Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

OBJECTIVE: To investigate the feasibility and prognostic implications of assessing volume status during early fluid resuscitation in septic patients based on estimated plasma volume status (ePVS). METHODS: A prospective study was conducted. Patients with sepsis admitted to intensive care unit (ICU) of the First Affiliated Hospital of Kunming Medical University from March to December in 2023 were enrolled. The general information and laboratory indicators at ICU admission were recorded, and ePVS, sequential organ failure assessment (SOFA) score, acute physiology and chronic health status evaluation II (APACHE II) score were calculated. The vital signs, arterial blood gas analysis and volume status related indicators before liquid resuscitation (T0h) and 3 hours (T3h) and 6 hours (T6h) of fluid resuscitation were recorded. The diameter and variability of the inferior vena cava (IVC) were measured by ultrasound, and ePVS, percentage change value of estimated plasma volume status (ΔePVS%), difference in central venous-to-arterial partial pressure of carbon dioxide (Pcv-aCO₂), and lactate clearance rate (LCR) were calculated. Patients were divided into sepsis group and septic shock group based on the diagnosis at ICU admission, and septic patients were subdivided into survival group and death group based on their 28-day survival status. The differences in clinical data between the groups were compared. The correlation between ePVS or ΔePVS% and volume status related indicators during early liquid resuscitation was analyzed by Spearman rank sum correlation test. The predictive value of each variable for 28-day survival in patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve), and 28-day death risk factors were analyzed by Logistic regression method. RESULTS: Fifty-four septic patients were enrolled in the final analysis, including 17 with sepsis and 37 with septic shock; 34 survived at 28 days and 20 died, with a 28-day survival rate of 63.0%. Compared with the sepsis group, the septic shock group had a lower venous ePVS at ICU admission [dL/g: 4.96 (3.67, 7.15) vs. 7.55 (4.36, 10.07), P < 0.05]. Compared with the death group, the survival group had higher T6h arterial and venous ΔePVS%, and albumin [Alb; T6h arterial ΔePVS% (%): 11.57% (-1.82%, 31.35%) vs. 0.48% (-5.67%, 6.02%), T6h venous ΔePVS%: 9.62% (3.59%, 25.75%) vs. 1.52% (-9.65%, 7.72%), Alb (g/L): 27.57±4.15 vs. 23.77±6.97, all P < 0.05], lower SOFA score, APACHE II score, AST, T0h Lac, and T3h and T6h norepinephrine dosage [SOFA score: 9.00 (8.00, 10.00) vs. 11.50 (9.25, 14.50), APACHE II score: 18.00 (14.75, 21.25) vs. 25.50 (21.00, 30.00), AST (U/L): 34.09 (23.20, 56.64) vs. 79.24 (25.34, 196.59), T0h Lac (mmol/L): 1.75 (1.40, 2.93) vs. 3.25 (2.33, 5.30), norepinephrine dosage (mg): 0.98 (< 0.01, 3.10) vs. 4.60 (1.05, 8.55) at T3h, 1.82 (0.38, 5.30) vs. 8.20 (2.80, 17.73) at T6h, all P < 0.05]. While there were no significantly differences in other basic data and ePVS at all of the time points before and after resuscitation between the two groups. Correlation analysis showed that T6h venous ePVS was significantly positively correlated with T6h IVC variability in septic patients (r = 0.360, P < 0.05), T0h arterial ePVS was significantly negatively correlated with T3h and T6h liquid intake volume (r₁ = -0.367, r₂ = -0.280, both P < 0.05), and venous ePVS at ICU admission was significantly positively correlated with NT-proBNP at ICU admission (r = 0.409, P < 0.05). T6h venous ΔePVS% was significantly positively correlated with T3h liquid intake volume and T6h LCR (r₁ = 0.286, r₂ = 0.286, both P < 0.05), and significantly negatively correlated with T6h urine volume and T6h change value of Pcv-aCO₂ (ΔPcv-aCO₂; r₁ = -0.321, r₂ = -0.371, both P < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of T6h venous ΔePVS% for predicting 28-day survival in septic patients was 0.726 [95% confidence interval (95%CI) was 0.578-0.875, P = 0.006], with a sensitivity of 82.4%, a specificity of 60.0%, and an optimal cut-off value of 3.09%. Binary multifactorial Logistic regression analysis showed that an increase in T6h venous ΔePVS% was a protective factor for 28-day death in patients with sepsis on early fluid resuscitation [odds ratio (OR) = 0.900, 95%CI was 0.834-0.972, P = 0.007]. CONCLUSIONS ePVS may have potential for assessing the volume status of septic patients during early fluid resuscitation. The ΔePVS% during early fluid resuscitation may help to identify septic patients with a poor prognosis.
Humans ; Prognosis ; Fluid Therapy ; Sepsis/physiopathology* ; Prospective Studies ; Plasma Volume ; Intensive Care Units ; Resuscitation ; Male ; Female ; Middle Aged ; Shock, Septic/therapy*

Anti- N-methyl- D-aspartic acid (NMDA) receptor encephalitis is an autoimmune encephalitis mediated by anti-NMDA receptor antibody. At present, the diagnosis of the disease depends mainly on typical clinical symptoms and detection of specific antibodies in cerebrospinal fluid. Early and timely treatment can curb the disease progression and improve the prognosis of the disease. However, because of the atypical clinical manifestations of patients and long waiting time for antibody detection, early identification is difficult. Imaging equipment is more popular in primary hospitals in China, and it is easier to perform imaging examination for suspected patients in the early stage; therefore, this article aims to review the imaging characteristics and current imaging research progress of anti-NMDA receptor encephalitis in recent years, so as to improve clinicians' understanding and early recognition of this disease.

Autoimmune encephalitis (AE) is a novel form of encephalitis associated with antibodies to cell-surface or synaptic proteins. Epileptic seizures act as the predominant manifestation of AE which are triggered by interaction between kinds of antibodies and antigens on cell-surface or intracellular. Patients with AE-related epilepsy are insensitive to antiepileptic drugs but sensitive to immunotherapy. Early initiation of immunotherapy can significantly improve the prognosis. To date, there are few reports on the treatment plan of antiepileptic drug to the patients with AE-related epilepsy. In this review we report the most relevant data about the morbidity, pathogenesis and treatment of AE-related epilepsy with aim of providing better treatment options.

Objective To investigate the efficacy of drug-coated balloon in treatment of femoropopliteal artery occlusive disease.Methods The clinical data of 49 patients with femoropopliteal artery occlusive disease from Feb 2016 to Oct 2017 were retrospectively analyzed.25 cases underwent drugcoated balloon treatment (DCB group),and 24 cases received plain balloon angioplasty (POBA group).Results The procedures were successful in all cases.There were no amputation or death occurred.In DCB group compared to POBA group,the patency rate at postoperative 3 months were not significantly different (96.0％ vs.87.5％,P ＞ 0.05),while it was significantly different at postoperative 6 and 12 months (88.0％ vs.66.7％;80.0％ vs.50.0％,both P ＜0.05).Minimal lumen diameter (MLD) changes and late lumen loss(LLL):The MLD in preoperative,immediate postoperative was not statistically significant between the three group(P ＞ 0.05).At 6 months and 12 months after operation,MLD of DCB group was higher than POBA group (P ＜ 0.05).At 12 months after surgery,LLL in DCB group was significantly lower than the POBA group (P ＜ 0.05).Conclusion DCB is the effective method to treat femoropopliteal artery occlusive disease,which has better short and mid-term efficacy than POBA.

OBJECTIVETo grasp the clinical efficacy of acupuncture in the treatment of primary insomnia (PI), and analyze its future research directions.

METHODSA total of 41 prospective randomized controlled trials (RCTs) were conducted in which the clinical efficacy of acupuncture for treatment of PI was compared with sedative and hypnotic drugs in recent six years by searching databases of CNKI, database, PubMed, and BioMed Central (BMC), the aspects of diagnostic criteria, efficacy standards, observation time, control drugs, characteristics of acupoint selection and regularity were used to review and analyse.

RESULTSAcupuncture treatment for PI was mainly based on acupoints in the head, combined with selecting the points according to the different syndrome, showing short-term efficacy and safety advantages, but it was not well-established in many aspects such as diagnostic criteria, efficacy evaluation, observation time, and control drugs.

CONCLUSIONCurrent evidence shows that acupuncture treatment is effective, but it is necessary to add more stringent RCTs, and introduce objective monitoring indicators to strengthen the evidence and enhance the overall level of research.

Objective To investigate the value of Chlamydia trachomatis antigen in patients with tubal infertility and its effect on the prevention of infection. Methods 80 patients with tubal infertility who were admitted in our hospital from January 2016 to October 2017 were selected as the study group and 80 patients with tubal patency by hysterosalpingography in our hospital were selected as the control group. The study group underwent Chlamydia trachomatis antigen detection. The relevant indicators were observed and clinical diagnostic effect and the effect of infection prevention of patients was recorded in detail. Results The diagnostic results showed that there were 77 cases diagnosed in the study group, and the diagnostic coincidence rate was 96. 2％, of which the diagnostic coincidence rates of tubal blockage, genital tract infection, tubal effusion, acute salpingitis were 100. 0％, 96. 1％, 96. 6％, 93. 8％. The positive rate of Chlamydia trachomatis antigen in the study group was 82. 5％ (66/80). The positive rate of Chlamydia trachomatis antigen in the control group was 15. 0％ (12/80). The positive rate of the study group was significantly higher than that of the control group (P＜0. 05). The test results showed that the incidence of abortion, preterm birth, dead fetus, stillbirth, ectopic pregnancy and other symptoms was significantly higher in the positive patients' study group. In the aspect of infection prevention, the number of patients infected at each time period in the study group gradually reduced with the growth of time and the increase of number of infected people. Conclusion The detection of Chlamydia trachomatis antigen in patients with tubal infertility can achieve high coincidence rate of clinical diagnosis, earlier detection of tubal disease in patients and timely treatment measures, reduce the incidence of postoperative infection in patients, which should be further applied in clinical.

Objective To investigate the effect of ovulation induction of letrozole and clomiphene on the treatment of polycystic ovary syndrome.Methods From February 2014 to February 2014 80 cases with polycystic ovary syndrome in Hangzhou maternity hospitalas the research object were divided into two groups: the control group and the observation group.The control group were treated with clomiphene;the observation group were treated with letrozole.The clinical effect in the two groups were compared.Results The total effective rate was 95.0% in the observation group, which was higher than 67.5% in the control group, the difference was statistically significant(P<0.05).The thickness of endometrium in the observation group was(9.10±1.32)mm and(5.38±0.61)mm in the control group at the HCG injection day, the difference between the two groups was statistically significant (P<0.05).Conclusion Letrozole can be used in the treatment of polycystic ovary syndrome, can get high quality treatment effect, worthy of promotion.

Objective To observe the clinical effect of Guizhi Fuling pill in the treatment of interstitial tubal pregnancy.Methods80 cases with interstitial tubal pregnancy in Hangzhou obstetrics and gynecology hospital from August 2015 to December.2016 were randomly divided into the observation group and the control group, 40 cases in each group.The control group were given methotrexate and mifepristone, at this basis, the observation group were given Guizhi Fuling pill.The effect was analyzed in the two groups.Results①β-HCG negative time in the observation group were significantly shorter than that in the control group(P<0.05).②Adverse reactions rate in the observation group was significantly lower than that in the control group(P<0.05).ConclusionIt can shorten the treatment time, reduce the adverse reaction which Guizhi Fuling pill was used in the adjuvant treatment of interstitial tubal pregnancy.

Objective To evaluate the relationship between amniotic fluid (AF) epidermalgrowth factor (EGF) concentration and fetal pulmonary maturation. Methods Lecithin － sphin-gomyelin ratio (L/S) and EGF were measured in amniotic fluid from women(n = 138,21～42 weeks'gestation) undergoing amniocentesis by TLC and RIA. ResultsThe AF L/S ratio and EGF concen-tration increased linearly with Gestational age(GA) ( r = 0.8t3 and 0.87, respectively, P < 0.01 ).There was a strong correlation between the AF L/S ratio and EGF( r = 0.76, P < 0. 001 ). Conclu-sionThere are a confirmed relationship between AF EGF levels and fetal pulmonary maturation.