An Artificial Enzyme for Asymmetric Nitrocyclopropanation of α,ß-Unsaturated Aldehydes-Design and Evolution.

The introduction of an abiological catalytic group into the binding pocket of a protein host allows for the expansion of enzyme chemistries. Here, we report the generation of an artificial enzyme by genetic encoding of a non-canonical amino acid that contains a secondary amine side chain. The non-canonical amino acid and the binding pocket function synergistically to catalyze the asymmetric nitrocyclopropanation of α,ß-unsaturated aldehydes by the iminium activation mechanism. The designer enzyme was evolved to an optimal variant that catalyzes the reaction at high conversions with high diastereo- and enantioselectivity. This work demonstrates the application of genetic code expansion in enzyme design and expands the scope of enzyme-catalyzed abiological reactions.

Chemoenzymatic synthesis of (+)-isoagatholactone, (+)-spongian-16-one, and 3-deoxychavalone A via biocatalytic polyene cyclization.

The stereoselective cyclization of geranylgeraniol catalysed by squalene-hopene cyclase (SHC) was investigated. By use of this transformation, spongiane diterpenoids (+)-isoagatholactone and (+)-spongian-16-one, and meroterpenoid 3-deoxychavalone A were synthesized in a concise and redox-economic manner. This work showcases the application of SHC-catalysed cyclization as a key step in terpenoid synthesis.

Enantioselective conjugate addition of malonates to α,ß-unsaturated aldehydes catalysed by 4-oxalocrotonate tautomerase.

The enantioselective conjugate addition of malonates to α,ß-unsaturated aldehydes catalysed by 4-oxalocrotonate tautomerase is described. High conversions, high enantioselectivities, and good isolation yields were achieved for a range of substrates. We further completed a four-step synthesis of the antidepressant (+)-femoxetine by utilizing this reaction and an enzymatic reductive amination reaction.

[Berberine hydrochloride inhibits benign prostatic hyperplasia in rats by activating the Nrf2/ARE pathway].

Objective: To study the inhibitory effect of berberine hydrochloride (BBR) on BPH and its underlying mechanism in male rats. METHODS: Forty male rats were randomly divided into a normal control, a BPH model control, a BBR intervention, and a BBR+Bruceol intervention group, and the BPH model was established in the latter three groups. The animals in the normal and BPH model control groups were treated intragastrically with normal saline, and those in the BBR and BBR+Bruceol intervention groups with BBR at 200 mg/kg and BBR plus Bruceol at 1 mg/kg, respectively, once a day for 14 consecutive days. The prostates of the rats were harvested for measurement of their wet weight and prostatic index, detection of the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) and determination of the protein expressions of nuclear factor E2-related factor 2 (Nrf2), antioxidant response element (ARE) and reduced coenzyme I quinone oxidoreductase (NQO1) in the prostate tissue by Western blot. RESULTS: The wet weights of the prostate in the normal control, BPH model control, BBR intervention, and BBR+Bruceol intervention groups were (715.63 ± 28.57) mg, (1118.93 ± 36.41) mg, (896.21 ± 20.24) mg and (967.23 ± 24.98) mg, the prostate indexes were 2.10 ± 0.13, 3.45 ± 0.22, 2.75 ± 0.19 and 3.01 ± 0.14, the SOD contents in the prostate tissue were (38.54 ± 5.12) U/mg, (13.98 ± 2.01) U/mg, (26.75 ± 3.19) U/mg and (20.16 ± 4.10) U/mg, and the MDA contents were (3.59 ± 0.83) nmol/mg, (12.63 ± 3.26) nmol/mg, (7.20 ± 1.69) nmol/mg and (9.85 ± 1.71) nmol/mg, respectively. The relative expressions of the Nrf2 protein in the four groups were 0.53 ± 0.06, 0.12 ± 0.03, 0.36 ± 0.04 and 0.25 ± 0.03, those of the ARE protein were 0.69 ± 0.07, 0.21 ± 0.02, 0.50 ± 0.06 and 0.30 ± 0.04, and those of the NQO1 protein were 0.44 ± 0.05, 0.15 ± 0.03, 0.30 ± 0.04 and 0.22 ± 0.03, respectively. There were statistically significant differences in all the above indicators between the normal and BPH model control groups (P < 0.05), as well as between the BPH model control and BBR intervention groups (P < 0.05) and between the BPH model control and the BBR+Bruceol intervention groups (P < 0.05). CONCLUSIONS: BBR hydrochloride can inhibit prostatic hyperplasia in BPH rats and reduce oxidative stress and pathological changes by activating the Nrf2/ARE pathway.

Helichrysetin inhibits gastric cancer growth by targeting c-Myc/PDHK1 axis-mediated energy metabolism reprogramming.

Helichrysetin (HEL), a chalcone isolated from Alpinia katsumadai Hayata, has an antitumor activity in human lung and cervical cancers. However, the inhibitory effect and underlying mechanism of HEL in gastric cancer have not been elucidated. Here, HEL significantly inhibited the growth of gastric cancer MGC803 cells in vitro and in vivo. HEL decreased expression and transcriptional regulatory activity of c-Myc and mRNA expression of c-Myc target genes. HEL enhanced mitochondrial oxidative phosphorylation (OXPHOS) and reduced glycolysis as evidenced by increased mitochondrial adenosine triphosphate (ATP) production and excessive reactive oxygen species (ROS) accumulation, and decreased the pPDHA1/PDHA1 ratio and Glyco-ATP production. Pyruvate enhanced OXPHOS after HEL treatment. c-Myc overexpression abolished HEL-induced inhibition of cell viability, glycolysis, and protein expression of PDHK1 and LDHA. PDHK1 overexpression also counteracted inhibitory effect of HEL on cell viability. Conversely, c-Myc siRNA decreased cell viability, glycolysis, and PDHK1 expression. NAC rescued the decrease in viability of HEL-treated cells. Additionally, HEL inhibited the overactivated mTOR/p70S6K pathway in vitro and in vivo. HEL-induced cell viability inhibition was counteracted by an mTOR agonist. mTOR inhibitor also decreased cell viability. Similar results were obtained in SGC7901 cells. HEL repressed lactate production and efflux in MGC803 cells. These results revealed that HEL inhibits gastric cancer growth by targeting mTOR/p70S6K/c-Myc/PDHK1-mediated energy metabolism reprogramming in cancer cells. Therefore, HEL may be a potential agent for gastric cancer treatment by modulating cancer energy metabolism reprogramming.

Uniportal thoracoscopic decortication for stage Ⅲ tuberculous empyema of 158 cases / 中华外科杂志

Objective: To examine the safety and feasibility of uniportal video-assisted thoracoscopic (VATS) decortication in patients presenting with stage Ⅲ tuberculous empyema. Methods: From August 2017 to July 2020, 158 patients of stage Ⅲ tuberculous empyema underwent uniportal VATS decortication with partial rib resection and customized periosteal stripper in Department of Thoracic Surgery, Shanghai Pulmonary Hospital. There were 127 males and 31 females, aged (M(IQR)) 32(28) years (range:14 to 78 years). Follow-up was performed in the outpatient clinic or via social communication applications, at monthly thereafter. If there was no air leak and chest tube drainage was less than 50 ml/day, a chest CT was performed. If the lung was fully re-expanded, chest tubes were removed. All patients received a follow-up chest CT 3 to 6 months following their initial operations which was compared to their preoperative imaging. Results: There was one conversion to open thoracotomy. The operative time was 2.75 (2.50) hours (range: 1.5 to 7.0 hours), and median blood loss was 100 (500) ml (range: 50 to 2 000 ml). There were no perioperative mortalities. There were no major complications except 1 case of redo-VATS for hemostasis due to excessive drainage and 1 case of incision infection, The incidence of prolonged air leaks (>5 days) was 80.3%(126/157). The postoperative hospital stay was 5.00 (2.25) days (range: 2 to 15 days). All patients were discharged with 2 chest tubes, and the median duration drainage was 21.00 (22.50) days (range: 3 to 77 days). Follow-up was completed in all patients over a duration of 20 (14) months (range: 12 to 44 months). At follow-up, 149 patients(94.9%) recovered to grade Ⅰ level, 7 patients to grade Ⅱ level, and 1 patient to grade Ⅲ level. Conclusion: Uniportal VATS decortication involving partial rib resection and a customized periosteal stripper is safe and effective for patients with stage Ⅲ tuberculous empyema.

[Galangin enhances autophagy by inhibiting NF-κB pathway in gastric cancer MGC-803 cells].

This study aimed to explore the effects of galangin on energy metabolism and autophagy in gastric cancer MGC803 cells and the underlying mechanism. Cell counting kit-8(CCK-8) was used to detect the effects of galangin at different concentrations on via-bility of MGC803 cells after 48 h intervention. Western blot was carried out to measure the effects of galangin on expression of proteins related to autophagy, nuclear factor-κB(NF-κB) pathway and energy metabolism, followed by the determination of its effects on mRNA expression of energy metabolism-related proteins by Real-time quantitative PCR(qPCR). The impact of galangin on autophagy was explored using AutophagyGreen dye reagent, with autophagosomes and lysosomes observed under the transmission electron microscope(TEM). Nude mice transplanted with gastric cancer MGC803 cells via subcutaneous injection were randomly divided into the following three groups: control(0.5% sodium carboxymethyl cellulose, once a day), 5-fluorouracil(5-FU, 50 mg·kg~(-1), twice a week), and galangin(120 mg·kg~(-1), once a day) groups. The body weight and tumor volume were measured once every three days with a vernier caliper at the same time point by the same person. After 21-d treatment, the tumor tissue was isolated and weighed for the calculation of the tumor-suppressing rate. The comparison with the control group revealed that galangin inhibited the viability of MGC803 cells, up-regulated the protein expression of microtuble-associated protein 1 light chain 3 B(LC3 B) Ⅱ, inhibited the phosphorylation of NF-κB pathway-related proteins, and promoted the formation of autophagosomes in MGC803 cells. However, it did not obviously affect the expression of energy metabolism-related proteins. Furthermore, galangin at 120 mg·kg~(-1) significantly reduced the tumor weight and volume in mice, enhanced LC3 BⅡ protein expression, and inhibited the phosphorylation of NF-κB pathway-related proteins. All these have suggested that galangin inhibited the growth of gastric cancer MGC803 cells both in vivo and in vitro, possibly by inhibiting the NF-κB pathway and enhancing autophagy.

Effectiveness and safety of warfarin and anti-platelet drugs for the primary prevention of stroke in patients with non-valvular atrial fibrillation: a meta-analysis.

OBJECTIVE: To evaluate the effectiveness and safety of warfarin and anti-platelet drugs as the primary approach to the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). METHODS: Three English databases (the Cochrane library, Embase, and Medline), and three Chinese databases (the Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, and Chinese Periodical Full-text Database of Science and Technology) were searched to select potentially eligible studies published before May, 2014. The studies were randomized controlled trials (RCTs) that investigated the effectiveness and safety of using warfarin and anti-platelet drugs in preventing stroke in NVAF patients; The statistical analysis was performed using the Review Manager 5.2 software provided by the Cochrane Collaboration. RESULTS: nine articles were finally included. Compared with antiplatelet drugs, warfarin treatment significantly reduced the risk of stroke (OR = 0.62, 95% CI 0.50-05.77), systemic embolism events (OR = 0.49, 95% CI 0.31-0.77), ischemic stroke events (OR = 0.46, 95% CI 0.36-0.59), stroke-related disability or death events (OR = 0.66, 95% CI 0.52-0.84). Warfarin did not increase the incidence of All-cause death events (OR = 0.92, 95% CI 0.78-1.08), intracranial hemorrhage events (OR = 1.28, 95% CI 0.85-1.93), major hemorrhage events (OR = 1.01, 95% CI 0.79-1.29). CONCLUSIONS: This meta-analysis found that compared with antiplatelet drugs, warfarin treatment significantly reduced the risk of stroke, systemic embolism events, ischemic stroke events, stroke-related disability or death events. And warfarin did not increase the incidence of All-cause death events, intracranial hemorrhage events, major hemorrhage events.

Protecting action of acupuncture-drug compound anesthesia with different frequency electroacupuncture on stress reaction in pneumonectomy / 中国针灸

<p><b>OBJECTIVE</b>To observe the protective effect of acupuncture-drug compound anesthesia with different frequency electroacupuncture on stress reaction in pneumonectomy and to explore potential mechanisms.</p><p><b>METHODS</b>Eighty patients scheduled for pneumonectomy were randomly divided into four groups, named group A, B, C and D, 20 cases in each group. General anesthesia and single lung protective mechanical ventilation were produced in all the groups. They were treated with acupuncture at Houxi (SI 3), Zhigou (TE 6), Neiguan (PC 6), and Hegu (Li 4) 30 min before general anesthesia, and then with Han's acupoint nerve stimulator (HANS-200). The acupuncture needles without needle bodies were pasted on the acupoints and the electroacupuncture were not turned on in group A, and the 2 Hz continuous wave were produced in group B, and 100 Hz continuous wave were produced in group C and the 2 Hz/100 Hz were produced in group D. The supplementary anesthesia medicine during pneumonectomy, heart rate (HR), mean arterial pressure (MAP), CD4+ /CD/ in venous blood before and after the surgery, and the contents of epinephrine (E) and cortisol (Cor) in plasma at the time of inter-room and outer-room were detected.</p><p><b>RESULTS</b>(1) The supplementary fentanyl in group B and C were lower than those in group A and D (P < 0.05, P < 0.01). (2) The MAP in the four groups at intratracheal intubation (T1) were all higher than those at before anesthesia (T0) (all P < 0.01), and the ascending extent in group B, C and D were lower than that in group A (all P < 0.01). The HR at T in group A was higher than that at T0 (P < 0.05) and there were no significant differences in the other groups (all P > 0.05), and the ascending extent in group B and D were lower than that in group A (both P < 0.05). The MAP and HR at the other moment in all the groups were maintained stable. (3) CD4+ /CD8+ in group A after pneumonectomy was lower than that before the surgery (P < 0.05), and there were no significant differences in the other groups (all P > 0.05). (4) The content of E and Cor after the surgery were all increased (all P < 0.01), and the ascending extent of E in group D was lower than that in group A (P < 0.05), and the ascending level of Cor in group B and D were lower than that in group A (P < 0.01) and group B compared with group C and D were got the same result.</p><p><b>CONCLUSION</b>Acupuncture-drug compound anesthesia can attenuate the stress reaction so as to protect organs under the condition of less drug and can alleviates the undulate phenomenon of MAP and HR at intubation and stabilize CD4+ /CD8+ after pneumonectomy. Among them, the 2 Hz and 2 Hz/100 Hz electroacupuncture groups have the comparatively better effects.</p>

Lung transplantation in a Chinese single center: 7 years of experience / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lung transplantation (LT) is a viable option for patients with end-stage lung diseases, but in China, the supply is limited, and the experience with LT is rare too. This study aimed to evaluate the survival and postoperative complications of recipients undergone LT.</p><p><b>METHODS</b>From January 2003 to May 2010, all patients who underwent LT were included. The clinical data of recipients were analyzed retrospectively, including demographic characteristics, survival rate, and the occurrences of postoperative complications, acute rejection and bronchiolitis obliterans syndrome.</p><p><b>RESULTS</b>In total, 37 patients underwent LT. The early mortality (≤ 30 days) was 14% (5/37). Cumulative survival rate was 78%, 70%, 70% and 42% at 1, 3, 5 and 6 years, respectively. In 37 patients, 5 (14%) developed fungal infections, 9 (24%) pulmonary bacterial infections, and 6 (16%) had bronchial anastomosis complications after LT. At three months post-transplantation, a significant improvement was observed in lung function (P < 0.05). Fifteen recipients (41%) developed acute rejection within the first year. Freedom from bronchiolitis obliterans syndrome was 89%, 85% and 80% at 1, 2 and 3 years after transplantation.</p><p><b>CONCLUSIONS</b>Despite the limited number of cases, the survival and occurrences of complications after LT were comparable to the international experience. Single LT may be a reasonable option for some patients with end-stage pulmonary diseases.</p>

Nineteen clinical features of fever in Chinese medicine.

Based on the 4,067 descriptions about fever in the medical records of the well-known Chinese medicine physicians throughout the ages, 19 different clinical features of fever are summarized as follows: chilly fever, high fever, low fever, dull fever, bones fever, alternating chills and fever, tidal fever, head fever, face fever, chest fever, back fever, abdomen fever, waist fever, palms and soles fever, lower extremity fever, afternoon fever, evening fever, postpartum fever, and menstrual fever. Although, some of these fever features have not be paid close attention to in Western medicine, stage-division and classification about fever in Western medicine deserve to be used by Chinese medicine for reference.

Cytokine responses after lobectomy for early non-small cell lung cancer: a prospective randomized comparison of video-assisted thoracic surgery and open thoracotomy / 中华外科杂志

<p><b>OBJECTIVE</b>To compare video-assisted thoracic surgery (VATS) and open thoracotomy (OT) on acute inflammatory responses and immunosuppression after lobectomy for early non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Present prospective randomized study. OT or VATS lobectomy was performed in patients who met enter criteria and clinical data was collected. Plasma concentration of IL-6, IL-8 and IL-10 were measured before surgery and at postoperative day (POD) 1 and POD 3. There were 271 patients underwent lobectomy for early NSCLC, including of 133 patients in group VATS and 138 patients in group OT from January 2007 to June 2008. There were 132 males and 139 females, aging from 19 ∼ 70 years with a mean of (56 ± 8) years.</p><p><b>RESULTS</b>Compared with OT group, shorter postoperative hospital stay [(8.2 ± 2.5) d vs. (9.8 ± 6.2) d, P = 0.03], lower morbidity rate (11.3% vs. 21.7%, P = 0.02) and lower increase of plasma concentration of IL-6 at POD 1 [(35 ± 25)% vs. (65 ± 43)%, P = 0.00], IL-6 at POD 3 [(14 ± 22)% vs. (55 ± 44)%, P = 0.00] and IL-10 at POD 1 [(25 ± 20)% vs. (43 ± 35)%, P = 0.00] were observed in patients of VATS group.</p><p><b>CONCLUSION</b>VATS lobectomy for early NSCLC is associated with less acute inflammatory responses and less immunosuppression when compared with OT.</p>

The early outcome of video-assisted thoracic surgery lobectomy for primary lung carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the early outcome of patients who underwent video-assisted thoracic surgery (VATS) lobectomy for primary lung carcinoma.</p><p><b>METHODS</b>The records of 121 patients with lung cancer undergoing VATS lung resection from 1997 to 2004 were reviewed retrospectively, I stage: 101 cases, 34 cases underwent right upper lobectomy, 13 cases underwent right middle lobectomy, 17 cases underwent right down lobectomy, 21 cases underwent left upper lobectomy, 16 cases underwent left down lobectomy. Thirty-eight cases underwent VATS lobectomy without assisted mini-incision.</p><p><b>RESULTS</b>There were 18 cases of morbidities (15%) and no surgical mortality. The 1-year, 2-year and 3-year survival rates of primary non-small cell lung cancer with I stage is: 99% (76/77), 96% (49/51) and 79% (15/19), respectively. There are statistic difference (P < 0.01) between adenocarcinoma and the others. There are no statistic difference (P > 0.05) between the VATS lobectomy with assisted mini-incision (n = 38) and without (n = 63), also no statistic difference (P > 0.05) between the VATS lobectomy and the standard procedure.</p><p><b>CONCLUSION</b>Our findings suggest that VATS lobectomy is superior regarding its ability to achieve the same survival rates and little morbidities in comparison with the standard procedure.</p>

[Reform steps of reestablishing disease prevention and control system of China].

OBJECTIVE: To develop and demonstrate the reform steps of reestablishing disease prevention and control system of China. METHODS: A model named "strategies of fulfilling public functions of disease prevention and control system of China" has been employed to develop reform steps. 154 centers for disease prevention and control (CDC) have been sampled to consult the opinions about the reform steps developed by research team. RESULTS: To reestablish the disease prevention and control system of China, the following reform steps should be kept to: (1) increase government's attention to disease prevention and control, (2) insure feasible government investment to disease prevention and control, (3) increase the stability and efficiency of government financing, (4) reform management system to enhance the operation efficiency of the CDC, (5) revise labor regulation to attract and stabilize specialists, (6) be carefully to dispose the non-public-service now delivered by the CDC. The consent percent of all sampling CDC was 98.7%.

[A study on the cause of public health service delivery insufficiency of disease prevention and control system of China].

OBJECTIVE: To demonstrate the cause of public health service delivery insufficiency of disease prevention and control system of China. METHODS: 205 literatures in 8 national academic journals concerning health service management have been reviewed. The method of boundary analysis has been employed to conclude the various causes of public health service delivery insufficiency of disease prevention and control system of China. RESULTS: Literatures review demonstrated that the financing from government to disease prevention and control system of China was insufficiency and show lower efficiency, which has been agreed by 99.3% of CDC. Literatures review demonstrated that the financing administration idea of permitting charging service caused the fee-for-service played a key role in the economic reimbursement of various levels of CDC, which has been agreed by 96.0% of CDC. CONCLUSION: The causes of public health service delivery insufficiency of disease prevention and control system of China were the government financing insufficiency and the defective administration strategies.

[Fundamental strategies to address the problem of public health service delivery insufficiency of disease prevention and control system of China].

OBJECTIVE: To develop and demonstrate the strategies to solve the problem of public health service delivery insufficiency of disease prevention and control system of China. METHODS: 205 literatures in 8 national academic journals concerning health service management have been reviewed. The method of boundary analysis has been employed to conclude the various reform strategies. Based on the causes and mechanism of public health service delivery insufficiency of disease prevention and control system, the logic analysis has been employed to develop fundamental strategies, which has been demonstrated by 154 CDC using intention questionnaires. RESULTS: There are fundamental strategies to which the agreeing rate for sampling CDC was over 95%: to make sure government should afford the financing function of disease prevention and control and secure the feasible investment for centers of disease prevention and control. Meanwhile, the working efficiency of CDC should be improved through strengthening management and reforming government investing manner.

[Results summarize of the project of "reestablishing disease prevention and control system of China"].

This paper introduced the following study results of the project of "reestablishing the disease control and prevention system of China" in brief: (1) the chief problem existed in disease control and prevention system of China is the lower fulfilling level of public functions. (2) the parents of this chief problem are the lower financing level and the lower managing responsibility of government. (3) to reestablish the disease control and prevention system of China, government should increase the investment and strengthen management, which may need the following preconditions: more government recognitions to the disease control and prevention, more government investment, more sustainable government investment, higher efficiency of CDC, more competitive salary system to recruit specialists, more reliable disposal about non-public-product provided by CDC. (4) the public functions of CDC could be defined as 7 categories and 255 items. (5) according to the calculating method of human resources allocation of CDC which has been developed and demonstrated by the project team, 159086 persons, which is equal to 76.9% of human resources of CDC in 2002, are needed to fulfill all the public function of CDC throughout the country. (6) based on the model of input-output analysis, to exclude the non-public-service of CDC, government should give another yen 10.29 billions on the basis of current 3.9 billions of government investment to CDC.

[The problem of public health service delivery insufficiency of disease prevention and control system of China].

OBJECTIVE: To demonstrate the chief problem existed in the disease control and prevention system of China. METHODS: Literatures in 8 national academic journals concerning health service management have been reviewed. The method of boundary analysis has been employed to conclude the various problems existed in the disease prevention and control system of China. RESULTS: 205 literatures have been carefully reviewed and 12 kinds of problems have been concluded. Furthermore, 98.0% investigated CDC agreed that the insufficiency of public health service delivery was the chief problem existed in the disease prevention and control system of China. CONCLUSION: Some powerful policies should be developed to increase the public health service delivery of the disease prevention and control system of China.