Human immunodeficiency virus type 1(HIV-1)latent reservoirs pose the primary obstacle to curing acquired immunodeficiency syndrome(AIDS).Transactivator(Tat),a regulatory protein encoded by HIV-1,influences the establishment and reactivation of latent reservoirs by promoting viral transcription.Inhibitors targeting Tat protein suppress viral rebound by reducing Tat protein levels and disrupting its transcription-promoting functions.Among the two strategies for treating HIV-1 latent reservoirs,the"block-and-lock"strategy,which is based on Tat protein inhibitors,aims to target HIV-1 proteins or host factors while interfering with histone epigenetic modifications,thereby permanently silencing proviral DNA and maintaining HIV-1 latency even after treatment discontinuation.Tat-related inhibitors such as didehydrocortistatin A(dCA),triptolide,and apalutamide-derived Q308 regulate HIV-1 latency through distinct mechanisms.This review summarizes the regulatory roles of Tat in HIV-1 latency,Tat protein inhibitor-based therapeutic strategies for targeting latent reservoirs,and the mechanisms of action of related inhibitors,with the goal of providing insights for the development of drugs toward achieving functional HIV-1 cure.

Objective:To investigate the clinical efficacy of 3D printed metal augment or tibial prosthesis for reconstruction of large bone defects in total knee arthroplasty (TKA) and knee revision surgery.Methods:A total of 7 patients (7 knees) with TKA or knee revision who were admitted to the Department of Orthopaedics of the Second Affiliated Hospital of Zhejiang University School of Medicine with large bone defects from July 2018 to December 2023 were retrospectively analyzed, including 4 patients with TKA and 3 patients with knee revision. There were 3 males and 4 females, aged 58.7±7.6 years (range, 54-68 years), 3 patients with left knee and 4 patients with right knee. All the patients had bone defects in the knee joint (AORI type III), 2 cases had bone defects only in the femur, 4 cases had bone defects only in the tibia, and 1 case had bone defects in both the tibia and femur, which were treated with personalized reconstruction using 3D printing. Hip-knee-ankle angles, American Knee Society score (KSS) before and after surgery were compared, and postoperative complications were observed.Results:All patients successfully completed the operation, and the operation time was 189.3±35.5 min (range, 125-240 min). Complex TKA was performed in 4 cases with surgical times of 175, 195, 210, and 240 min, and revision surgery was performed in 3 cases with surgical times of 125, 180, and 200 min, respectively. Intraoperative blood loss was 114±24.4 ml (range, 100-150 ml). Five cases used 3D printed metal augment, and two used 3D printed one-piece tibial components. All patients were followed up for 2, 2, 5, 6, 7, 20, 57 months, respectively. The KSS of the five patients at 3 months postoperatively were 56, 61, 66, 56, and 56 points, respectively, greater than the preoperative scores of 35, 44, 36, 27, and 41 points. The KSS functional scores of the five patients at 3 months postoperatively were 45, 45, 45, 30, and 45 points, respectively, which were greater than the preoperative scores of 30, 30, 15, 20, and 20 points. The hip-knee-ankle angle was 181.8°±3.4° (range, 177.9° to 188.0°) at the final follow-up and 175.8°±12.4° (range, 153.3° to 192.1°) before surgery, with no significant difference ( t=-1.230, P=0.242). At the final follow-up, the 3D printed component was well integrated with the bone surface, the prosthesis was securely positioned, and the force lines of the lower limbs were normal. There were no postoperative complications such as poor wound healing, infection, fat liquefaction, nerve injury, deep vein thrombosis of lower limbs, knee joint stiffness, periprosthesis infection and loosening. Conclusion:Using 3D printed metal augment or tibial prosthesis to reconstruct the huge bone defect in TKA and revision has a satisfactory early clinical effect, satisfactory joint function and good surgical safety.

Deficiency, stasis, water and toxin are of great significance in the pathogenesis and pathologic evolution of chronic heart failure (CHF). Based on "deficiency, blood stasis, water and toxin", the pathogenesis and treatment of CHF were discussed in this article. It was found that in the pathogenesis, deficiency--deficiency of heart qi and deficiency of heart yang were the origin of the disease, and blood stasis, water and toxin were the markers of the disease. Among them, blood stasis was the central pathological link, and also an important mechanism that could aggravate the disease and cause a vicious cycle; water-phlegm and water dampness were the basic pathological products; toxin-heat toxin, water toxin, and stasis toxin were the final results of disease progress and product accumulation. In terms of treatment, CHF can be divided into four stages: early, middle, late and end. In the early stage, tonifying qi and regulating heart can be used for the treatment of root cause, and promoting blood circulation and water can be used for the treatment of symptoms; tonifying qi and yin and reinforcing the healthy qi, reducing blood stasis, purging turbid, and eliminating pathogenic factors can be used in the middle stage; reducing blood stasis and removing toxic materials should be used in the late stage, supplemented with warming yang and increasing urine excretion; astringing yang,generating body fluids, tonifying qi and yang should be used in the end stage. At the same time of treating by stages, attention should be paid to adhering to a holistic concept and dialectical treatment; pay attention to timing and flexible medication; adopting a combination of Chinese and Western approaches and integrating them.

Objective:To observe the effect of escitalopram combined with repetitive transcranial magnetic stimulation (rTMS) on efficacy and attention function in patients with first-episode unipolar depression.Methods:Fifty-two first-episode initial-naive unipolar depression patients were enrolled in Department of Neurology of Guangzhou First People's Hospital from March 2022 to April 2023 were chosen. They were randomly allocated to active stimulation group ( n=27) and sham stimulation group ( n=25); both were treated with escitalopram, and active treatment or sham treatment in the left dorsolateral prefrontal cortex (DLPFC) were given for 4 weeks (5 d per week, 20 d totally). Before treatment and 2 and 4 weeks after treatment, Hamilton Depression Rating Scale (HAMD)-24 was used to evaluate depressive symptoms, and Birmingham Cognitive Screening Scale-Chinese (BCoS-C) was used to evaluate the attention function. Results:(1) In terms of depressive symptoms: HAMD-24 scores of the active stimulation group 2 and 4 weeks after treatment (20.63±2.73, 15.85±2.43) were significantly lower than those before treatment (25.74±2.68, P<0.05); HAMD-24 scores of sham stimulation group 4 weeks after treatment were also significantly lower than those before treatment ([20.48±2.33] vs. [25.80±2.57], P<0.05); HAMD-24 scores of the active stimulation group 2 and 4 weeks after treatment were significantly lower than those of sham stimulation group ( P<0.05). (2) In terms of auditory attention indicators: total correct number (selective attention) in active stimulation group 4 weeks after treatment was significantly larger than that before treatment (51.74±1.38 vs. 47.48±1.60), and the sustained index (sustained attention) was significantly lower than that before treatment (0.74±0.71 vs. 4.37±1.15, P<0.05); total correct number in active stimulation group 4 weeks after treatment was significantly larger than that in sham stimulation group (48.00±1.66), and the sustained index was significantly lower than that in sham stimulation group (3.72±1.28, P<0.05). Conclusion:Combined with escitalopram, rTMS can more effectively mitigate the depressive symptoms in first-episode unipolar depression patients, and depressive symptoms improve more quickly than attentional function.

Hemodynamics is a branch of fluid mechanics, which mainly studies the physiological process of circulatory system from the perspective of mechanics, and has a wide range of applications in medicine. The entity teaching model is made to help medical students master the knowledge of hemodynamics more easily and intuitively by showing them the phenomenon of laminar flow, turbulence and axial concentration of red blood cells. And then we check their learning effect by questionnaires. Students are interested in the entity teaching model that the teacher has used in the class. Thus, the entity teaching model can play an important role in the teaching process.

Objective: To investigate the short-term outcome of patients with acute myocardial infarction complicating cardiogenic shock due to left main disease. Methods: A total of 24 patients with acute myocardial infarction complicating cardiogenic shock due to left main artery disease hospitalized in Fuwai hospital from June 2012 to May 2018 were included. The clinical data were analyzed,and the patients were divided into survivor group (11 cases) and death group (13 cases) according to survival status at 28 days post the diagnosis of shock. The patients were further divided into thrombolysis in myocardial infarction(TIMI) flow grade 0-2 group (11 cases) and TIMI flow grade 3 group (13 cases) according to TIMI flow grade after the procedure. The patients were then divided into non-three-vessel lesions group (14 cases) and three-vessel lesions group (10 cases) according to coronary angiography results. Results: Compared with survivor group, patients in death group presented with lower worst systolic blood pressure within 24 hours after admission (50(48, 70) mmHg (1 mmHg=0.133 kPa) vs. 73(70, 80) mmHg, P<0.01), lower worst diastolic blood pressure with in 24 hours after admission ((33.5±12.4) mmHg vs. (48.9±9.4) mmHg, P<0.01), higher respiratory rates ((27.3±2.5) times/min vs. (21.5±4.0) times/min, P<0.01), less 24 hours urine output ((422±266) ml vs. (1 680±863) ml, P<0.01), lower platelet counts ((161.9±81.9)×10⁹/L vs. (241.6±94.0)×10⁹/L, P=0.03), higher serum creatinine ((250.0±36.8) μmol/L vs. (132.7±34.2) μmol/L, P<0.01), higher alanine aminotransferase (288(76,846) IU/ml vs. 81(42, 109) IU/ml, P=0.04), lower artery pH (7.11±0.17 vs. 7.39±0.09, P<0.01), higher lactic acid ((10.29±3.62) mmol/L vs. (4.21±2.85) mmol/L, P<0.01), higher incidence of invasive ventilation (7/13 vs. 2/11, P=0.02), higher scores of acute physiology and chronic health evaluation (APACHE) Ⅱ (35.4±6.8 vs. 18.7±1.7, P<0.01) and simplified acute physiology score (SAPS) Ⅱ (73.5±17.4 vs. 47.0±4.3, P<0.01), and higher incidence of target vessel TIMI flow grade 0-2 (10/13 vs. 1/11, P<0.01). Kaplan-Meier survival curve analysis showed that survival rate at 28 days post the diagnosis of shock in TIMI flow grade 3 group was higher than that in TIMI flow grade 0-2 group (76.9% vs. 9.1%, log-rank test, P<0.01), and mortality rate was similar at 28 days post the diagnosis of shock between non-three-vessel lesions group and three-vessel lesions group (35.7% vs. 60.0%, log-rank test, P=0.14). Multivariate logistic regression analysis showed that compared with TIMI flow grade 0-2 group, the OR value of death at 28 days post the diagnosis of shock in TIMI flow grade 3 patients with acute myocardial infarction complicating cardiogenic shock due to left main disease was 0.030(95%CI 0.003-0.340, P<0.01). Conclusion Short-term outcomeof patients with acute myocardial infarction complicating cardiogenic shock due to left main disease remains poor, and final flow of TIMI grade 3 is confirmed as independent protective factor of death at 28 days post the diagnosis of shock in these patients.

Objective To observe the functional connectivity of attentional network in first-episode treatment-naive depressed patients with resting-state functional MR imaging (rfMRI),and to investigate the neuropathologic mechanism of attention dysfunction.Methods Eighteen first-episode treatment-naive depressed patients were collected in our hospital from August 2015 to March 2017,and 16 healthy controls matched with age,gender and education were chosen at the same time period.All subjects accepted rfMRI.Pearson correlation analysis was performed on all the time series values of the two regions of interest (ROIs),and their correlation coefficient was obtained.Fisher z transformation was performed to reflect the functional connection strength of the two ROIs through z scores.Results As compared with healthy controls,depressed patients showed abnormal enhancement on functional connectivity of the attentional network in the left anterior cingulate and supplementary motor area (z scores:0.21 ±0.10 vs.0.13±0.09,P=0.029),right basal ganglia region and dorsolateral prefrontal cortex (z scores:0.18±0.12 vs.0.10±0.08,P=0.048),right frontal eye field and intraparietal suleus (z scores:0.19± 0.12 vs.0.10±0.05,P=0.006),right frontal eye field and nucleus ceruleus (z scores:0.18±0.13 vs.0.09± 0.07,P=0.018).Conclusion Abnormal functional connectivity of attentional network exists extensively in first-episode treatment-naive depressed patients,which may be due to attention impairment in depressed patients.

Objective To analyze and research the Chinese medicine of tonifying kidney recipe on the mechanism of recurrent spontaneous abortion IL-4, IFN-gamma cytokine.Methods60 patients in accordance with the inclusion criteria with recurrent miscarriage from January 2013 to December 2015 were selected, according to the random number table method, the patients were randomly divided into Chinese medicine group, Western medicine group,Combine traditional Chinese and western medicine group, Chinese medicine group treated with traditional Chinese medicine of tonifying kidney recipe, Western Medicine group were given intramuscular injection of progesterone injection,combining traditional Chinese and Western medicine group was treated with acupuncture combined with progesterone Chinese medicine.The course of treatment was 15 days, before and after treatment in patients with pregnancy outcome and IL-4, IFN-gamma levels.ResultsThere was no significant difference between the three groups before treatment with IL-4 and IFN-.After treatment,compared with the traditional Chinese and Western medicine group, western medicine group, Chinese medicine group of IL-4, IFN-, respectively, showed a rise and fall, the difference was statistically significant(P<0.05).After treatment, compared with the traditional Chinese medicine group, the IL-4 and IFN-of the western medicine group were increased and decreased, respectively, and the difference was statistically significant (P<0.05).Combination of traditional Chinese and Western medicine to obtain a higher clinical cure rate.ConclusionThe combination of TCM and Western medicine for improving the efficacy of pregnancy outcome of recurrent spontaneous abortion and exact expression may obviously improve the IL-4 and IFN-gamma, help to improve the IL-4, reduce the expression of IFN-gamma, improve the outcome of pregnancy.

Objective To investigate the effect of endovascular treatment to initial and long-term outcomes of postpartum deep venous thrombosis (DVT) . Methods The clinical data, venography and 3-yaer follow up data of 30 female patients with acute or subacute deep vein thrombosis in the postpartum period who received endovascular therapy consisting of catheter-directed thrombolysis with angioplasty (stenting for some patients with iliac vein compression syndrome (IVCS)) were retrospectively evaluated. Clot removal was graded as grade Ⅲ(>95%), grade Ⅱ(50% to 95%), and grade Ⅰ(<50%). Grade Ⅱ, Ⅲconsidered effective. Data from onset time, vaginal delivery or by elective, patients ages, IVCS or not and stenting or not were included in this analysis. And the χ2 test and survival analysis was used for statistical analysis of initial and long-term patency respectively. Results In 30 cases, the initial result included 14 cases(46.7%) of gradeⅢ, 12 cases(40.0%) of gradeⅡand 4 cases(13.3%) of gradeⅠ. Patients' onset time, vaginal delivery or by elective, patients ages and IVCS or not have no significant statistical difference to initial patency(χ2=0.88, 1.28, 1.15, 3.08,P>0.05).For 18 patients with IVCS, there was significant statistical difference between patients implanting stents(initial patency was 100.0%(7/7) and whom not
implanting stents(initial patency was 63.6%,7/11) (χ2=5.14, P<0.05). 1, 3, 6 months and 1, 2, 3 years follow-up showed: The primary patency of postoperative 1, 3, 6 months respectively were 86.7%, 70%(21/30),66.7%(20/30), and postoperative 1, 2, 3 years were all 66.7%. There was significant statistical difference between patients with IVCS implanting stents and whom not implanting stents (χ2=6.562, P<0.05), patients with IVCS not implanting stents and whom without IVCS (χ2=3.377, P<0.05). There was no significant statistical difference among patients with IVCS implanting stents and whom without IVCS(χ2=1.932, P>0.05). Conclusions Endovascular therapy consisting of catheter-directed thrombolysis with angioplasty could be considered as a primary therapeutic procedure in patients with acute or subacute postpartum DVT. Stenting for treatment of iliac compression which contributed to postpartum DVT is very valuable to ensuring higher long-term patency rate.