Improvement effects of glycyrrhizin on Helicobacter pylori-associated gastritis in rats and its mechanism / 中国药房

OBJECTIVE To investigate the improvement effects of glycyrrhizin （GL） on Helicobacter pylori （HP）-associated gastritis in rats and its mechanism. METHODS HP-associated gastritis rat model was induced by inoculating with 1×109 cfu/mL HP. The model rats were randomly divided into model group， positive control group （HP standard quadruple group）， GL low-dose， medium-dose and high-dose groups （5， 20， 50 mg/kg）， with 12 rats in each group. Another 12 healthy rats were selected as normal control group. Except the normal control group and model group were given constant volume of normal saline intragastrically， the other groups were given corresponding drugs intragastrically， once a day， for 30 consecutive days. After administration， rats received 13C urea breath test， and delta-over-baseline （DOB） was recorded； the pathological and cellular morphological changes of gastric mucosa in rats were observed， and pathological scoring was performed； the levels of interleukin-8 （IL-8）， IL-1β， tumor necrosis factor-α （TNF-α）， reactive oxygen species （ROS） and malondialdehyde （MDA） were detected in gastric mucosa of rats； mRNA expressions of high mobility group box-1 protein （HMGB1） and nuclear factor-κ-B （NF-κB）， relative expressions of nitric oxide synthases （iNOS） and HMGB1， the phosphorylation level of NF- κBp65 were also detected in rats. RESULTS Compared with normal control group， the DOB value， histopathological score of gastric mucosa， the levels of IL-8， IL-1β， TNF-α， ROS and MDA， relative expressions of HMGB1 and NF- κB mRNA， relative expressions of iNOS and HMGB1 protein and the phosphorylation level of NF-κB p65 were all increased significantly in model group （P＜0.05）； the epithelial cells of gastric mucosa in rats were incomplete in structure and decreased in the number， with an increase in cell fragments and vacuoles， and significant cell pyknosis. Compared with model group， the changes of the above indexes in GL groups and positive control group were significantly reversed （P＜0.05）； the changes in the above indicators in the GL high-dose group were more significant than GL low-dose and medium-dose groups （P＜0.05）； the pathological changes of gastric mucosal cells in rats had all improved. CONCLUSIONS GL may inhibit inflammation and oxidative stress by inhibiting the activation of HMGB1/NF-κB pathway， thus relieving HP-induced gastric mucosal injury.

Sleep Duration, Comorbidities, and Mortality in Korean Health Examinees: A Prospective Cohort Study / 예방의학회지

Objectives@#The association between long sleep duration and mortality is frequently attributed to the confounding influence of comorbidities. Nevertheless, past efforts to account for comorbidities have yielded inconsistent outcomes. The objective of this study was to evaluate this relationship using a large prospective cohort in Korea. @*Methods@#The study included 114 205 participants from the Health Examinees Study, who were followed for a median of 9.1 years. A composite comorbidity score was developed to summarize the effects of 21 diseases. Using Cox proportional hazards regression, hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cancer, and cardiovascular mortality associated with sleep duration were estimated. These estimates were adjusted for socio-demographic factors, lifestyle factors, body mass index, and comorbidity score. Additionally, a stratified analysis by subgroups with and without comorbidities was conducted. @*Results@#Throughout the follow-up period, 2675 deaths were recorded. After all adjustments, an association was observed between a sleep duration of 8 hours or more and all-cause mortality (HR, 1.10; 95% CI, 1.01 to 1.20). However, no such association was detected in the stratified analysis for the subgroups based on comorbidity status. @*Conclusions@#Long sleep duration was found to be associated with all-cause mortality among Koreans, even after adjusting for comorbidities. Additional studies are required to explore the mechanism underlying the association between sleep duration and major causes of mortality.

Impacts of isorhynchophylline on airway inflammation in asthmatic mice / 中国药房

OBJECTIVE To investigate the impacts of isorhynchophylline （IRN） on airway inflammation in asthmatic mice by regulating the monocyte chemotactic protein-1 （MCP-1）/CC chemokine receptor 2 （CCR2） signaling pathway. METHODS The asthmatic mice model was established by injecting and inhaling ovalbumin. The successfully modeled mice were randomly grouped into asthma group， IRN low-dose group （IRN-L， intragastric administration of 10 mg/kg IRN）， IRN high-dose group （IRN-H， intragastric administration of 20 mg/kg IRN）， IRN-H+CCL2 group [intragastric administration of 20 mg/kg IRN+intraperitoneal injection of 7.5 ng CC chemokine ligand 2 （CCL2）] and positive control group （intraperitoneal injection of 2 mg/kg dexamethasone）. The mice injected and inhaled with sterile phosphate-buffered solution were included in the blank control group， with 10 mice in each group. The mice in administration groups were given relevant medicine once a day， for consecutive 2 weeks. The levels of airway hyperreactivity indexes such as enhanced （Penh） value， tumor necrosis factor-α （TNF-α），interleukin-13 （IL-13） and IL-4 in serum， the number of eosinophil （EOS）， lymphocyte （LYM） and neutrophils （NEU） in alveolar lavage fluid and the protein expressions of MCP-1 and CCR2 in lung tissue were observed in each group； the pulmonary histopathological changes were observed， and inflammatory cell infiltration score was evaluated. RESULTS Compared with the blank control group， the infiltration of inflammatory cells in the lung tissue of mice was more significant in the asthma group， and there was swelling and shedding of cells； inflammatory infiltration score， Penh value， the levels of IL-4， IL-13 and TNF-α， the number of EOS， NEU and LYM， the protein expressions of MCP-1 and CCR2 were increased significantly （P＜0.05）. Compared with the asthma group， the pathological injuries of the IRN-L group， IRN-H group and positive control group were improved， and the above quantitative indexes were decreased significantly （P＜0.05）. Compared with the IRN-L group， the above quantitative indexes of the IRN-H group and positive control group were decreased significantly （P＜0.05）. There was no statistical significance in the above quantitative indexes between the IRN-H group and the positive control group （P＞0.05）. Compared with the IRN-H group， the above quantitative indexes of the IRN-H+CCL2 group were increased significantly （P＜0.05）. CCL2 reversed the protective effect of high-dose IRN on asthmatic mice. CONCLUSIONS IRN may reduce the release of airway inflammatory factors in asthmatic mice by inhibiting the activation of the MCP-1/CCR2 signaling pathway， so as to achieve the purpose of improving asthma.

Referral criteria of the SPOT Vision Screener for children under 6 years old / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To revise the referral criteria for the SPOT Vision Screener in children under 6 years old and assessed its accuracy based on the American Association for Pediatric Ophthalmology and Strabismus(AAPOS)uniform guidelines for instrument-based pediatric vision screen validation 2021.METHODS: Children who visited the Maternal and Child Health Center of Yuhuatai District in Nanjing city from January 2022 to April 2023 were included in the study and underwent SPOT refractive screening, cycloplegic retinoscopy, and other examinations. Abnormal children were defined according to AAPOS guidelines with amblyopia risk factors(ARFs)and visually significant refractive error(VSRE). Receiver operating characteristic(ROC)curve was used to calculate the optimal referral criteria and compared with manufacturer criteria, Wu's criteria, and Peterseim's criteria.RESULTS: A total of 959 children were examined, with 342 in the <4-year-old group and 617 in the ≥4-year-old group. The optimal referral criteria for the <4-year-old group were myopia ≤-2.75 D, hyperopia ≥+2.25 D, astigmatism ≤-2.75 D, and anisometropia ≥1.00 D. For the ≥4-year-old group, the criteria were myopia ≤-1.75 D, hyperopia ≥+2.00 D, astigmatism ≤-2.25 D, and anisometropia ≥1.00 D. The Youden index was 0.38 and 0.52, respectively, which were higher than other criteria.CONCLUSION: The use of new referral criteria for refractive screening in children under 6 years old demonstrates higher accuracy compared to previous criteria. It provides valuable guidance for pediatric eye care and vision health in children.

Relationship between eating out and overweight， obesity， and fatty liver disease in adult residents in a suburban area of Shanghai / 上海预防医学

ObjectiveTo investigate the prevalence of overweight， obesity and fatty liver disease （FLD） in adult residents in a suburban area of Shanghai， and to explore the relationship between these conditions and eating out of home （EOH）. MethodsAdult residents from Zhongshan Street， Songjiang， Shanghai， were invited to report their frequency of EOH and undergo a physical examination using B-ultrasonography from May to September 2017. Binary logistic regression analyses were conducted to examine the relationship between EOH and conditions of overweight， obesity， and FLD. ResultsAmong the final sample size of 6 608 participants， the prevalence rates of overweight， obesity， and FLD were 41.65%， 14.71% and 38.29%， respectively. After adjusting for potential confounders， logistic analyses revealed that participants with an EOH frequency > once/week had a 1.44-fold higher prevalence of obesity （P=0.006）， a 1.35-fold higher prevalence of overweight/obesity （P=0.005）， and a 1.36-fold higher prevalence of FLD （P=0.008）. ConclusionThe prevalence of overweight， obesity， and FLD is relatively high in Songjiang， Shanghai. EOH may be a risk factor for these diseases， and residents are recommended to reduce the frequency of EOH.

Efficacy and safety of fractional radiofrequency in treatment of acne scar / 中华医学美学美容杂志

Objective:To observe the efficacy and adverse reactions of fractional radiofrequency (FRF) in the treatment of facial acne scars.Methods:Fifty-seven patients with facial acne depressed scars were enrolled with the nature of Dreno scars as the diagnostic criteria. They were treated with lattice radiofrequency. The treatment heads were arranged in a matrix with a treatment area of 1.2 cm ×1.2 cm, an energy density of 80-100 mJ/pin, and an interval of five-seven once a week. And they were followed up and evaluated for the clinical efficacy and adverse reactions 6 months after the last treatment. Scoring was carried out according to the ECCA weight scores, and the efficacy judged according to complete improvement, significant improvement, moderate improvement, and mild improvement.Results:After 3 times of fractional radiofrequency treatment of 57 patients, the effective rate was 44 cases, accounting for 77.2%; the ECCA weight scores before and after treatment were 65.9±25.0 and 47.7±20.2, respectively; the difference was statistically significant ( t=13.92, P<0.001); At the same time of improvement, 32 cases of patients' complexion, fineness of pores, and skin elasticity had been improved to varying degrees, and patient satisfaction was high. Adverse reactions were mainly mild burning sensation, erythema and edema, and some patients had pale yellow exudate, etc, which could be relieved in 5-7 days. Conclusions:Fractional radiofrequency treatment of facial acne scars is safe and effective, with short recovery period, few adverse reactions and high patient satisfaction.

Effect of tert-butyl acetate and ethyl butyrate on the dissolution of gallbladder cholesterol stones / 中华肝胆外科杂志

Objective:To compare the effect and biotoxicity of tert-butyl acetate (TBA) and ethyl butyrate (EB) on stone dissolution in vitro.Methods:Ten gallstone samples from patients with multiple gallbladder stones were selected and the cholesterol content was analyzed by HPLC. Stone dissolution tests of TBA and EB were performed on cholesterol gallstone in vitro, and the weight of stone at each time point was recorded, meanwhile, methyl tert-butyl ether (MTBE) was used as the control. The inhibitory effects of MTBE, TBA and EB on proliferation of human normal liver cell line LO2 were analyzed by cell proliferation inhibition assay. Flow cytometry was used to analyze the effects of MTBE, TBA and EB on the early and late apoptosis of LO2 cells, and the changes of reactive oxygen species level in LO2 cells were also analyzed.Results:Of the 10 gallbladder gallstones, 6 were cholesterol gallstones and 4 were non-cholesterol gallstones. Stone dissolution experiment showed that the remaining stones of MTBE, TBA and EB groups were (47.83±3.84)%, (58.12±4.53)% and (75.75±4.61)% 30 minutes later. The remaining stones were (18.38±6.47)%, (33.82±6.22)% and (56.38±3.91)% 90 minutes later. MTBE had the best stone dissolution effect in vitro, the stone dissolution effect of TBA was slightly weaker than MTBE, and the stone dissolution effect of EB was relatively weak in all ( P<0.05). The cell proliferation inhibition experiment showed that the cell viability of the control group, MTBE group and TBA group were (100.00±4.46)%, (96.79±4.32)% and (93.72±3.51)%, respectively, and there were no significant differences among the three groups ( P>0.05). However, the cell viability of EB group (87.57±5.29)% was lower than the above three groups, and the differences were statistically significant ( P<0.001). The early apoptosis and late apoptosis of the control group were (1.67±0.15)% and (1.27±0.06)%, respectively. EB induced early apoptosis (15.90±0.53)% ( P<0.001) and late apoptosis (5.13±0.76)% ( P<0.05). However, MTBE and TBA had no significant effect on cell apoptosis ( P>0.05). Compared with control group, MTBE, TBA and EB all significantly inhibited the level of reactive oxygen species ( P<0.05), and the inhibitory effect of EB was the most obvious. Conclusions:TBA has good stone dissolution effect and biosafety for gallbladder cholesterol stones in vitro, while EB has relatively poor performance. TBA is a potential drug for gallstone dissolution.

An interpretation of AAPOS uniform guidelines for instrument-based pediatric vision screen validation 2021 / 中华实验眼科杂志

In January 2022, after an eight-year hiatus, the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) published the latest version of AAPOS uniform guidelines for instrument-based pediatric vision screen validation.Based on recent studies, the new guidelines have been updated and supplemented in many aspects, such as screening population, key points, methods and diagnosis criteria, including clinically significant refractive errors and myopia, simplified age subgroups, and adopted meridional refractive power.The updated guidelines will improve pediatric eye care, early detection of amblyopia and refractive screening, reduce excessive referral and ultimately improve the effectiveness of vision screening.In this article, the background and specific content of the updated guidelines were interpreted to guide clinical practice.

Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH) / 中华胃肠外科杂志

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

Risk analysis and suggestions of 570 drug wholesale enterprises in Hunan province / 中国药房

OBJECTIVE To provi de reference for standardizing the distribution behavior of drug wholesale enterprises and improving the supervision level of drug supervision departments. METHODS The defective items found in the on-site inspection of 570 drug wholesale enterprises in Hunan province in 2020 were summarized ，the main risks were analyzed to put forward countermeasures and suggestions. RESULTS & CONCLUSIONS The provincial drug regulatory departments conducted daily supervision and inspection among 192 drug wholesale enterprises ，of which 168 enterprises（87.50％）were ordered to make corrections；a total of 1 804 defective items were found ，involving 11 serious defects ，806 major defects and 987 general defects. The provincial drug regulatory departments conducted special inspections among 20 wholesale enterprises of narcotic drugs and psychotropic drugs ，of which 18 enterprises（90.00％）were ordered to make corrections ；a total of 48 defective items were found ， involving 33 major defects and 15 general defects ，and no serious defective items were found. The drug regulatory departments of all cities （autonomous prefectures ）inspected 358 drug wholesale enterprises ，of which 290 enterprises（81.00％）were ordered to make corrections ；a total of 1 499 defective items were found ，including 665 main defects and 834 general defects ，and no serious defective items were found. According to the statistics of occurrence frequency ，defective items of drug wholesale enterprises in Hunan province were mainly concentrated in storage and maintenance （687 items，20.50％），facilities and equipments （608 items， 18.14％），personnel and training （579 items，17.28％），receipt and acceptance （272 items，8.12％）and quality management system documents （260 items，7.76％），which together accounted for 71.80％ of the total defects. The main risks of drug wholesale enterprises included weak enterprise risk awareness ，high frequency of quality risks in drug marketing ，imperfect enterprise quality management system documents ，and fraud in enterprise business behavior. It is recommended that drug wholesale enterprises should establish quality risk management institutions ，evaluation standards and management systems ，improve the operation quality management system ，strengthen the management of drug storage ，standardize the operation and management of enterprises，strengthen personnel training and standardize procurement behavior ，so as to j ointly maintain the safety and efficacy of drugs and controllable quality.

Data Mining Study on Prescription Patterns of Different Dosage Forms of Chinese Herbal Medicines for Treating and Improving Immune-Inflammatory Indices in Patients with Rheumatoid Arthritis / 中国结合医学杂志

OBJECTIVE@#To explore the prescription patterns of different dosage forms of Chinese herbal medicines (CHMs) for the treatment of rheumatoid arthritis (RA) and their effects on immune-inflammatory indices.@*METHODS@#Clinical data were collected from patients with RA in 4 hospitals (3 Class A comprehensive hospitals and 1 Class B comprehensive hospital) in Anhui Province, China, from August 2012 to June 2018 via the electronic medical record gathering system. Following extraction of prescription information, each prescribed herb was quantified and standardized according to the knowledge base to establish a database of RA treatment formulae. The medical records were divided into the granules group and decoction pieces group. Core herbs and their combination patterns were obtained from the two groups of cases using Liquorice software. Changes in immune-inflammatory and hepatic and renal function indices were compared between the two groups using SPSS 23.0 software. The Aprior module of SPSS Clementine 11.1 software was applied to analyse the correlation between CHMs and improvement in indices. Finally, the ORACLE 10 g tool was used to evaluate the random walk model of the immune-inflammatory indices between the two groups.@*RESULTS@#(1) We retrospectively analysed 35,898 prescriptions for 6,829 patients with RA who received CHM treatment. There were 3,816 patients in the granules group and 3,013 in the decoction pieces group. (2) The core herbs were Pi (Spleen)-strengthening and dampness-resolving drugs, blood-activating and stasis-resolving drugs, wind/dampness-dispelling drugs and heat-clearing and detoxifying drugs. (3) Both dosage forms could improve immune-inflammatory indices in RA patients, with similar efficacy and no influence on hepatic or renal function. (4) Herba Siegesbeckiae and Oldenlandia had a stronger association with immune-inflammatory indices in the two groups. (5) The immune-inflammatory indices showed obvious improvement after treatment with granules and decoction pieces of CHMs, and there were long range correlations between the comprehensive evaluation indices and interventions.@*CONCLUSIONS@#The principal CHM treatment methods for RA in four hospitals in Anhui Province are strengthening Pi and resolving dampness, activating blood and resolving stasis, dispelling wind/dampness and clearing heat. Granules and decoction pieces of CHMs have similar efficacy in improving immune-inflammatory indices in RA patients and could be used as treatment options for RA.

Efficacy and safety of 308-nm SQ light-emitting diode light and 308-nm excimer light in the treatment of facial vitiligo: a retrospective study / 中华皮肤科杂志

Objective:To compare efficacy and safety of 308-nm SQ light-emitting diode (LED) light versus 308-nm excimer light in the treatment of facial vitiligo.Methods:Patients with stable facial vitiligo were retrospectively collected from Department of Physical Therapy, Hospital of Dermatology, Chinese Academy of Medical Sciences from June 2018 to June 2020, who received treatment with 308-nm SQ LED light (LED group) or 308-nm excimer light (excimer light group). The treatment was performed once or twice a week, and patients who had received more than 8 sessions of treatment were included in the analysis of efficacy and safety. Statistical analysis was carried out by using chi-square test.Results:Totally, 68 patients with 90 lesions were enrolled into the LED group, including 36 males and 32 females, aged 25.01 ± 13.37 years; 20 patients with 28 lesions were enrolled into the excimer light group, including 13 males and 7 females, aged 27.15 ± 14.30 years. After 8 and 16 sessions of treatment, there was no significant difference in the response rate between the LED group (23.33%, 46.67%, respectively) and excimer light group (14.29%, 46.43%, χ2 = 1.05, < 0.001, respectively, both P > 0.05). During the treatment, 36 (52.94%) patients in the LED group developed persistent erythema, 17 (85%) in the excimer light group developed persistent erythema or blisters. The incidence of adverse reactions was significantly lower in the LED group than in the excimer light group ( χ2 = 16.43, P < 0.001) . Conclusion:Compared with the 308-nm excimer light, the 308-nm SQ LED light showed similar effect but higher safety for the treatment of facial vitiligo.

Research on Anti-aging Guided by Qiluo Doctrine / 中国实验方剂学杂志

Along with increasing degree of population aging globally， senility， good health and long life have become the focus of the world. Guided by Qiluo doctrine， an essence， Qi and spirit theory is proposed as below， essence is the origin of life， Qi is the impetus of life and spirit is the embodiment of life. Based on holistic view of kidney deficiency involving the five internal organs and injuries of the five internal organs definitely affecting the kidney， a mechanism of aging is proposed as below， deficiency of kidney essence is the foundation of aging， deficiency of promordial Qi is the key of aging and physical and spiritual loss is the manifestation of aging. It provides a theoretical guidance for anti-aging study of rejuvenating the elderly and making the strong person stronger. By virtue of the experiences in kidney-tonifying medication accumulated for more than two thousand years， Bazi Bushen capsules has been developed， which has anti-aging efficacy， including tonifying kidney， replenishing essence， coordinating Yin and Yang， supplementing primordial Qi and nourishing body and spirit. Experimental researches have demonstrated that Bazi Bushen capsules can improve overall aging and systemic aging， as well as prevent and treat aging related diseases. Preliminary clinical studies demonstrate that this capsules can enhance athletic ability and improve sexual function， and is expected to become a representative Chinese patent medicine of anti-aging. This paper addresses aging and anti-aging on the basis of Qiluo doctrine， in the hope of helping prevention and treatment of aging related diseases.

Structure-based discovery of orally efficient inhibitors via unique interactions with H-pocket of PDE8 for the treatment of vascular dementia

Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC50 = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.

Cost-utility analysis of dexamethasone combined with bortezomib and lenalidomide in the treatment of newly diagnosed multiple myeloma / 中国药房

OBJECTIVE To eval uate the cost-util ity of regimen containing bortezomib in the treatment of newly diagnosed multiple myeloma in China. METHODS From the perspective of China ’s health system ，Markov model was constructed based on SWOG S 0777 clinical trial. The simulation time limit was 10 years，and the cycle was set with reference to the treatment cycle. Taking quality adjusted life years （QALYs）as the utility index ，the utility and cost were discounted at a discount rate of 5％；the willingness to pay （WTP）threshold was set to be 3 times of China ’s per capita gross domestic product （GDP）in 2021（242 928 yuan/QALY）. The incremental cost-utility ratio （ICER）of dexamethasone combined with bortezomib and lenalidomide （VRD） versus dexamethasone combined with lenalidomide （RD）were compared with cost-utility analysis. The sensitivity analysis was performed for the uncertainty of the model. RESULTS Results of baseline analysis showed that VRD regimen could obtain 0.65 more QALYs than RD scheme ，but its treatment cost was 135 782.77 yuan more than RD regimen ，ICER was 206 623.35 yuan/ QALY，which was lower than the WTP threshold set in this study ，VRD regimen was cost-effective. Single factor sensitivity analysis showed that the health utility value in progressive free survival had the greatest impact on the results ，the decrease of utility value would make the ICER higher than the WTP threshold ，and VRD regimen would no longer have advantages. Under the WTP threshold of 3 times of China ’s per capita GDP in 2021，the probability of VRD regimen being cost-effective was 86.5％； with the increase of WTP threshold ，the possibility of VRD regimen becoming more cost-effective than RD regimen would increase. CONCLUSIONS Under the WTP threshold of 3 times of China ’s per capita GDP in 2021，compared with RD regimen，VRD regimen is cost-effective in the treatment of newly diagnosed multiple myelo ma in China.

Construction and identification of a HEK293 cell line with stable TrxR1 overexpression / 南方医科大学学报

OBJECTIVE@#To construct a HEK293 cell line stably overexpressing TrxR1 as a cell model for functional study of TrxR1 and screening of TrxR1-targeting drugs.@*METHODS@#TrxR1 gene was amplified by PCR and ligated with the lentivirus expression vector pLVX-Puro, which was transformed into Escherichia coli and identified by Sanger dideoxy sequencing. HEK293 cells were infected with the recombinant lentivirus vector (pLVX-Puro-TXNRD1) and screened with Puromycin for cell clones with stable TrxR1 overexpression (HEK293-TrxR1-OE cells). HEK293-TrxR1-OE cells, along with HEK293 cells infected with pLVX-Puro vector (HEK293-NC) and normal HEK293 cells, were tested for mRNA and protein expression levels of TrxR1 using RT-qPCR and Western blotting. TrxR1 enzyme activity in the cells was evaluated with insulin endpoint assay and TRFS-green probe imaging. The sensitivity of the cells to auranofin, a specific TrxR1 inhibitor, was determined with CCK8 assay.@*RESULTS@#TrxR1 gene was successfully inserted into the lentiviral vector pLVX-Puro as confirmed by DNA sequencing. The enzyme activity and mRNA and protein expression levels of TrxR1 were significantly higher in HEK293-TrxR1-OE cells than in HEK293 and HEK293-NC cells (P < 0.005). The inhibitory effects of auranofin on proliferation and cellular TrxR1 enzyme activity were significantly attenuated in HEK293-TrxR1-OE cells as compared with HEK293 and HEK293-NC cells (P < 0.005).@*CONCLUSION@#We successfully obtained a HEK293 cell line with stable TrxR1 overexpression, which shows resistance to auranofin and can be used for screening TrxR1 targeting drugs.

Mechanism of Improvement Effects of Fupi Rougan Granules on Hepatic Fibrosis Model Rats / 中国药房

OBJECTIVE：To study the mechanism of improvement effects of Fupi rougan granule （FRG）on hepatic fibrosis model rats. METHODS ：The rats were randomly divided into blank group ，model group ，Colchicine tablet group （chemical positive control ，0.2 mg/kg），Fuzheng huayu capsule group （TCM positive control ，0.415 g/kg），FRG low-dose ，medium-dose and high-dose groups （20，40，80 g/kg），with 10 rats in each group ，except for 11 rats in blank group and model group （one rat was used to judge whether the modeling was successful ）. Except for blank group ，other groups were given intraperitoneal injection of 50％ CCl4 olive oil solution and intragastric administration of 30％ ethanol to induce hepatic fibrosis model. After modeling ， administration groups were given relevant medicine intragastrically ；blank group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 4 weeks. After last administration ，morphology changes of liver tissue in rats were observed. The serum levels of HA ，LN，PCⅢ and Col Ⅳ in rats were detected ，and protein expression of Beclin- 1 and LC3-Ⅱin liver tissue were also determined. mRNA and protein expression of Akt ，AMPK，mTOR，p70S6K were detected in liver tissues of rats. RESULTS ：Compared with blank group ，the structure of hepatic lobules in the model group was disordered ，the proliferation of fibrous tissue was obvious ，and some pseudolobules were formed ；the serum levels of HA ，LN，PCⅢ and Col Ⅳ， the protein expression of Beclin- 1 and LC 3-Ⅱ in liver tissue as well as mRNA and protein expression of Akt ，AMPK，mTOR and p70S6K were increased significantly （P＜0.01）. Compared with model group ，the liver injury of rats in FRG groups was significantly relieved ，and the levels of the above indexes in serum and liver tissue （except for LN and PC Ⅲ in FRG low-dose group） were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS ：FRG can improve hepatic fibrosis in rats ，the mechanism of which may be associated with down-regulating the expression of autophagy associated protein and Akt/AMPK/mTOR/ p70S6K signaling pathway related protein.

Role of Stromal Cell-Derived Factor-1 in Endothelial Progenitor Cell-Mediated Vascular Repair and Regeneration

Endothelial progenitor cells (EPCs) are immature endothelial cells that participate in vascular repair and postnatal neovascularization and provide a novel and promising therapy for the treatment of vascular disease. Studies in different animal models have shown that EPC mobilization through pharmacological agents and autologous EPC transplantation contribute to restoring blood supply and tissue regeneration after ischemic injury. However, these effects of the progenitor cells in clinical studies exhibit mixed results. The therapeutic efficacy of EPCs is closely associated with the number of the progenitor cells recruited into ischemic regions and their functional abilities and survival in injury tissues. In this review, we discussed the regulating role of stromal cell-derived factor-1 (also known CXCL12, SDF-1) in EPC mobilization, recruitment, homing, vascular repair and neovascularization, and analyzed the underlying machemisms of these functions. Application of SDF-1 to improve the regenerative function of EPCs following vascular injury was also discussed. SDF-1 plays a crucial role in mobilizing EPC from bone marrow into peripheral circulation, recruiting the progenitor cells to target tissue and protecting against cell death under pathological conditions; thus improve EPC regenerative capacity. SDF-1 are crucial for regulating EPC regenerative function, and provide a potential target for improve therapeutic efficacy of the progenitor cells in treatment of vascular disease.

One new coumarin from seeds of Herpetospermum pedunculosum / 中国中药杂志

This paper aims to investigate the chemical constituents of the seeds of Herpetospermum pedunculosum. One new coumarin and two known lignans were isolated from the ethanolic extract of the seeds of H. pedunculosum with thin layer chromatography(TLC), silica gel column chromatography, Sephedax LH-20 chromatography, Semi-preparative high performance liquid chromatography and recrystallization, etc. Their structures were elucidated as herpetolide H(1), phyllanglaucin B(2), and buddlenol E(3) by analysis of their physicochemical properties and spectral data. Among them, compound 1 was a new compound, and compounds 2 and 3 were isolated from this genus for the first time. In vitro anti-inflammatory activity test showed that herpetolide H had certain NO inhibitory activity for LPS-induced RAW 264.7 cells, with its IC_(50) value of(46.57±3.28) μmol·L~(-1).

Daylight photodynamic therapy for the treatment of actinic keratosis / 中华皮肤科杂志

Actinic keratosis (AK) is a kind of precancerous skin lesions related to long-term light exposure, and photodynamic therapy is one of its main treatment methods. Compared with conventional photodynamic therapy, daylight photodynamic therapy (DL-PDT) with daylight as a light source has advantages of more convenient operation, less pain and higher patient acceptability, but it is liable to be affected by weather and other factors. DL-PDT is suitable for the treatment of grade Ⅰ or Ⅱ AK on the head and face, and its efficacy may be affected by pretreatment, photosensitizers, irradiation dose, etc. This review mainly elaborates the advantages of DL-PDT and introduces its operation methods to help clinicians choose the best treatment protocol for AK.