ObjectiveTo investigate the effect of Tongxinluo capsules on the use of anti-ischemic drugs in patients with chronic coronary syndrome （CCS） of Qi deficiency and blood stasis. MethodA multicenter，prospective cohort study was conducted，with Tongxinluo capsules intervention as the exposure factor. Patients were divided into an exposed group （combination of traditional Chinese and western medicine） and a non-exposed group （western medicine alone），and followed up for one year. The use of anti-ischemic drugs was observed on the day of enrollment and at 3，6，12 months. ResultA total of 186 patients were enrolled，with 128 in the exposed group and 58 in the non-exposed group. There were no statistically significant differences in baseline characteristics between the two groups. At the 3-month follow-up，the types of first-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01），and this difference remained statistically significant at 6 months （P<0.05） but was no longer significant at 12 months. At the 3- and 6-month follow-ups，there were no significant differences between the two groups in the types of second-line anti-ischemic drugs used. However，at the 12-month follow-up，the types of second-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01）. At the 3-month follow-up，both groups showed a reduction in the types of first-line anti-ischemic drugs used compared to baseline （P<0.05），with a more pronounced reduction in the exposed group （P<0.05）. At the 6-month follow-up，the exposed group showed a significant reduction in the types of second-line anti-ischemic drugs used compared to baseline （P<0.05），while no significant changes were observed in the non-exposed group. At the 12-month follow-up，the difference in the types of second-line anti-ischemic drugs between the exposed and non-exposed groups was statistically significant （P<0.05），while there was no significant difference in the types of first-line anti-ischemic drugs. ConclusionTongxinluo capsules can effectively reduce the use of anti-ischemic drugs in patients with CCS of Qi deficiency and blood stasis.

Objective To investigate the effect of microglial derived extracellular vesicles on neuronal damage in the context of heat stress.Methods After BV2 microglial cells were exposed to heat stress,the supernatant was collected and subjected to ultracentrifugation at different speeds to obtain large and small vesicles,respectively.Nano Particle Tracking and Zeta Potential Distribution Analyzer was used to measure and analyze the size distribution of the large vesicles and small vesicles.Western blotting was used to detect the expression of specific vesicle surface markers,TSG101,CD63 and flotillin-1.Microglial extracellular vesicles were labeled with PKH67 dye and then co-cultured with N2a cells to examine the uptake by capacity the neurons.After large and small vesicles derived from microglia after heat stress stimulation were co-cultured with N2a cells,respectively,CCK-8 assay,lactate dehydrogenase (LDH)assay,Trypan blue staining and TUNEL assay were employed to evaluate heat stress induced neuronal damage.Results The small vesicles were in a particle size of 30～120 nm,and highly expressed TSG101 and CD63,whereas the large vesicles,in a size of 90～1000 nm,highly expressed flotillin-1.The BV2-derived extracellular vesicles could be taken up by N2a cells and were proved to be involved in the modulation of N2a cell injury caused by heat stress.CCK-8 assay showed that both large and small vesicles of microglial cells inhibited the viability of N2a cells after heat exposure (P<0.05).The results of LDH assay,Trypan blue staining and TUNEL assay showed that both large (P<0.05)and small vesicles (P<0.01)significantly enhanced the LDH release,blue stain intensity and apoptosis of N2a cells after heat exposure,and the release,intensity and apoptosis were stronger in the cells treated with small vesicles than those group of large vesicles.Conclusion Microglia aggravate heat stress-induced neuronal damage through releasing extracellular vesicles.

OBJECTIVE: To investigate how the National Health Commission of China (NHCC)-recommended Chinese medicines (CMs) modulate the major maladjustments of coronavirus disease 2019 (COVID-19), particularly the clinically observed complications and comorbidities. METHODS: By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology (hyperinflammations, viral replication), complications (pain, headache) and comorbidities (hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search. RESULTS: Overall, 9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8 and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively. CONCLUSION The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.
COVID-19/physiopathology* ; Comorbidity ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine ; Medicine, Chinese Traditional ; SARS-CoV-2

Objective:To evaluate the effect of driving pressure (ΔP)-guided PEEP titration on lung injury in elderly patients undergoing robot-assisted radical prostatectomy (RARP).Methods:Forty-six American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients, aged 65-80 yr, with body mass index of 19-28 kg/m 2, with Assess Respiratory Risk in Surgical Patients in Catalonia score assessed as medium to high risk, scheduled for elective RARP, were divided into control group (group C, n=23) and ΔP titration group (group D, n=23) using a random number table method.Volume-controlled mechanical ventilation was used after anesthesia induction and tracheal intubation.In group C, 5 cmH 2O was used to fix PEEP.In group D, the optimal PEEP was titrated after computer-controlled breathing and after establishing Trendelenburg position and pneumoperitoneum, the first titration started from 4 cmH 2O and increased by 1 cmH 2O every 4 min until ΔP reached the minimum value or PEEP increased to 12 cmH 2O, and the second titration was increased in increments as the method described above based on the optimal PEEP of the first titration.At 4 min after completion of the first PEEP titration (T 1, 4 min after mechanical ventilation with fixed PEEP in group C), 2 h after establishment of Trendelenburg position (T 2), 1 min after extubation (T 3) and 2 h after operation (T 4), serum concentrations of Clara cell protein (CC16), surfactant protein D (SP-D), soluble receptor for advanced glycation end-products (sRAGE) and soluble intercellular adhesion molecule-1 (sICAM-1). Pulmonary complications were assessed within 7 days after operation. Results:The serum concentrations of CC16, SP-D, sRAGE and sICAM-1 were significantly higher at T 2-4 than at T 1 in two groups ( P<0.05). Compared with group C, the serum concentrations of CC16, SP-D, sRAGE and sICAM-1 were significantly decreased at T 2-4 ( P<0.05), and no significant change was found in the incidence of pulmonary complications within 7 days after operation in group D ( P>0.05). Conclusions:ΔP-guided PEEP titration can reduce lung injury in elderly patients undergoing RARP.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC

Objective:To evaluate the effect of driving pressure-guided individualized positive end-expiratory pressure (PEEP) titration on atelectasis in elderly patients undergoing robot-assisted radical prostatectomy.Methods:Fifty elderly patients, aged 65-80 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with body mass index of 19-28 kg/m 2, undergoing elective robot-assisted radical prostatectomy under general anesthesia, were divided into 2 groups ( n=25 each) according to the random number table method: traditional lung-protective ventilation group (group C) and driving pressure-guided individualized PEEP group (group D). The method for setting PEEP was as follows: PEEP 5 cmH 2O was used throughout operation in group C. In group D, the optimal PEEP was titrated after intubation and mechanical ventilation and Trendelenburg position-pneumoperitoneum construction, the initial value was the lowest PEEP allowed by the anesthesia machine, the PEEP was increased by 1 cmH 2O (PEEP≤12 cmH 2O) every 4 min, the plateau pressure and PEEP were simultaneously recorded to calculate the driving pressure, and the corresponding PEEP was considered as the optimal PEEP for the individual when the driving pressure reached the minimum.Ultrasound examination was performed after catheterization of radial artery (T 0), after anesthesia induction (T 1), 4 min after developing optimal PEEP ventilation (T 2, 4 min after developing ventilation in group C), after restoration of body position (T 3), before extubation (T 4), and at 2 h after admission to postanesthesia care unit (T 5). Atelectatic aeration loss scores were recorded at T 0, T 1, T 4 and T 5.Bilateral optic nerve sheath diameter was measured at T 0-4.Arterial blood gas analysis was performed at T 0, T 2, T 3 and T 5, PaO 2 and PaCO 2 were recorded, and oxygenation index was calculated.The postoperative pulmonary complications within 3 days after operation were recorded. Results:Compared with group C, atelectasis aeration loss scores at T 4, 5 and PaCO 2 at T 2, 3 were significantly decreased, and PaO 2 and oxygenation index were increased at T 2, 3, 5 in group D ( P<0.05). There were no significant differences in the bilateral optic nerve sheath diameter and incidence of postoperative pulmonary complications between the two groups ( P>0.05). Conclusion:Driving pressure-guided individualized PEEP can increase intraoperative oxygenation and decrease the development of atelectasis in elderly patients undergoing robot-assisted radical prostatectomy.

Objective To evaluate the effect of dynamic lung compliance ( Cydn)-guided positive end-expiratory pressure (PEEP) titration on lung injury in the patients undergoing robot-assisted radical prostatectomy. Methods Forty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients, aged 65-80 yr, with body mass index of 19-28 kg∕m2 , scheduled for elective robot-assisted radical prosta-tectomy under general anesthesia, were divided into 2 groups ( n=20 each) using a random number table method: control group (group C) and PEEP group (group P). Mechanical ventilation was performed ac-cording to preset parameters after tracheal intubation in group C, and PEEP was set by a double titration method after tracheal intubation and after pneumoperitoneum in group P. At 4 min after intubation (T1), 4 min, 1 h and 2 h after establishing pneumoperitoneum-Trendelenburg position ( T2-4 ) , and 1 and 30 min after extubation ( T5,6 ) in group C or at 4 min after completing the first PEEP titration ( T1 ) , 4 min, 1 h and 2 h after completing the second PEEP titration (T2-4) and T5,6 in group P, blood samples were collect-ed from the radial artery for determination of club cell protein 16, surfactant protein-D, tumor necrosis fac-tor-alpha and interleukin-6 concentrations in serum ( by enzyme-linked immunosorbent assay) . Results Compared with group C, the serum concentrations of club cell protein 16 at T2-6 and surfactant protein-D, tumor necrosis factor-alpha and interleukin-6 at T3-6 were significantly decreased in group P (P<0. 05). Conclusion Cydn-guided PEEP titration can reduce the lung injury in patients undergoing robot-assisted radical prostatectomy.

Objective To evaluate the effect of dynamic lung compliance ( Cdyn) -guided positive end-expiratory pressure (PEEP) titration on extravascular lung water in elderly patients undergoing robot-assisted radical prostatectomy. Methods Forty American Society of Anesthesiologists physical statusⅡ orⅢ patients, aged 65-80 yr, with body mass index of 19-28 kg∕m2 , scheduled for elective robot-assisted radical prostatectomy, were divided into 2 groups ( n=20 each) using a random number table method:control group (group C) and PEEP group (group P). In group P, immediately after endotracheal intuba-tion, immediately after establishing pneumoperitoneum-Trendelenburg position and after restoring the supine position, PEEP was set starting from the lowest PEEP allowed by the machine, increasing by 2 cmH2 O ev-ery 4 min until the maximum Cdyn was obtained. PEEP was not set in group C. Immediately after establis-hing the invasive blood pressure monitoring ( T1 ) , at 10 min after the first successful PEEP titration ( T2 ) , 10 min, 1 h and 2 h after the second successful PEEP titration ( T3-5 ) , 10 min after the third successful PEEP titration (T6), and 30 min after tracheal extubation (T7) in group P, or at T1, 10 min after intu-bation ( T2 ) , 10 min, 1 h and 2 h after establishing pneumoperitoneum-Trendelenburg position ( T3-5 ) , 10 min after restoring the supine position ( T6 ) and T7 in group C, blood samples were collected from the radial artery for blood gas analysis, and the oxygenation index was calculated. The B-line score was recor-ded at T1 and T7 . Results Compared with group C, the B-line score was significantly decreased at T7 , and the oxygenation index was increased at T5-7 in group P (P<0. 05). Conclusion Cdyn-guided PEEP titration can decrease the formation of extravascular lung water in elderly patients undergoing robot-assisted radical prostatectomy.

Objective To investigate the effect and the mechanism of nifedipine on oxidative stress trip-ping by iron-overload of HK-2 cells. Methods The cells were divided into 4 groups,blank group,iron overload group,nifedipine group and FAC with nifedipine co-treatment group. Cells were treated with FAC or/and nifedipine for 24 hours,and then malonaldehyde (MDA) content,superoxide dismutase (T-SOD) activity,glutathione (GSH) content,intracellular iron content and expression of DMT1 and FPN1 protein were evaluated. Results Compared to the iron overload group,both nifedipine treatment and co-treatment decreased the content of MDA (P < 0.05),increased the activity of SOD(P < 0.05),increased the content of GSH(P < 0.05),reduced the intracellular iron content(P<0.05),increased the expression of DMT1(P<0.05),and increased the expression of FPN1(P < 0.05). Conclusion Nifedipine plays a protective role against oxidative stress induced by iron-overload in HK-2 cells,and it is related to promote DMT1 and FPN1 protein expression and reduce intracellular iron content.

Objective To investigate the effect of parthenolide ( PTL) and PKC inhibitor on human gastrointestinal stromal tumor (GIST) cell proliferation and apoptosis and the mechanism involved .Methods Human GIST cell lines were cultured in vitro, and the cell proliferation rate of GIST , was determinate by MTT;flow cytometry was used to test the early apoptosis rate of GIST;Western blot assay was applied to detect the expression of endoplasmic reticulum stress-related proteins , GRP78 and GADD153.There were four groups: control group , PTL group, PKC inhibitor group , combine PTL and PKC inhibitor group .Results PTL and PKC inhibitor combination therapy for GIST was sig-nificantly more effective than a single-drug therapy (P<0.05);as for the early apoptosis rate , the combination ther-apy for GIST cells was significantly higher than that medication alone group (P<0.05).the expression of endoplas-mic reticulum stress-associated protein GRP 78 and GADD153 was obviously higher in PTL and PKC inhibitor combi-nation group than that in medication alone group (P<0.05).Conclusions PTL and PKC inhibitor combination therapy for GIST cells can induce apoptosis , which is possibly mediated via endoplasmic reticulum stress pathway .