ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective:To evaluate the safety and effectiveness of robot-assisted coronary artery bypass(RACAB).Methods:We retrospectively analyzed the clinical outcomes from 252 consecutive patients who underwent RACAB in our center between April 2021 and August 2023. The internal mammary artery(IMA) was harvested using the skeletonized technique with the assistance of the robotic system. Then, graft-to-target vessel anastomoses were performed via a 4-6 cm left fifth intercostal thoracotomy. Coronary angiography or coronary CTA was routinely performed before discharge.Results:149 patients(59.1%) underwent multi-vessel coronary bypass. 140 patients(55.6%) underwent total arterial bypass grafting, with 131 patients(52.0%) undergoing RACAB with in situ bilateral IMA. IMA harvesting failed in 6 patients(1.6%). One patient(0.4%) was assisted by extracorporeal circulation, and 5 patients(2.0%) underwent re-thoracotomy postoperatively. The patency rate of grafts was 96.6%(449/465). The 12-month and 24-month survival rate were 97.8% and 96.5% respectively; The 12-month and 24-month MACCE-free survival rate were 95.2% and 92.6%, respectively.Conclusion:RACAB is safe and feasible. With the assistance of the robotic system, in situ bilateral IMA can be obtained and bypassed to all target vessels territory. Extended follow-up is warranted.

Objective:To analyze the safety and efficacy of multi-vessel minimally invasive cardiac surgery-coronary artery bypass graft(MICS-CABG) through perioperative angiography results and complications.Methods:Clinical data of 1 073 patients who underwent multi-vessel MICS-CABG surgery at Peking University Third Hospital from December 2015 to June 2024 were collected using an ambispective cohort study. Among them, 745 were males(69.4%), with a median age of 65 years(58, 71), and a median ejection fraction of 0.66(0.56, 0.71). Double-vessel or triple-vessel lesions accounted for 932 cases(86.9%), while left main lesions were present in 449 cases(41.8%). The primary outcome was the evaluation of graft patency based on perioperative angiography or coronary artery computed tomography angiography results, while major cardiovascular adverse events during the perioperative period, surgical complications, and other surgical information were secondary outcomes. The clinical efficacy of multi-vessel MICS-CABG was evaluated.Results:In this study, the median number of grafts was 3, and complete revascularization was performed in 1 006 cases(93.8%); total arterial revascularization was performed in 308 cases(28.6%). Perioperative mortality was 11 cases(1.0%), and the main adverse cardiovascular and cerebrovascular events(MACCE) was 50 cases(4.8%). Three cases(0.3%) had poor wound healing, and 79 patients(7.4%) required transfusion. Postoperative coronary angiography was performed in 907 patients(84.5%) and coronary CTA was performed in 52 patients(4.8%), for an overall review rate of 89.4%(959/1073). The overall patency rate of the bridge vessel was 96.9%, and the patency rate of the left internal mammary artery was 98.2%.Conclusion:Multi-vessel MICS-CABG demonstrates excellent perioperative safety and is capable of achieving complete revascularization for the 3 regions of the heart. The quality of the anastomosis and the postoperative patency rate of the grafts is satisfactory.

Objective:To evaluate the safety and effectiveness of robot-assisted coronary artery bypass(RACAB).Methods:We retrospectively analyzed the clinical outcomes from 252 consecutive patients who underwent RACAB in our center between April 2021 and August 2023. The internal mammary artery(IMA) was harvested using the skeletonized technique with the assistance of the robotic system. Then, graft-to-target vessel anastomoses were performed via a 4-6 cm left fifth intercostal thoracotomy. Coronary angiography or coronary CTA was routinely performed before discharge.Results:149 patients(59.1%) underwent multi-vessel coronary bypass. 140 patients(55.6%) underwent total arterial bypass grafting, with 131 patients(52.0%) undergoing RACAB with in situ bilateral IMA. IMA harvesting failed in 6 patients(1.6%). One patient(0.4%) was assisted by extracorporeal circulation, and 5 patients(2.0%) underwent re-thoracotomy postoperatively. The patency rate of grafts was 96.6%(449/465). The 12-month and 24-month survival rate were 97.8% and 96.5% respectively; The 12-month and 24-month MACCE-free survival rate were 95.2% and 92.6%, respectively.Conclusion:RACAB is safe and feasible. With the assistance of the robotic system, in situ bilateral IMA can be obtained and bypassed to all target vessels territory. Extended follow-up is warranted.

Objective:To analyze the safety and efficacy of multi-vessel minimally invasive cardiac surgery-coronary artery bypass graft(MICS-CABG) through perioperative angiography results and complications.Methods:Clinical data of 1 073 patients who underwent multi-vessel MICS-CABG surgery at Peking University Third Hospital from December 2015 to June 2024 were collected using an ambispective cohort study. Among them, 745 were males(69.4%), with a median age of 65 years(58, 71), and a median ejection fraction of 0.66(0.56, 0.71). Double-vessel or triple-vessel lesions accounted for 932 cases(86.9%), while left main lesions were present in 449 cases(41.8%). The primary outcome was the evaluation of graft patency based on perioperative angiography or coronary artery computed tomography angiography results, while major cardiovascular adverse events during the perioperative period, surgical complications, and other surgical information were secondary outcomes. The clinical efficacy of multi-vessel MICS-CABG was evaluated.Results:In this study, the median number of grafts was 3, and complete revascularization was performed in 1 006 cases(93.8%); total arterial revascularization was performed in 308 cases(28.6%). Perioperative mortality was 11 cases(1.0%), and the main adverse cardiovascular and cerebrovascular events(MACCE) was 50 cases(4.8%). Three cases(0.3%) had poor wound healing, and 79 patients(7.4%) required transfusion. Postoperative coronary angiography was performed in 907 patients(84.5%) and coronary CTA was performed in 52 patients(4.8%), for an overall review rate of 89.4%(959/1073). The overall patency rate of the bridge vessel was 96.9%, and the patency rate of the left internal mammary artery was 98.2%.Conclusion:Multi-vessel MICS-CABG demonstrates excellent perioperative safety and is capable of achieving complete revascularization for the 3 regions of the heart. The quality of the anastomosis and the postoperative patency rate of the grafts is satisfactory.

Objective:To investigate the effects of emodin on lipopolysaccharide(LPS)induced pyroptosis of human dental pulp fibro-blasts(HDPFs)by regulating the high mobility group protein B1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway.Methods:HDPFs were in vitro cultured and grouped into control(normal culture),LPS with low,medium and high dose emodin groups,pcDNA(transfected with pcDNA3.1)and pcDNA-HMGB1 groups(transfected with pcDNA3.1 HMMGB1).qRT-PCR was applied to detect the expression level of HMGB1 mRNA in cells,MTT assay,plate cloning assay and flow cytometry were applied to detect cell prolifera-tion and pyrotosis,respectively.ELISA was applied to detect levels of IL-18,IL-1β and TNF-α in cell supernatant.Western blot was applied to detect the expression of pyroptosis protein Nod-like receptor protein 3(NLRP3),cleaved caspase-1,GSDMD,HMGB1 and TLR4 proteins in the cells.Results:Compared with the control group,the HMGB1 mRNA level,pyrotosis rate,IL-18,IL-1β,TNF-α levels,NLRP3,cleaved Caspase-1,GSDMD,HMGB1,TLR4 protein levels in the LPS group obviously increased,the A490 value and colony formation obviously decreased(P＜0.05).Compared with the LPS group,the above indicators in the low,medium,and high dose emodin groups decreased,the A490 value and colony formation increased,the high-dose emodin group showed more obvious changes(P＜0.05);overexpression of HMGB1 attenuated the inhibitory effects of emodin on LPS-induced pyroptosis and inflammation of HDPFs,and promoted cell proliferation(P＜0.05).Conclusion:Emodin inhibit the activation of NLRP3 inflammasome by inhibiting the HMGB1/TLR4 pathway,thereby reduces LPS induced pyroptosis of HDPFs.

Based on the theory of "one qi circulation" founded by HUANG Yuanyu， the core disease mechanism of colorectal cancer is the innate spleen deficiency and stomach qi failing to bear downward， which leads to the turbidity assemble in large intestine， forming the carcinoma toxin， and ultimately transforms into colorectal cancer. The treatment should base on recovering the circulation of qi， Huangya Decoction （黄芽汤） as the basic formula， the circulation of qi ascending and descending as the base， adjusting ascending and descending together with Xiaqi Decoction （下气汤）， and differentiating the syndrome on yin-yang excess-deficiency； for spleen-kidney yang deficiency syndrome， treated with Tianhun Decoction （天魂汤） to supplement liver， kidney and assist yang； for liver-kidney yin deficiency syndrome， treated wtih Dipo Decoction （地魄汤） to supplement lung， kidney， and assist yang. They jointly prompt one qi circulation to provide the thoughts for the treatment of colorectal cancer by traditional Chinese medicine.

Objective:To discuss the inhibitory effect of Schisandrin B on the proliferation of pancreatic cancer Pan02 cells,and to clarify the mechanism.Methods:CCK-8 method was used to detect the proliferation rates of the Pan02 cells after treated with different concentrations(0,0.78,1.56,3.12,6.25,12.50,and 25.00 mg·L-1)of Schisandrin B to select the optimal concentration and treatment time of Schisandrin B.The mouse pancreatic cancer Pan02 cells were divided into control group(0 mg·L-1 Schisandrin B),2.5 mg·L-1 Schisandrin B group,5.0 mg·L-1 Schisandrin B group,and 10.0 mg·L-1 Schisandrin B group.The morpholoy of Pan02 cells invarious groups was observed with light microscope;5-ethynyl-2'-deoxyuridine(EdU)staining assay was used to detect the positive expression rates of the Pan02 cells in various groups;flow cytometry was used to detect the percentages of the Pan02 cells at different cell cycles and the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of cell cycle and apoptosis-related proteins in the cells in various groups.Results:The CCK-8 method results showed that after treated with Schisandrin B for 48 and 72 h,compared with 0 mg·L-1 Schisandrin B,the proliferation rates of the Pan02 cells after treated with different concentrations of Schisandrin B were decreased(P<0.01),especially at 72 h.0.25,5.0,and 10.0 mg·L-1 Schisandrin B were selected to treat the Pan02 cells,and 72 h was the treatment time.In control group,the Pan02 cells had a spindle shape,with good condition,and grew closely adhered to the wall with normal organelles and cytoplasm,in 2.5 and 5.0 mg·L-1 Schisandrin B groups,the cell volume was decreased,the intercellular adhesion was disappeared,and the cell membrane was intact but more permeable;the cytoplasm shrank and vacuolar structures appeared inside the cells,with some fragmented and floating on the surface of the solution;in 10.0 mg·L-1 Schisandrin B group,the Pan02 cells exhibited notable apoptotic bodies,indicating an apoptotic state.The EdU staining results showed that compared with control group,the rates of EdU positive cells in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly decreased(P<0.01).The flow cytometry results showed that compared with control group,the percentages of the cells at S phase in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01),while the percentages of the cells at G2/M phase were significantly decreased(P<0.01),and the percentages of the cells at G0/G1 phase in 5.0 amd 1.0 mg·L-1 Schisandrin groups were decreased(P<0.01);compared with control group,the apoptotic rates of the cells in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of p27,B-cell lymphoma 2(Bcl-2)associated X protein(Bax),cleaved cysteine aspartic acid protease-3(cleaved Caspase-3),and cleaved poly adenosine diphosphate(ADP)ribose polymerase(cleaved PARP)proteins in the cells in 2.5 mg·L-1 Schisandrin B group were significantly increased(P<0.05 or P<0.01),the expression levels of cyclin A2,cyclin E2,and Bcl-2 proteins in the cells in 5.0 and 10.0 mg·L-1 Schisandrin B groups were significantly decreased(P<0.05 or P<0.01),while the expression levels of p27,Bax,cleaved Caspase-3,and cleaved PARP proteins in the cells in 5.0 and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01).Conclusion:Schisandrin B has an inhibitory effect on proliferation of the pancreatic cancer Pan02 cells,and its mechanism may be related to the activation of the cysteine aspartic acid protease-3(Caspase-3)pathway to induce the apoptosis and activating p27 protein to induce the arrest of cell cycle at S phase.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.