Visceral leishmaniasis is a zoonotic parasitic disease caused by viscerotropic Leishmania species and transmitted by bites of infected phlebotomine sandflies, which is predominantly prevalent in the Indian subcontinent, eastern Africa and South America. Currently, visceral leishmaniasis is the second most fatal parasitic disease in the world. Because of climate changes, urban development and individual conditions, there are changes in the density of visceral leishmaniasis vector sandflies and the likelihood of contact with humans, resulting in a visceral leishmaniasis transmission risk. The review summarizes natural, social and biological factors affecting the transmission of visceral leishmaniasis, so as to provide insights into formulation of targeted control measures for visceral leishmaniasis.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Objective:To explore the effect of enhanced recovery after surgery (ERAS) protocols in patients undergoing laparoscopic radical cystectomy (LRC) and intracorporeal urinary diversion (ICUD).Methods:A total of 83 patients who received LRC+ ICUD in Beijing Chaoyang Hospital from March 2014 to September 2020, were divided into 2 groups based on different perioperative management, including 29 ERAS cases and 54 conventional recovery after surgery (CRAS) cases. The ERAS group included 26 males and 3 females , with an average age of (62.07 ± 9.26) years. There were 26 patients with ASA class Ⅰ-Ⅱ, 3 patients with ASA class Ⅲ, 4 patients received neoadjuvant chemotherapy, and 7 patients had a history of abdominal surgery in ERAS group. The CRAS group included 44 males and 10 females , with an average age of (61.59 ± 10.16) years. There were 50 patients with ASA class Ⅰ-Ⅱ, 4 patients with ASA class Ⅲ, 9 patients received neoadjuvant chemotherapy, and 10 patients had a history of abdominal surgery in CRAS group. There were no statistically significant differences in the baseline characteristics between the two groups. The patients in both groups underwent LRC+ ICUD procedures. The perioperative results and complications between the two groups were compared.Results:In the ERAS group, there were 20 patients who underwent Bricker ileal conduit surgery and 9 patients who underwent Studer orthotopic ileal neobladder surgery. Pathological staging included 3, 3, 7, 7, 5 and 4 cases in stage T a, T is, T 1, T 2, T 3 and T 4a, respectively. There were 23, 2, 3 and 1 patient with pathological stage N 0, N 1, N 2 and N 3, respectively. Pathological diagnosis included 3 cases of low-grade urothelial carcinoma, 24 cases of high-grade urothelial carcinoma, and 2 cases of other histological subtypes. In the CRAS group, there were 31 patients who underwent Bricker ileal conduit surgery and 23 patients who underwent Studer orthotopic ileal neobladder surgery. Pathological staging included 5, 3, 12, 9, 15 and 10 patients in stage T a, T is, T 1, T 2, T 3 and T 4a, respectively. There were 35, 6, 7 and 6 patients with pathological stage N 0, N 1, N 2, and N 3, respectively. Pathological diagnoses included 6 cases of low-grade urothelial carcinoma, 45 cases of high-grade urothelial carcinoma, and 3 cases of other histological subtypes. There were no statistically significant differences ( P>0.05) in surgical methods, pathological staging, or pathological types between the ERAS and CRAS groups. ERAS group presented less albumin loss [(25.73±8.63)% vs. (32.63±9.05)%, P=0.001], shorter hospital stay [9(7, 13)d vs. 12(9, 16)d, P=0.006], less 30-day overall complications [55.2% (16/29) vs. 83.3% (45/54), P=0.009]. In multivariable analysis, maximum albumin loss≥20% was independently associated with 30-day minor complications ( P=0.049), and maximum albumin loss ≥25% was independently associated with hospital of stay≥10 days ( P=0.038), respectively. Conclusions:For patients who received LRC+ ICUD, ERAS was associated with reduced perioperative albumin loss, shorter length of stay, less 30-day complications, accelerated recovery time, improved clinical outcome and less albumin injection.

Cadmium (Cd) is a common heavy metal in the environment. Cd²⁺ may penetrate the blood-brain barrier and produce neurotoxicity, thus inducing various neurodegenerative diseases. Celastrol is an effective component of Tripterygium wilfordii Hook. F., which has many pharmacological effects such as anti-cancer and anti-inflammatory. Here we explored the effect of celastrol on the corresponding neurotoxicity induced by Cd²⁺. Cell proliferation test, cell membrane integrity test, and cell morphology were observed to analyze the effect of Cd²⁺ on the viability of HMC3. The neurotoxicity of Cd²⁺ and the effect of celastrol on the corresponding neurotoxicity induced by Cd²⁺ were analyzed by nitric oxide (NO) test, lipid peroxidation (MDA) test, and Western blotting. When the concentration of Cd²⁺ reached 40 μmol/L, the inhibition rate of HMC3 cell proliferation was (57.17±8.23)% (P < 0.01, n=5), compared with the control group. The cell activity continued to reduce when the Cd²⁺ concentration further increased. When the concentration of Cd²⁺ was higher than 40 μmol/L, the cell membrane of HMC3 was significantly damaged, and the damage was dose-dependent. Upon increasing the Cd²⁺ concentration, the cell morphology began to change and the adhesion also became worse. Cd²⁺ significantly increased the amount of NO released by HMC3 cells, while celastrol effectively inhibited the NO release of HMC3 cells induced by Cd²⁺. Cd²⁺ greatly increased the release of MDA in HMC3 cells, and the level of MDA decreased rapidly upon the addition of 10^-7 mol/L celastrol. Cd²⁺ increased the expression of p-PI3K protein, and the levels of p-PI3K protein and p-AKT protein were inhibited by the addition of celastrol (10^‒7 mol/L, 10^‒6 mol/L), thus preventing cell apoptosis. In conclusion, celastrol inhibits Cd²⁺ induced microglial cytotoxicity and plays a neuroprotective role.
Anti-Inflammatory Agents/pharmacology* ; Apoptosis ; Cadmium/toxicity* ; Nitric Oxide/pharmacology* ; Pentacyclic Triterpenes ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt/metabolism* ; Triterpenes/pharmacology*

Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain-Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.
Adult ; Animals ; Drug Repositioning ; Humans ; Infant, Newborn ; Microcephaly ; Pharmaceutical Preparations ; Zika Virus ; Zika Virus Infection/prevention & control*

Objective:To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China.Methods:Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women′s socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis.Results:A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95% CI: 4.5%－6.1%) and 13.1% (95% CI: 11.3%－14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions:In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.

The medical imaging technology (MIT) specialty hasn't been set up for a long time in China, and the mode of educating students in other institutions vary greatly among different universities. There are several disadvantages in MIT specialty set up in the Affiliated hospitals of universities, such as unreasonable curriculum system, imperfections in teaching and research department, and inadequate guidance on students' innovation ability. Therefore, the solutions for alleviating the above problems that are unfavorable factors to education are proposed, so as to further improve the model of MIT specialty set up in the affiliated hospitals of universities and produce more competent graduates.

Objective     To explore the effect of standardized use of antibiotics on clinical indicators after thoracic surgery, such as pulmonary infection rate, incision infection rate, average length of hospital stay and total hospitalization cost. Methods     We selected 468 patients (an observation group) who were hospitalized and received thoracic surgery from August to October 2011, 3 months after the implementation of the preventive antibiotics use protocol for thoracic surgery in West China Hospital, Sichuan University, and selected 343 patients (a control group) in the same period of the previous year (from August to October 2010). There were 326 males and 142 females with a mean age of 52.0±15.5 years in the observation group, and 251 males and 92 females with a mean age of 51.4±15.9 years in the control group. The level of antibiotic use, medication time, antibiotics cost, postoperative incision infection, incidence of pulmonary infection, postoperative hospital stay and total hospitalization cost were compared between the two groups. Results     Compared with the control group, the time for preventive use of antibiotics was significantly shorter in the observation group (3.6±2.4 d vs. 6.1±3.1 d, P=0.020) and the total cost of antibiotic use significantly reduced (1 230.0±2 151.0 yuan vs. 2 252.0±1 764.0 yuan, P<0.001). There was no significant difference between the two groups in hospitalization cost (36 345.0±13 320.0 yuan vs. 35 821.0±11 991.0 yuan, P=0.566), postoperative hospital stay (10.6±8.4 d vs. 10.7±5.3 d, P=0.390), the incidence of postoperative wound infection or postoperative pulmonary infection (1.5% vs. 2.3%, P=0.430; 19.2% vs. 22.2%, P=0.330). Conclusion     The standardized use of antibiotics in thoracic surgery does not cause   postoperative pulmonary infection and incision infection, and has no negative impact on clinical indicators. Significantly reducing the level of antibiotics use may have a positive effect on reducing medication time, in-hospital infection and the incidence of drug-resistant strains.

Objective To explore the perioperative outcomes and safety of enhanced recovery after surgery (ERAS) in laparoscopic radical cystectomy (LRC).Methods We retrospectively evaluated outcome of 10 LRC patients on ERAS protocol from May 2017 to October 2017,and 39 LRC patients on conventional recovery after surgery(CRAS) protocol from July 2015 to November 2016.There were (60.9 ±11.4) years and (63.7 ± 12.1) years in ERAS group and CRAS group respectively(P =0.514);(25.5 ±2.7) kg/m2 and (24.4 ± 3.6) kg/m2 with body mass index (P =0.375).Both of the median of charlson comorbidity index (P =0.931) and American Society of Anesthesiologists score (P =0.254) were 2 There was no statistical significance between the two groups for type of urinary diversion and preoperative laboratory studies (P ＞ 0.05).Patients' perioperative outcomes,early (30-day) complications and postoperative readmission rate were compared.Results The ERAS group had less intraoperative crystalloid infusion [(950.0 ± 474.3) ml vs.(1 797.4 ± 448.1) ml,P ＜ 0.001],faster removed gastric tube (0 d vs.4 d,P ＜0.001),and shorter passing flatus time [(1.6 ± 0.8) d vs.(2.9 ± 1.4) d,P =0.006] than the CRAS group;however,no difference was found in terms of intraoperative colliod infusion [(1 110.0 ± 331.5)ml vs.(1 117.9 ± 397.9) ml,P =0.954].No patients from either group required conversion to open surgery.There was no significant difference between the two groups for operative time (P =0.311),estimated blood loss (P =0.073),drain days (P =0.681),postoperative hospital stay (P =0.509),overall blood transfusion (P =1.000),intensive care unit stay (P =1.000) and tumor characteristics (pathological stage,histology,nodes removed,positive nodes,lymph node-positive patients,positive surgical margins).The 30-day postoperative complications were documented in 5 (50％)and 23 (59％)patients in groups ERAS and CRAS (P =0.878),respectively.And the most common complication were minor complications (Clavien-Dindo grade 1 and 2) in both groups (100.0％ vs.86.9％,P =0.729).The 30-day readmission rate was 20.0％ (2 patients) in ERAS group and 10.3％ (4 patients) in CRAS group with no statistical significance(P =0.588).Conclusions Our ERAS protocol expedited bowel function recovery after RC and urinary diversion without increasing in 30-day complications compared with CRAS.The key of implement ERAS pathway is to explore and develop their own protocol conformed to their medical treatment enviroment.