3CL protease (3CLpro) of SARS-CoV-2 is a pivotal enzyme required in coronavirus replication and transcription. Its highly conserved structure and the absence of homologous proteins in the host make it an ideal target for broad-spectrum anti-coronavirus drug development. In this work, we systematically investigated and compared the binding modes and dynamic properties of the four stereoisomers of a pyridyl-urea diyne ester (PyDU) molecule with two chiral centers within the 3CLpro active site. Through molecular docking, MD simulations, MM/GBSA binding free-energy calculations, and DCCM analysis, all four stereoisomers were stabilized primarily by hydrophobic packing. Among them, the (R,S) isomer exhibited the best overall performance, including docking score, binding free-energy components, and key residue interactions. The (R,S) and (S,R) isomers also enhanced the cooperative motions around the binding pocket, while the (R,S) isomer further modulated the flexibility of domain III, which may influence 3CLpro dimerization. Conversely, the (S,S) isomer exhibited the weakest affinity due to insufficient hydrophobic contact. By innovatively integrating chirality, binding energy and protein dynamical features, we revealed the dual role of chirality in modulating affinity and dynamic responses, which provides a theoretical basis for the chiral-guided design of coronavirus inhibitors.

Objective:To explore the effect of scalp electroacupuncture (EA) on central pain sensitization in rats with knee osteoarthritis (KOA).Methods:Thirty-two 8-week-old female Sprague-Dawley rats were randomly divided into a blank control group, a model group, an electroacupuncture (EA) group and a sham EA group, each of 8. All of the rats except those in the control group had KOA induced through intra-articular monosodium iodoacetate injections in the right knee. Two weeks later the EA group rats began receiving daily head EA sessions 6 days/week for 2 weeks. The sham EA group received identical but non-therapeutic stimulation. The blank control and model groups received no EA intervention. Before the modelling and 3, 7, 14, 21 and 28 days later, all of the rats completed bipedal balance pain tests and mechanical allodynia evaluations. After the testing on day 28, all of the rats were euthanized for molecular analyses. Western blotting and immunohistochemistry were performed to examine protein expression of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), and cannabinoid receptor type 1 (CB1R) in both the periaqueductal gray (PAG) matter and spinal dorsal horns (SDHs). Serum levels of substance P (SP) and 5-hydroxytryptamine (5-HT) were also quantified using enzyme-linked immunosorbent assays.Results:Three days after successful modeling, the average weight-bearing capacity of the right hind limb in the model, sham EA and EA groups was significantly lower than that of the blank controls. It reached its lowest level on the 14th day after modeling. Concurrently, the pain responses in those three groups were significantly higher than among the controls, also peaking on the 14th day after modeling. After two weeks of electroacupuncture, the electroacupuncture group showed significant improvement in both right hind limb weight-bearing capacity and pain response compared to the model group. Meanwhile, the levels of BDNF and TrkB protein in the periaqueductal gray matter were significantly higher in the model group than among the blank controls, while the electroacupuncture group exhibited significantly reduced expression of BDNF and TrkB proteins compared to the model group, along with significantly increased CB1R protein expression. The model group showed significantly elevated expression of both BDNF and TrkB proteins in the spinal dorsal horn compared to the blank control group, while there were significant differences between the EA and model groups in the expression of BDNF, TrkB and CB1R proteins. Immunohistochemical analysis on day 28 revealed that the EA group had significantly fewer BDNF- and TrkB-positive cells in the PAG compared to the model group, with significantly more CB1R-positive cells. In the SDH, the model group exhibited significantly increased numbers of BDNF- and TrkB-positive cells compared to the blank control group, whereas significant differences were found between the EA and blank control groups in the numbers of BDNF-, TrkB- and CB1R-positive cells. Serum analysis on day 28 demonstrated that substance P and 5-hydroxytryptamine levels in the model, sham EA and EA groups were significantly higher than in the blank control group, on average. However, no significant differences were observed in serum SP and 5-HT levels between the EA and model groups.Conclusions:Scalp EA significantly alleviates central pain sensitization in KOA, at least in rats, potentially by suppressing BDNF and TrkB expression while upregulating CB1R expression in the PAG matter and the SDH.

Psychotropic medication plays a crucial role in the field of mental illness,and the issues of drug efficacy and safety due to individual differences cannot be ignored.Genetic factors,especially the genetic poly-morphisms related to drug-metabolizing enzymes,drug action targets,and risk,have a significant impact on drug responses.Pharmacogenomics,by detecting genetic polymorphisms,can reveal a patient's inherited tend-encies towards drug efficacy,pharmacokinetic characteristics,and potential toxicity,thereby predicting the therapeutic effects and adverse reactions of drug treatment,and providing guidance for personalized therapy.Therefore,individualized medication based on pharmacogenomics helps to improve cure rates,reduce relapse rates,and decrease medical costs,which is of great significance to clinical medication in mental illness.

Objective:To explore the effect of scalp electroacupuncture (EA) on central pain sensitization in rats with knee osteoarthritis (KOA).Methods:Thirty-two 8-week-old female Sprague-Dawley rats were randomly divided into a blank control group, a model group, an electroacupuncture (EA) group and a sham EA group, each of 8. All of the rats except those in the control group had KOA induced through intra-articular monosodium iodoacetate injections in the right knee. Two weeks later the EA group rats began receiving daily head EA sessions 6 days/week for 2 weeks. The sham EA group received identical but non-therapeutic stimulation. The blank control and model groups received no EA intervention. Before the modelling and 3, 7, 14, 21 and 28 days later, all of the rats completed bipedal balance pain tests and mechanical allodynia evaluations. After the testing on day 28, all of the rats were euthanized for molecular analyses. Western blotting and immunohistochemistry were performed to examine protein expression of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), and cannabinoid receptor type 1 (CB1R) in both the periaqueductal gray (PAG) matter and spinal dorsal horns (SDHs). Serum levels of substance P (SP) and 5-hydroxytryptamine (5-HT) were also quantified using enzyme-linked immunosorbent assays.Results:Three days after successful modeling, the average weight-bearing capacity of the right hind limb in the model, sham EA and EA groups was significantly lower than that of the blank controls. It reached its lowest level on the 14th day after modeling. Concurrently, the pain responses in those three groups were significantly higher than among the controls, also peaking on the 14th day after modeling. After two weeks of electroacupuncture, the electroacupuncture group showed significant improvement in both right hind limb weight-bearing capacity and pain response compared to the model group. Meanwhile, the levels of BDNF and TrkB protein in the periaqueductal gray matter were significantly higher in the model group than among the blank controls, while the electroacupuncture group exhibited significantly reduced expression of BDNF and TrkB proteins compared to the model group, along with significantly increased CB1R protein expression. The model group showed significantly elevated expression of both BDNF and TrkB proteins in the spinal dorsal horn compared to the blank control group, while there were significant differences between the EA and model groups in the expression of BDNF, TrkB and CB1R proteins. Immunohistochemical analysis on day 28 revealed that the EA group had significantly fewer BDNF- and TrkB-positive cells in the PAG compared to the model group, with significantly more CB1R-positive cells. In the SDH, the model group exhibited significantly increased numbers of BDNF- and TrkB-positive cells compared to the blank control group, whereas significant differences were found between the EA and blank control groups in the numbers of BDNF-, TrkB- and CB1R-positive cells. Serum analysis on day 28 demonstrated that substance P and 5-hydroxytryptamine levels in the model, sham EA and EA groups were significantly higher than in the blank control group, on average. However, no significant differences were observed in serum SP and 5-HT levels between the EA and model groups.Conclusions:Scalp EA significantly alleviates central pain sensitization in KOA, at least in rats, potentially by suppressing BDNF and TrkB expression while upregulating CB1R expression in the PAG matter and the SDH.

Objective:To further understand the clinical characteristics of scirrhous gastric cancer (SGC)and clear it definitions. Analyzed the clinicopathologic features and prognosis of patients with SGC and Non SGC(NSGC).Methods:The study included 342 gastric cancer patients who had undergone gastrectomy in the Second Hospital University of South China between May 2011 and May 2018. The SGC was diagnosed by endoscopic, CT, tumor stroma ratio and appearance of surgical specimen clinicopathological characteristics were summarized and compared between SGC patients and NSGC using pearson′s χ2 test or student′s t test. Survival curves were estimated with the Kaplan-Meier method. Patients were matched 1∶1 using propensity score matching, and their overall survival rates were compared. Results:A total of 342 patients with gastrectomy were collected, 49 (14.3%) were diagnosed as SGC. Patients with SGC were younger, later pathological stage lymph node metastases tend to occur than those(NSGC). SGC had a higher total gastric resection rate, easier prone to nerve/vascular invasion and omental metastasis ( P<0.01). The median survival of SGC patients and overall survival at 1, 3, and 5 years after surgery were shorter than NSGC patients, which were independent risk factors affecting the prognosis of patients. Conclusions:SGC can be well defined by endoscopy, CT, TSR and tumor appearance. It is a peculiar solid tumor with poor differentiated, advanced stage and poor prognosis. Future research should focus on how to diagnose SGC earlier and intervene in time.

Perforated peptic ulcer is a common acute abdominal disease and requires emergency surgical treatment. Laparoscopic repair PPU was started early but progressed slowly. Compared with the popularization of minimally invasive concept of laparoscopic cholecystectomy, laparoscopic repair is still under the situation of disputation, low overall application rate and extremely unbalanced development in different regions and organizations. With the embodiment of minimally invasive advantages of laparoscopy and the technology progress, as well as the updating of surgeons′ ideas and the emergence of higher quality RCT studies, the proportion of PPU in laparoscopic treatment is gradually increasing. In order to make full use of the minimally invasive value and differential diagnostic value of laparoscopy, the laparoscopy-first approach can be adopted as a routine for appropriate PPU patients. The key to case selection and the physicians experience and proficiency. Laparoscopy should be actively adopted but should not be easily expanded. If necessary, the patients should be converted to open operation. If not the advantages of laparoscopy will be drowned.

Objective:To analyze the genetic characteristics of Brucella strains isolated from a human brucellosis epidemic in Baoding City of Hebei Province, and to provide scientific basis for control and prevention of brucellosis. Methods:Brucella antibody was detected in a high-risk population ( n=22) of brucellosis in Baoding City in 2018 by using rose bengal plate test and tube agglutination test. Blood samples of patients with brucellosis were collected for Brucella isolation ( n=3). Conventional methods were used to identify the bacteria strains. Multiple locus variable-number tandem repeat analysis (MLVA) and multilocus sequence typing (MLST) were used to analyze the genetic characteristics of the strains. Results:The sero-prevalence of Brucella antibodies in high-risk populations was 4.55% (1/22). Three suspected Brucella strains were isolated from blood samples of three patients (No. BDY-1, BDY-2 and BDY-3) and were identified as Brucella melitensis biovar 3. The results of MLVA showed that strain BDY-1 and strain BDY-2 were the same genotype. Strain BDY-3 added two tandem repeats at the locus of Bruce04 and Bruce16, respectively, and lost three tandem repeats at the locus of Bruce30. The genotype of panel 1 (MLVA-8) and panel 1 + panel 2A (MLVA-11) were 42 and 116, respectively, which belonged to the "East Mediterranean group". They were closely clustered with Brucella melitensis biovar 3. MLST analysis showed that all isolated strains could be classified into a ST8 type. Conclusions:The isolated strains from the epidemic are Brucella melitensis biovar 3. In the future, the prevention and control of brucellosis in Baoding City should strengthen the health education and behavior intervention of the high-risk population.

Objective:To investigate the therapeutic effect of nicorandil on patients with coronary heart disease after interventional therapy, and its influence on serum matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and vascular endothelial function.Methods:From January 2018 to December 2019, 120 patients with coronary heart disease who underwent percutaneous coronary intervention(PCI) were selected from Jinhua People's Hospital.They were divided into control group (60 cases) and observation group (60 cases) according the random digital table method.The control group received rosuvastatin on the second day after PCI, and the observation group received nicorandil on the second day after PCI.The course of treatment in both two groups was 12 weeks.The treatment effects, cardiac function, MMP-9, VEGF and vascular endothelial function were compared between the two groups before and after treatment.Results:The total effective rate of the observation group[93.33%(56/60)] was higher than that of the control group[75.00%(45/60)](χ 2=7.566, P<0.05). After treatment, the LVEF [(46.97±1.78)%] of the observation group was higher than that of the control group [(43.83±2.19)%], while the LVEDD [(56.14±2.37)mm] and LVESD [(47.83±2.69)mm] of the observation group were lower than those of the control group [(61.08±2.96)mm and (52.37±2.73)mm], and the difference was statistically significant between the two groups( t=8.618, 10.091, 9.176, all P<0.05). The levels of MMP-9 [(2.36±0.43)μg/L] and VEGF [(45.26±6.89)ng/L] in the observation group were lower than those in the control group [(3.74±0.64)μg/L and (58.42±7.21)ng/L] ( t=13.864, 10.221, all P<0.05). The level of serum NO [(62.31±6.98)μmol/L] in the observation group was higher than that in the control group [(54.39±4.51)μmol/L], while ET-1 [(58.74±6.21)μg/L] was lower than that in the control group [(76.29±4.56)μg/L], and the differences were statistically significant between the two groups( t=7.382, 17.645, all P<0.05). Conclusion:Nicorandil is effective in the treatment of patients with coronary heart disease, and can reduce the levels of MMP-9 and VEGF in serum, and improve the function of vascular endothelium.

OBJECTIVE: To determine the incidence of surgical site infection (SSI) after abdominal surgery and to further evaluate the related risk factors of SSI in China. METHODS: The multicenter cross-sectional study collected clinical data of all adult patients who underwent abdominal surgery from May 1, 2018 to May 31, 2018 in 30 domestic hospitals, including basic information, perioperative parameters, and incisional microbial culture results. The primary outcome was the incidence of SSI within postoperative 30 days. SSI was classified into superficial incision infection, deep incision infection, and organ/gap infection according to the US Centers for Disease Control and Prevention (CDC) criteria. The secondary outcome variables were ICU stay, postoperative hospital stay, total hospital stay, 30-day mortality and treatment costs. Multivariate logistic regression was used to analyze the risk factors of SSI. RESULTS: A total of 1666 patients were enrolled in the study, including 263 cases of East War Zone Hospital of PLA, 140 cases of Affiliated Hospital of Qingdao University, 108 cases of The First Affiliated Hospital of Nanchang University, 87 cases of Central War Zone Hospital of PLA, 77 cases of West China Hospital, 74 cases of Guangdong General Hospital, 71 cases of Chenzhou First People's Hospital, 71 cases of Zigong First People's Hospital, 64 cases of Zhangjiagang First People's Hospital, 56 cases of Nanyang City Central Hospital, 56 cases of Lanzhou General Hospital of Lanzhou Military Command, 56 cases of Shandong Provincial Hospital, 52 cases of Shangqiu First People's Hospital, 52 cases of People's Hospital of Xinjiang Uygur Autonomous Region, 48 cases of The Second Xiangya Hospital of Central South University, 48 cases of Chinese PLA General Hospital, 44 cases of Affiliated Hospital of Xuzhou Medical University, 38 cases of Hunan Province People's Hospital, 36 cases of Dongguan Kanghua Hospital, 30 cases of Shaoxing Central Hospital, 30 cases of Northern Jiangsu People's Hospital, 29 vases of The First Affiliated Hospital of Zhengzhou University, 27 cases of General Hospital of Tianjin Medical University, 22 cases of Zigong Fourth People's Hospital, 21 cases of The Second Hospital of University of South China, 18 cases of Tongji Hospital, 15 cases of Nanchong Central Hospital, 12 cases of The 901th Hospital of PLA, 11 cases of Hunan Cancer Hospital, 10 cases of Lanzhou University Second Hospital. There were 1019 males and 647 females with mean age of (56.5±15.3) years old. SSI occurred in 80 patients (4.8%) after operation, including 39 cases of superficial incision infection, 16 cases of deep incision infection, and 25 cases of organ/interstitial infection. Escherichia coli was the main pathogen of SSI, and the positive rate was 32.5% (26/80). Compared with patients without SSI, those with SSI had significantly higher ICU occupancy rate [38.8%(31/80) vs. 13.9%(220/1586), P<0.001], postoperative hospital stay (median 17 days vs. 7 days, P<0.001) and total hospital stay (median 22 days vs. 13 days, P<0.001), and significantly higher cost of treatment (median 75 000 yuan vs. 44 000 yuan, P<0.001). Multivariate analysis showed that male rise(OR=2.110, 95%CI:1.175-3.791, P=0.012), preoperative blood glucose level rise(OR=1.100, 95%CI: 1.012-1.197, P=0.026), operative time (OR=1.006, 95%CI:1.003-1.009, P<0.001) and surgical incision grade (clean-contaminated incision:OR=10.207, 95%CI:1.369-76.120, P=0.023; contaminated incision: OR=10.617, 95%CI:1.298-86.865, P=0.028; infection incision: OR=20.173, 95%CI:1.768-230.121, P=0.016) were risk factors for SSI; and laparoscopic surgery (OR=0.348, 95%CI:0.192-0.631, P=0.001) and mechanical bowel preparation(OR=0.441,95%CI:0.221-0.879, P=0.020) were protective factors for SSI. CONCLUSIONS The incidence of postoperative SSI in patients with abdominal surgery in China is 4.8%. SSI can significantly increase the medical burden of patients. Preoperative control of blood glucose and mechanical bowel preparation are important measures to prevent SSI.
Abdomen ; surgery ; Adult ; Aged ; China ; Cross-Sectional Studies ; Female ; General Surgery ; statistics & numerical data ; Humans ; Male ; Middle Aged ; Operative Time ; Postoperative Complications ; prevention & control ; Preoperative Period ; Retrospective Studies ; Risk Factors ; Surgical Wound Infection ; prevention & control

Objective : To investigate the changes of vaspin and TNF-α levels in gingival crevicular fluid (GCF) of type 2 diabetic (T2DM) patients with chronic periodontitis (CP) after non-surgical periodontal treatment. Methods: 60 subjects were divided into 4 groups: DM-CP group (patients with both T2DM and CP, n=15); CP group (CP patients without T2DM, n=15); DM group (T2DM patients without CP, n=15), and CTRL group (systemically and periodontally healthy individuals, n=15). The clinical parameters of periodontal tissue and GCF were measured before and 8 weeks after non-surgical periodontal treatment. Results: The levels of vaspin and TNF-α were measured by ELISA. The levels of vaspin and TNF-α in CP group were significantly higher than those in CTRL group (P < 0.05), while the levels of vaspin and TNF-α in CP group were significantly decreased after treatment (P < 0.05). There was a statistically significant positive correlation between the total amount of vaspin and the total amount of TNF-α, the level of HbA1c, gingival index (GI) and probing depth (PD) (P < 0.05). Conclusion The results shows that vaspin and TNF-α are greatly decreased in periodontitis after non-surgical periodontal treatment. It suggests that vaspin and TNF-α in GCF may serve as inflammatory markers for the diagnosis and prognosis of diabetes and periodontitis.