Objective To investigate the clinical efficacy of hydrogen-rich water (HRW) combined with oxycodone hydrochloride controlled-release tablets (OHCT) in the treatment of malignant neuropathic pain (MNP) patients.Methods Eighty MNP patients were randomly divided into two groups:OHCT group (group A,n =40) and HRW combined OHCT group (group B,n =40).The visual analog scale (VAS) score,frequency of pain outbreaks,pain relief rate,average dose of OHCT per day,and adverse reactions were observed.Results The VAS scores and frequency of pain outbreaks in groups A and B were significantly reduced after treatment (P ＜0.05).Compared to group A,the VAS scores,pain relief rate,outbreak pain and average dose of OHCT per day in group B were significantly improved after 14 and 28 days of treatment (P ＜ 0.05),and the adverse reactions,such as constipation,nausea and vomiting,in group B were significantly less than those in group A (P ＜ 0.05).Conclusions HRW combined with OHCT can effectively improve the MNP,and reduce average dose of OHCT per day and adverse reactions.

Objective To systematically review the effectiveness and safety of transcutaneous electricalnerve stimulation (TENS) on symptomatic diabetic neuropathy (DNP). Methods Electronic databases such asPUBMED, EMBASE, Cochrane Central Register of Controlled Trials, and Chinese Biomedical Database weresearched by using such mesh and text keywords as "TENS" and "diabetic neuropathy". Randomized controlled trials(RCTs) on the effect of TENS on symptomatic diabetic neuropathy were included. Studies were selected and availa-ble data was extracted independently by two reviewers. Meta-analysis was performed using RevMan 4.2.8 software.Results Three RCTs involving 78 patients were included in this study. Compared with sham-stimulation, TENStherapy significantly reduced the score in pain (SMD -2.35, 95% CI [-4.24, -0.46 ] ) and the score in numb-ness (WMD -0.18, 95% CI [-0.32, -0.05 ] ). Subgroup analysis shows that TENS therapy was associated with a significant reduction in the score of pain in both 4-week treatment duration ( SMD - 5.37, 95% CI [ - 6.97,- 3.77 ] ) and 6-week treatment duration ( SMD - 1.01, 95% CI [ - 2.01, - 0.01 ] ), but not 12-week treatmentduration (SMD - 1.65, 95% CI [ -4.02, 0.73 ] ). Conclusion TENS therapy is a promising and safe strategyfor treatment of symptomatic diabetic neuropathy. More studies are still warranted to accumulate the evidence of theeffect of TENS therapy on DNP.

Objective To investigate the effects of telmisartan on the expression of angiotensin converting enzyme2 (ACE2) mRNA in monocyte-derived macrophages of hypertensive patients companied with diabetes.Methods 62 essential hypertensive patients companied with diabetes were randomly divided into two groups:regular treatment group,and telmisartan group.Then the content of ACE and ACE2 in serum was detected by ELISA,and the expression of ACE mRNA and ACE2 mRNA in monocyte-derived macrophages of patients was detected by RT-PCR before and after having been treated.Results (1) After having been treated for 4 weeks and 12 weeks,the blood pressure of the patients in two groups were decreased significantly,Comparing with regular group,telmisartan group seemed to have more obvious therapeutic effect (P ＜ 0.05) ; (2) After having been treated for 12 weeks,glycosylated hemoglobin diseased in both group,but there was no significant difference between the two group (P ＞ 0.05) ; (3) In telmisartan group,the content of ACE2 in serum was increased after having been treated for 12 weeks than that in regular treatment group,[(23.9 ± 8.2) U/L vs (16.3 ± 8.9) U/L,P ＜ 0.05] ; and the expression of ACE2 mRNA in monocyte-derived macrophages in telmisartan group was obviously increased after 12 weeks comparing with regular treatment group (0.73 ±0.06 vs 0.51 ±0.04,P ＜0.01).Conclusion The role of telmisartan in decreasing blood pressure and it's advantage to the metabolism of glucose are partly related with the up-regulation of ACE2 mRNA.

Objective To explore the protective mechanism of HSP70 protein in traumatic brain injury (TBI)‐related acute gastric mucosal lesions in mice .Methods Forty adult male Balb/c mice were randomly divided into sham (A) ,TBI (B) ,TBI+ geranylgeranylacetone (GGA) (C) ,and TBI+saline (D) groups .TBI was induced via the Feeney impact model .GGA (800 mg/kg) was administered via oral tube beginning before the model was built in group C .The expressions of HSP70 protein in brain and gastric mucosa were determined by immunohistochemistry , and the apoptotic index was detected by TUNEL method .Results The injury area in mouse brain and gastric mucosa was greater in group B than in groups A and C (P<0 .05) .After model induction ,the content of HSP70 protein in group B was markedly higher in the brain and gastric mucosa ,which was notably higher than in group A (P<0 .05) .Obviously apoptotic cells were observed in groups B and D ,which were significantly higher than in groups A and C .GGA pretreatment enhanced the up‐regulated expression of HSP70 and decreased the apoptotic index distinctly ;HSP70 expression was higher in group C than in groups B and D ,but the apoptotic index was lower (P<0 .05) .Conclusion GGA can induce HSP70 protein expression in mouse brain and gastric mucosa .HSP70 is involved in the process of apoptosis inhibition .GGA can be used in the prevention and therapy of TBI‐related acute gastic mucosal lesions .

Objective To evaluate the effect of hydrogen-rich saline on neuropathic pain in rats.Methods One hundred and twenty male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 4 groups (n =30 each) using a random number table:sham operation group (S group); hydrogen-rich saline group (H group); chronic constrictive injury (CCI) group; CCI + hydrogen-rich saline group (CH group).Neuropathic pain was induced by CCI.The animals were anesthetized with intraperitoneal 10％ chloral hydrate 300 mg/kg.The left sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals.In H and CH groups,hydrogen-rich saline 10 ml/kg was injected intraperitoneally twice a day for 3 consecutive days starting from 1 day after CCI.The paw withdrawal threshold to mechanical stimulation with yon Frey filament (PWT) and paw withdrawal latency to thermal stimulation (PWL) were measured on the day before CCI (T0) and on 3,5 and 7 days after CCI (T1-3).The rats were sacrificed after the last measurement of pain threshold at T4.The left lumbar segments (L4-6) of the spinal cord were removed for determination of the contents of tumor necrosis factor-alpha (TNF-α),interleukin-1β (IL-1β),interleukin-6(IL-6) and high-mobility group box-1 (HMGB1) (by ELISA),and malondialdehyde (MDA) content and superoxide dismutase (SOD) and catalase (CAT) activities (using visible spectrophotometer).Results Compared with S group,PWT was significantly decreased,PWL was shortened,the contents of TNF-α,IL-1β,IL-6,HMGB1 and MDA were increased,and the activities of SOD and CAT were decreased at each time point after CCI in CCI and CH groups.Compared with CCI group,PWT was significantly increased,PWL was prolonged,the contents of TNF-α,IL-1β,IL-6,HMGB1 and MDA were decreased,and the activities of SOD and CAT were increased at all the time points after CCI in group CH.Conclusion Hydrogen-rich saline can alleviate neuropathic pain in rats via reducing the inflammatory response and lipid peroxidation response.

Aim To investigate the effects of metformin on phospho-signal transducers and activators of transcription 3(p-STAT3) expression in the spinal dorsal horn in rats with bone cancer pain(BCP).Methods Healthy female SD rats weighing 200~220 g were randomly divided into four groups(n=12 each): Sham+NS, Sham+Metformin, BCP+NS, BCP+Metformin groups.Normal saline or metformin(200 mg·kg-1) was given intraperitoneally once a day at 7~14 day after surgery in four groups.Mechanical withdrawal threshold(MWT) was measured on-1, 3, 5, 7, 10, 12, 14 day after BCP.The L4-6 segments of spinal cords were used to detect the expression of p-STAT3 by Western blot and immunohistochemical staining technique after the behavioral test was completed on day 14.Results Intraperitoneal injection of metformin reversed hyperalgesia and suppressed the expression of p-STAT3 in BCP rats.Conclusion Metformin can attenuate BCP by inhibiting the expression of p-STAT3 in the spinal dorsal horn.

Objective To investigate the capability of 99 Tcm?tricine?EDDA/HYNIC?SFSIIHTPILPL ( SP94) as a specific probe for HCC imaging. Methods HYNIC?SP94 peptide was prepared by solid phase synthesis, followed by 99 Tcm labeling with tricine?EDDA as the coligand. After determination of radiochemical purity and stability, cell binding study was carried out by incubating Huh?7 cells with 99 Tcm?tricine?EDDA/HYNIC?SP94 at different specific activities (2.5, 4.0 and 30.0 GBq/μmol). The biodistribution studies and microSPECT/CT imaging were performed in Huh?7 tumor?bearing mice ( study group) and Hela tumor?bear?ing mice ( control group ) . Statistical analysis was by two?sample t test. Results 99 Tcm?tricine?EDDA/HYNIC?SP94 was synthesized with over 95% of labeling yield, which remained stable in saline and FBS up to 12 h. With increasing concentrations of 99 Tcm?tricine?EDDA/HYNIC?SP94, Huh?7 cell binding increased but became gradually saturated. In biodistribution studies, (1.02±0.26) %ID/g of tracer was accumulated in Huh?7 tumors at 0.5 h after injection of 99 Tcm?tricine?EDDA/HYNIC?SP94, higher than that in the HYNIC?SP94 blocking group ((0.34±0.09) %ID/g;t=3.537, P<0.05). Compared to Hela tumors, Huh?7 tumors were clearly visualized by microSPECT/CT, with which better imaging quality could be achieved with higher specific radioactivity. Conclusion 99 Tcm?tricine?EDDA/HYNIC?SP94 could achieve a high labeling effi?ciency and good in vitro stability as a potential diagnostic tracer specifically targeted for HCC.

Noise is a common occupational hazard in workplaces. Long-term exposure to high-intensity noise mainly causes occupational noise-induced hearing loss (ONIHL). The development of ONIHL is irreversible, and there is currently no cure. At present, risk assessment methods based on noise exposure intensities mainly include risk index assessment method, Engineering Professional Council assessment method in United Kingdom (EDC assessment method in UK), National Institute of Occupational Safety and Health assessment method in United State (NIOSH assessment method in US), and International Standardization Organization assessment method (ISO assessment method). However, the risk index assessment method is subjective and does not consider the effectiveness of workers wearing protective equipment. The EDC assessment method in UK defines ONIHL differently from China. The NIOSH assessment method in US and ISO assessment methods have population data sources that deviate from China, which can lead to bias in risk assessment. In the future, it is necessary to further carry out application research on the risk assessment of ONIHL in Chinese noise-exposed workers, compare the applicabilities of various assessment methods, conduct large-sample population epidemiological studies for verification, and fully utilize the risk-prediction function to prevent and control ONIHL.

Objective: To explore the effectiveness of preventive treatment for latent tuberculosis infection (LTBI) patients, so as to provide reference for the management and preventive treatment of clustered epidemic in schools. Methods: Data came from the school tuberculosis outbreak of a boarding high school in Kaizhou District, Chongqing, which occurred between June 2017 and March 2018 among 2016 grade high school teachers and students for investigation and analysis. The total incidence, LTBI patients, and the incidence after preventive treatment for 5 years were followed up. Results: A total of 34 cases of pulmonary tuberculosis from June 2017 to March 2018. A total of 1 357 individuals were screened for 6 concentrated contact screenings, with a confirmed tuberculosis rate of 2.43%, a tuberculosis skin test (TST) positive rate of 27.41%, and a strong TST positive rate of 7.39%. Among them, the confirmed tuberculosis rate and TST positive rate in the first case class were much higher than those in other classes, with statistically significant differences ( χ 2=286.30, 98.59, P ＜0.01). 88 cases of LTBI were found, with 31 cases receiving preventive treatment (35.23%), of which 28 completed preventive treatment (90.32%). After five years of follow-up, 73 cases of pulmonary tuberculosis were diagnosed in 2016 by the school senior high school, with a incidence rate of 0.98/10 2 (person/person years). Fifteen of the 88 LTBI patients were diagnosed with pulmonary tuberculosis, and the incidence rate was 3.33/10 2 (person/person years). The incidence rate of the preventive treatment group was 0.7/10 2 (person/person years)lower than that of the medical observation group 4.5/10 2 (person/person years), with a statistically significant difference ( χ 2=4.31, P ＜0.05). Conclusion The classes with higher TST positive rate and strong positive rate have higher incidence rate. Improving the preventive treatment rate of LTBI patients can effectively reduce the incidence rate of tuberculosis.

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.
Humans ; Rabies Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing ; Rabies virus ; Vaccination ; Rabies/prevention & control*