ObjectiveTo observe the mechanism of chronic psychological stress aggravating idiopathic pulmonary fibrosis （IPF） in rats and the regulatory effect of Xiaoyaosan. MethodSixty SD rats were acclimatized for one week and then randomly divided into five groups： sham operation group， IPF group， IPF and depression model group， pirfenidone group， and pirfenidone + Xiaoyaosan group， with 12 rats in each group. The IPF group was induced by intratracheal instillation of bleomycin （5 mg·kg^-1） and administered 0.9% sodium chloride solution intragastrically. The model group was induced with bleomycin （5 mg·kg^-1） combined with chronic unpredictable mild stress to establish a rat model of IPF and depression and administered 0.9% sodium chloride solution intragastrically. Concurrently， the pirfenidone group was administered pirfenidone aqueous solution （50 mg·kg^-1） intragastrically， and the pirfenidone + Xiaoyaosan group was administered pirfenidone aqueous solution （50 mg·kg^-1） and Xiaoyaosan decoction （19.27 g·kg^-1） intragastrically. The experiment lasted for four weeks. Various parameters， including body weight， food intake， sucrose consumption rate， open field behavior， lung function， lung coefficient， pathological changes in lung tissue， and hydroxyproline （HYP） content were compared among the groups. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum cortisol （CORT）， corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH） levels， and serotonin （5-HT） levels in serum and hippocampus. The levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in serum and lung tissue were also measured. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA expression of IL-1β， TNF-α， IL-6， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear transcription factor-κB p65 （NF-κB p65） in lung tissue. Western blot was used to detect the expression of proteins related to the p38 MAPK/NF-κB signaling pathway. ResultCompared with the normal group， IPF and depression model group showed slow weight gain， reduced food intake， decreased sucrose consumption rate， reduced total distance and average speed of movement in the open field test， weakened lung function， increased lung coefficient （P<0.01）， significant inflammatory cell infiltration in lung tissue by hematoxylin-eosin （HE） staining， collagen fiber deposition by Masson staining， and increased HYP content （P<0.01）. There were elevated levels of serum CORT， CRH， and ACTH （P<0.05， P<0.01）， increased protein and mRNA levels of IL-1β， IL-6， and TNF-α in serum and lung tissue， decreased 5-HT levels in serum and hippocampus， and increased relative expression of p-p38 MAPK and p-NF-κB p65 proteins in lung tissue （P<0.01）. Compared with the IPF and depression model group， the depression and IPF of rats in the pirfenidone + Xiaoyaosan group were effectively ameliorated， as evidenced by faster weight gain， increased food intake and sucrose consumption rate， increased total distance and average speed of movement in the open field test， enhanced lung function， reduced lung coefficient （P<0.01）， decreased inflammatory cell infiltration by HE staining， reduced collagen fiber deposition by Masson staining in lung tissue， and decreased HYP content （P<0.01）. Decreased serum CORT， CRH， and ACTH levels （P<0.05， P<0.01）， decreased protein and mRNA levels of IL-1β， IL-6， and TNF-α in serum and lung tissue （P<0.05， P<0.01）， increased 5-HT levels in serum and hippocampus （P<0.05， P<0.01）， and decreased relative expression of p-p38 MAPK and p-NF-κB p65 proteins in lung tissue were also noted （P<0.05， P<0.01）， with the effects of Xiaoyaosan + pirfenidone being more significant. ConclusionChronic unpredictable stress exacerbates the progression of IPF in rats. The combination of Xiaoyaosan and pirfenidone not only improves depressive-like behavior but also alleviates pulmonary fibrosis， potentially through the regulation of the p38 MAPK/NF-κB signaling pathway and inhibition of excessive expression of inflammatory factors.

Tripterygium wilfordii is widely used in the treatment of immune system disease and has a remarkable curative effect. Triptolide and Tripterygium glycosides are the most commonly used active ingredients in clinical practice， but their treatment window is narrow and there are many side effects. The damage involves the reproductive system， blood system， cardiovascular system， digestive system， etc. Based on clinical observations and literature summaries， the symptoms of adverse reactions mostly occur in the digestive system （liver and gastrointestinal tract）. Relevant scholars have launched a lot of studies of the manifestations of liver injury induced by T. wilfordii and the mechanism of liver injury. The mechanism is mainly related to liver cell apoptosis， induction of oxidative stress， immune injury， excessive autophagy of liver cells， abnormal fatty acid metabolism， and abnormal enzyme metabolism in liver tissues. This article reviewed and summarized relevant literature on gastrointestinal injury caused by T. wilfordii， but there are few studies on the manifestations and mechanisms of adverse reactions， which still need further research by scholars. In addition， this article also summarized the research on how to reduce toxicity and enhance efficacy of prescriptions prepared from T. wilfordii in the digestive system， mainly involving compatibility with western medicines （Methotrexate， Leflunomide， Iguratimod， etc.）， use along or combination with Chinese medicines （single Chinese medicine， Chinese medicine monomers， and Chinese medicine compounds）， acupuncture and moxibustion （electroacupuncture and moxibustion）， dosage form improvement （glycol plastid gel， self-dissolving microneedle， solid lipid nanoparticles， gastric floating sustained-release capsules， etc.）， processing （steaming， stir-frying， radish seed processing， money grass processing， licorice processing， etc.）， and other methods to reduce toxicity. To sum up， this article analyzed the manifestations， mechanisms， and methods of reducing toxicity and enhancing efficacy of T. wilfordii-induced liver injury and gastrointestinal injury by sorting out relevant literature， in order to provide a reference for the clinical application of T. wilfordii and some research ideas for the future in-depth study of T. wilfordii-induced digestive system injury.

Objective To explore risk factors of early lung infection after liver transplantation and to construct a prediction model of early lung infection after liver transplantation.Methods The clinical data of 269 patients who underwent orthotopic liver transplantation for the first time were retrospectively analyzed.Patients were divided into the infected group(n=97)and the non-infected group(n=172)according to whether pulmonary infection occurred within 30 days after operation.The preoperative general data,preoperative laboratory examination results,intraoperative and postoperative data of the patients were collected.Multivariate Logistic regression analysis were used to screen risk factors of pulmonary infection.Based on the results of multivariate analysis,the prediction model was constructed and the prediction efficiency of the model was evaluated.Results Univariate and multivariate Logistic regression analysis showed that preoperative PNI≤41.70(OR=1.972,95%CI:1.047-3.714,P=0.036),LMR≤1.52(OR=2.020,95%CI:1.102-3.705,P=0.023),MELD score＞10.72(OR=1.985,95%CI:1.103-3.573,P=0.022),operative time＞448.00 min(OR=2.676,95%CI:1.515-4.727,P=0.001)and intensive care unit(ICU)hospitalization time＞4.0 days(OR=2.623,95%CI:1.335-5.154,P=0.005)were independent risk factors for early pulmonary infection after liver transplantation.The ROC area under the curve(AUC)of the prediction model based on the results of multivariate Logistic regression analysis was 0.768,the sensitivity was 80.41%and the specificity was 60.47%.Conclusion The prediction model based on PNI,LMR,MELD score,operation time and ICU hospitalization time can effectively predict the occurrence of early pulmonary infection after liver transplantation.

Background Climate change has resulted in long-term impacts on human health. Implementing efficient adaptation strategies among primary healthcare facilities is well determined by whether staff of different genders recognize the health risks related to climate change and are willing to take active measures. Objective To investigate gender differences on perceptions of health risks and attitude towards adaptation strategies among primary healthcare workers in China, and provide relevant suggestions. Methods By adopting a multi-stage cluster sampling method, we selected 21 urban and 10 rural healthcare facilities in Guangdong Province to collect information with a questionnaire. Then chi-square test, Wilcoxon rank sum test, and logistic regression analysis were used to explore the gender differences in climate change-related health risk cognition, knowledge acquisition channels, attitudes towards adaptation strategies, main obstacles, and resource requirements among the healthcare workers. Results Of 733 participants, 38.47% (282 participants) were male and 61.53% (451 participants) were female. The percentages of male healthcare workers who agreed that climate change is happening and recognized the causes of climate change (70.21%, 60.99%) were higher than the percentages of female counterparts (59.87%, 49.00%) (both Ps＜0.05), but no obvious gender differences existed in recognizing health risks of heatwaves and infectious diseases as well as sensitive population identification (all Ps＞0.05). Most of the participants (92.50%) received climate change and health-related information from mass media like TV, radio, and newspapers. Meanwhile less men chose new media channels than women (OR=0.62, 95%CI∶ 0.41-0.94). Only 30.56% of the participants (33.69% of men and 28.60% of women) reported involvement of relevant training and lectures. Most of them (90.96%) agreed to take active measures to deal with the health threats associated with climate change without gender differences for various measures (all Ps＞0.05). The leading obstacles were hard to integrate health adaptation to climate change into main work of institutions (most female agreed, 72.28%) and the lack of funds (most male agreed, 77.66%). Increasing funding for primary health care was regarded as the most needed resource by male (86.88%) and female (89.14%). After controlling the influence of other social factors, more men agreed with the lack of funds than women (OR=1.57, 95%CI∶ 1.10-2.24). Conclusion There are some gender differences in the perceptions of health risks and adaptation strategies of climate change among primary healthcare workers: Male staff are more likely to agree with climate change and regard the lack of funds as the main obstacle, while women prefer to choose new media channels to obtain information. It’s suggested that the government and relevant institutions focus on the learning and training of climate change and health-related knowledge and expand diversified information access, and promote capacity building to cope with health threats at grass-root level, in the light of recognized gender differences among primary healthcare workers.

Xiaoyaosan， a classical prescription for mental disorder recorded in Formulary of the Bureau of Taiping People's Welfare Pharmacy（《太平惠民合剂局方》）， is composed of Bupleuri Radix， Angelicae Sinensis Radix， Paeoniae Radix Alba， Atractylodis Macrocephalae Rhizoma， Poria， Zingiberis Rhizoma Praeparatum， Menthae Haplocalycis Herba， and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle. Clinical practices and experiments have proved that it can be used for primary depression， anxiety， as well as the depression induced by various somatic disorders， such as gynecological diseases， internal diseases， and digestive system diseases， as evidenced the improvement of Hamilton depression rating scale score， self-rating depression scale score， etc. Xiaoyaosan has been verified to be remarkably effective， with high compliance and no obvious adverse reactions in patients. Xiaoyaosan mainly acts on monoamine neurotransmitters 5-hydroxytryptamine （5-HT）， norepinephrine （NE）， and dopamine （DA）， adrenocorticotropic hormone （ACTH） and corticosterone （CORT） in hypothalamic-pituitary-adrenal axis， pro-inflammatory cytokines interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factored （TNF）-α， and orexin， ghrelin， and leptin in intestinal microecology and brain-gut axis， to regulate the neurobiochemical mechanism， endocrine mechanism， immune mechanism， and abnormal brain structure， thereby preventing and alleviating depression. However， the antidepressant mechanism of Xiaoyaosan needs to be further discussed. Through literature research， this paper analyzes the clinical application and basic mechanism of Xiaoyaosan in the treatment of depression， which is expected to serve as a reference for the application of this prescription in the clinical prevention and treatment of depression and improvement of the quality of life of patients， and further research on the antidepressant mechanism of Xiaoyaosan.

Objective:To investigate the effect of lncRNA HOTTIP on the radiosensitivity of four non-small cell lung cancer cell lines cultured in vitro by regulating the expression of miR-663a. Methods:Four non-small cell lung cancer cell lines (H838, H157, A549, and H1299) were irradiated with different radiation intensities (0, 2, 4, 6, and 8 Gy). Cell survival was detected by colony formation assay. The expression levels of HOTTIP and miR-663a were detected by qRT-PCR. A549 and H1299 cells were selected for the subsequent experiment. After silencing HOTTIP and/or over-expressing miR-663a, cell survival was detected by colony formation assay. Cell apoptosis was detected by flow cytometry. The expression levels of Cleaved caspase-3, Cleaved PARP andγ-H 2AX were quantitatively measured by Western blot. The targeting relationship between HOTTIP and miR-663a was vefiried by dual luciferase reporter assay and qRT-PCR. Results:The expression of HOTTIP was up-regulated, whereas that of miR-663a was down-regulated in the radiation-resistant H157, A549 and H1299 cells. Silencing HOTTIP or over-expressing miR-663a inhibited the survival of A549 and H1299 cells (radiosensitization ratios were 1.562 and 1.507, respectively), promoted the expression of Cleaved caspase-3, Cleaved PARP and γ-H 2AX, and accelerated cell apoptosis induced by radiation exposure. miR-663a was a target gene of HOTTIP, and HOTTIP negatively regulated the expression of miR-663a. The inhibition of miR-663a reversed the effect of silencing HOTTIP on the radiosensitivity of non-small cell lung cancer cells. Conclusion:Silencing HOTTIP can suppress the survival of non-small cell lung cancer cells and promotes cell apoptosis by up-regulating the expression of miR-663a, thereby enhancing the radiosensitivity of non-small cell lung cancer cell lines.

Objective:The aim of this study was to compare the efficacy and safety of iguratimod (IGU) or leflnomide (LEF) in combination with methotrexate (MTX) in patients with active rheumatoid arthritis (RA).Methods:This was a multicenter, randomized, double-blinded, double dummy and controlled clinical trial. Patients with moderate or high active RA were randomized in a 1∶1 ratio to receive IGU+MTX (Group A) or LEF+MTX (Group B) treatment. The efficacy and safety were assessed at week 12, 24 and 52, respectively. The primary endpoint was the American Colleague of Rheumatology 20 (ACR20) response rates at the 52th week. Pearson chi square test and two-way Analysis of Variance (ANOVA) were used to compare the improve- ment of ACR20 and DAS28 at 52 weeks. Pearson chi square test or Fisher exact probability test were used to compare the ACR 20 and ACR70 rate between the two groups after treatment. The measurement data of the two groups were compared by independent sample t-test or nonparametric test. Results:A total of 240 RA patients were enrolled in the present study. As a result, 84.1% and 81.0% of patients achieved ACR20 criteria at the 52th week in Group A and Group B, respectively ( χ2=0.35, P=0.56). And the ACR50/70 response rates, disease activity score 28 (DAS28), simplified disease activity index (SDAI) and the absolute decrease of DAS28 from baseline were not statistically different between the two groups at week 12, 24 and 52. The rates of adverse events were lower in Group A than those in Group B (60.0% vs 79.0%, P<0.01). The elevations of glutamic pyruvic transaminase/glutamic oxalacetic transaminase levels, concomitant use of hepatinica and white blood cell decrease were more common in Group B ( P<0.05). Conclusion:IGU in combination with MTX is an efficacious and safe treatment regimen, which is comparable in efficacy in control active RA but superior in safety to LEF combined with MTX.

Objective:To explore the evolution of imaging findings on dynamic chest high resolution CT（HRCT） in patients with mild COVID-19.Methods:The data of epidemiology, clinical data and continuous dynamic chest high-resolution CT images of the patients with mild COVID-19 were analyzed retrospectively. Twenty-five patients (including 24 common type and 1 mild) were enrolled in the group, including 14 males and 11 females, with age of （42±12） years and hospital stay of （19±5） days. The basic images and dynamic images of HRCT were analyzed and compared by the radiologists.Results:The clinical manifestations were fever (22 cases), cough (18 cases), expectoration (8 cases), pharyngeal pain (6 cases). Most laboratory tests lacked specificity. There were no significant abnormalities on chest CT of one mild patient. HRCT findings of the common type were as follows: (1) the distribution of the lesions: most of the multiple lesions involved both lungs (19 cases), with average of 3 (3±1) lobes, located in the peripheral pulmonary zone near the pleura (22 cases); (2) the morphology and density of the lesions: most of the lesions were ground glass density foci (22 cases), which were patchy and massive (18 cases), nodular (10 cases) and arc broadband (7 cases); with the development of the disease, the density of some lesions increased with localized pulmonary consolidation (10 cases), accompanied by air bronchus sign (5 cases) and halo sign (5 cases). Dynamic changes of HRCT images in the chest: the positive manifestations were found on the 5th (5, 6) day after the onset of the disease, the progressive time of CT lesions was 5 (5, 7) days, the peak time of CT lesions was 11 (10, 13) days, and the turning time of CT lesions was 9 (8, 11) days.Conclusions:Dynamic chest HRCT can monitor the basic evolution process of the disease in patients with mild COVID-19, and provide a more intuitive basis for clinical early diagnosis and treatment.

Objective To evaluate the efficacy and safety of modified transurethral plasmakinetic enucleation of prostate (M-TPEP) combined with cystolithectomy in elderly patients with high risk of large volume benign prostatic hyperplasia (BPH) complicated with large urinary bladder calculi. Methods Seventy-one patients with high risk of large volume BPH complicated with large urinary bladder calculi were selected, and the patients were treated with M-TPEP combined with cystolithectomy. The operation time, intraoperative blood loss, hospitalization time, complications, and the maximum urinary flow rate (Qmax), post-void residual volume (PVR), serum potassium, international prostate symptom score (IPSS), quality of life (QOL) score preoperative and postoperative 3 months were recorded. Results Seventy-one patients successfully completed the operation, and no death occurred. The operation time was (75.48 ± 6.51) min, intraoperative blood loss was (82.63 ± 10.08) ml, and postoperative hospitalization time was 5-7 d. Incidence of intraoperative capsule perforation was 2.82% (2/71), incidence of postoperative temporary urinary incontinence was 7.04% (5/71), incidence of urethral and bladder irritation after operation was 8.45% (6/71), and incidence of postoperative wound infection was 2.82% (2/71). The PVR, IPSS and QOL score 3 months after operation were significantly lower than those before operation: (6.89 ± 0.74) ml vs. (205.13 ± 40.08) ml, (2.71 ± 0.45) scores vs. (28.62 ± 3.57) scores and (1.36 ± 0.24) scores vs. (4.93 ± 0.38) scores, the Qmaxwas significantly higher than that before operation: (22.46 ± 2.97) ml/s vs. (5.24 ± 0.43) ml/s, and there were statistical differences (P＜0.01);there was no statistical difference in serum potassium between before operation and 3 months after operation (P＞0.05). Conclusions M-TPEP combined with cystolithectomy has short operation time, quick recovery after operation and low complication rate. It is a proper operative method for the elderly patients with high risk of large volume BPH and large urinary bladder calculi.

Objective To evaluate the safety and drug adherence of tocilizumab(TCZ)in patients with moderate to severe rheumatoid arthritis(RA)in routine clinical practice. Methods This 24 week single center observational study recruited patients with moderate to severe RA. Therapy adherence rate was calculated by actual dosing/expected dosing×100%. Efficacy end points included physician global assessment of disease activity(PGA),patient global assessment of disease activity(PtGA),28-joint disease activity score(DAS28)and so on. Safety was evaluated by recorded adverse events (AEs). Results Sixty patients were enrolled with a mean (SD) treatment adherence of (67±27)%. PGA, PtGA, pain assessment (VAS), TJC and SJC all decreased during this study. At the 12th week, 25%(6/24) and 29%(7/24) of the patients achieved DAS28 remission and EULAR good response,respectively.Eighteen AEs were recorded,of which only 2 were severe AEs(SAEs)and neither was related to TCZ. Conclusion TCZ is a highly safe treatment for decreasing disease activity in patients with moderate to severe RA in China.However,drug adherence still need to be improved.