnostic high frequency(6 to 12 MHz) was used to CEUS Using arthroscopy as gold standard, receiver operating characteristic (ROC) curve was used to evaluate diagnostic efficacy of US, MRI and CEUS for rotator cuff injury, also sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated.@*RESULTS@#The sensitivity of US in diagnosing full-thickness tears was 72.1%, specificity was 93.0%, and accuracy was 85.1%. The sensitivity, specificity and accuracy of MRI diagnosis of full-thickness tear were 90.9%, 92.6% and 92.1% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of full-thickness tear were 100%. The sensitivity, specificity and accuracy of US in the diagnosis of partial tear were 85.7%, 77.2% and 79.8% respectively. The sensitivity, specificity and accuracy of MRI diagnosis of partial tear were 83.7%, 81.7% and 82.5% respectively. The sensitivity, specificity and accuracy of CEUS in diagnosis of partial tear were 95.7%, 92.6% and 93.9% respectively. There were significant differences in diagnosis results of US, MRI and CEUS for rotator cuff bursa tear (P<0.001). Kapp test showed good consistency between CEUS and arthroscopy in diagnosing rotator cuff tear subtypes (full-thickness and partial tears).@*CONCLUSION@#Using PUSB/PUTL to observe distribution of contrast media in bursa, tendon and joint cavity to evaluate the type of rotator cuff tear, its diagnostic performance is significantly better than US and MRI. Therefore, percutaneous contrast-enhanced ultrasound can be a reliable method for diagnosing subtypes of rotator cuff tears.

A Rare Case of Lung Adenocarcinoma with EGFR L833V/H835L Co-mutation and Literature Review / 中国肺癌杂志

Epidermal growth factor receptor (EGFR) mutations are the most common driver genes in the development of non-small cell lung cancer (NSCLC), of which mutations in exons 18-21 are frequent, especially the loss of exon 19 and exon 21 L858R mutation are the most frequent. Other rare gene mutations are rare. Simultaneous occurrence of two or more rare EGFR mutations are extremely rare in lung cancer, and the incidence of EGFR L833V/H835L rare gene compound mutations is very low, and there is little clinical data and evidence of relevant treatment methods. Some EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are effective in treating lung cancer patients with rare gene mutations. In this article, we reported a case of NSCLC patient with a rare gene compound mutation EGFR L833V/H835L, who responded to Afatinib in combination with Anilotinib treatment well after 5 months of treatment, and computed tomography (CT) showed shrinkage of lung lesions. Meanwhile, we also compiled previously reported NSCLC patients with EGFR L833V/H835L rare gene compound mutation and summarized the characteristics of this group of patients and the effect of applying different kinds of EGFR-TKIs treatment.
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