ObjectiveTo investigate the effect of Yuejuwan on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice based on lipidomics， and to explore the potential pathways for improving lipid metabolism to prevent depression. MethodsSeven-week-old C57BL/6 mice were randomly divided into blank group， model group， Yuejuwan group（3.6 g·kg^-1） and fluoxetine group（10 mg·kg^-1）， and chronic unpredictable mild stress（CUMS） was used to establish the depression model. After 3 weeks of modeling， each administration group was gavaged with the corresponding drug solution according to the dose， and mice in the blank and model groups were given an equal volume of deionised water by gavage， one time/d for 2 weeks. After administration， the antidepressant effect of Yuejuwan was evaluated by neurobehavioral indices such as sucrose preference test， open field test， tail suspension test and forced swimming test. An automatic biochemical analyzer was used to measure contents of total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C）， high-density lipoprotein cholesterol（HDL-C）， aspartate aminotransferase（AST） and alanine aminotransferase（ALT） in mouse serum. Lipidomic analysis of mouse serum， prefrontal cortex and hippocampus was performed based on ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry（UPLC-LTQ-Orbitrap-MS）， and the expression of mammalian target of rapamycin（mTOR）， ribosomal protein S6 kinase（S6K）， phosphorylation（p）-mTOR， p-S6K in gastric tissues of mice was detected by Western blot. ResultsCompared with the blank group， mice in the model group exhibited significantly reduced sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly increased（P<0.01）， and serum levels of TC， TG， LDL-C， HDL-C， AST and ALT were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the Yuejuwan group showed a significant increase in the sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly reduced（P<0.01）， and the serum levels of TC， TG， LDL-C， AST and ALT were significantly decreased（P<0.05， P<0.01）. Lipidomic analysis revealed that Yuejuwan had a significant effect on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice， and The differential lipid metabolites were mainly enriched in the metabolic pathways of glycerophospholipid metabolism， sphingolipid signaling， and glycosylphosphatidylinositol-anchored protein biosynthesis， among which the glycerophospholipid metabolic pathway was the most significant. Western blot results showed that compared with the blank group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the model group were significantly increased（P<0.01）. In comparison with the model group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the Yuejuwan group were significantly decreased（P<0.01）. ConclusionThe intervention of Yuejuwan on lipid metabolism is one of the potential pathways for its antidepressant effect， which may be related to the regulation of mTOR/S6K signaling pathway upstream of lipid metabolism in the gastric tissues.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To compare the oncologic safety, surgical efficacy, and aesthetic outcomes between conventional breast-conserving surgery and axillary single-port incision insufflation endoscopic breast-conserving surgery with mini-latissimus dorsi surgery in early breast cancer patients. Methods A retrospective analysis of clinical data from 62 female patients with early breast cancer was performed. Patients were divided into two groups on the basis of surgical method: the conventional group (37 cases) and the endoscopic group (25 cases).The clinical baseline data, surgical results, and postoperative effects of the two groups were compared. Results According to the clinical baseline data, the endoscopic group had a greater maximum tumor diameter and a greater tumor-to-breast volume ratio due to expanded indications for breast-conserving surgery (P<0.001), whereas the other data revealed no statistically significant difference between the two groups (P>0.05). Compared with those in the conventional group, the total incision length in the endoscopic group was shorter [3.40(3.15, 3.60) cm vs. 7.30 (6.50, 7.60) cm, P<0.001], the postoperative drainage volume was lower (206.20±35.11 ml vs. 223.95±26.17 ml, P=0.026), but the operative time was longer (254.92±22.67 min vs. 146.78±13.01 min, P<0.001). The incision margin positive rate was 0% (0/25) in the endoscopic group, which was significantly lower than the 10.8% (4/37) in the conventional group (P=0.141). The endoscopic group had a lower incidence of complications (4% vs. 27%, P=0.047) and superior JBCS aesthetic scores at the 6-month follow-up (76% vs. 43.2%, P=0.006). Conclusion Axillary single-port incision insufflation endoscopic breast-conserving surgery with mini-latissimus dorsi surgery is not inferior to conventional procedures in terms of oncologic safety (margin-negative rate) and offers advantages in terms of scar concealment, fewer complications, and better aesthetic outcomes, especially suitable for early breast cancer patients with small-to-medium breast volumes, tumors located in the outer quadrants and mastectomy ratios of >20%.

ObjectiveTo explore the potential mechanism of Dingchuan Granule （定喘颗粒， DG） in the treatment of respiratory syncytial virus （RSV） pneumonia. MethodsA total of 60 male Sprague Dawley （SD） rats were randomly divided into control group， model group， ribavirin group， DG low-dose group， DG middle-dose group， and DG high-dose group， with 10 rats in each group. Except for the control group， rats were administrated with RSV via intranasal drip. After model establishment， the DG low-， middle-， and high-dose groups were administrated via oral gavage with DG at 3.47， 6.93， and 13.86 g/（kg·d） respectively， while the ribavirin group was administrated via oral gavage with ribavirin at 15.75 mg/（kg·d）. The drug was given once daily for one week. The rats in the control group and the model group were not given any drug， only subjected to the grasping action. Twenty-four hours after the last administration， the pathological changes of lung tissues were observed and scored using HE staining. The levels of serum inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）， were detected by colorimetry. The protein levels of nuclear factor （erythroid derived 2）-like 2 （Nrf2）， Kelch-like ECH-associated protein 1 （Keap1）， heme oxygenase 1 （HO-1）， and NAD（P）H quinone dehydrogenase 1 （NQO1） in lung tissues were measured by Western Blot. The RSV load as well as the gene expression levels of Nrf2， Keap1， HO-1， and NQO1 in lung tissues were determined by qRT-PCR. The level of reactive oxygen species （ROS） in rat lung tissues was detected using chemiluminescence. The levels of glutathione （GSH） and malondialdehyde （MDA） in rat lung tissues were measured by a microassay. ResultsCompared with the control group， other groups had significant increases in pathological score of lung tissue， RSV load， levels of ROS， MDA， serum TNF-α， IL-1β， and IL-6； decrease in GSH level， increases in expression level of Keap1 protein and its mRNA in lung tissue， and significant decrease in levels of Nrf2， HO-1， expression level of NQO1 protein and its mRNA （P＜0.05）. Compared with the model group， all the above-mentioned indicators in the DG low-， middle-， and high-dose groups and the ribavirin group were improved to varying degree （P＜0.05）. The levels of serum TNF-α， IL-1β， and IL-6 in rats of DG dose groups showed a dose-dependent pattern， the DG high-dose group exhibiting the best effect （P＜0.05）. The DG high-dose group was superior to the DG low- and middle-dose groups in reducing the levels of ROS and MDA， and increasing the level of GSH in lung tissues （P＜0.05）. The DG high-dose group and the ribavirin group had better effect than the DG middle-dose group in reducing the RSV load （P＜0.05）. The DG high-dose group was superior to the ribavirin group in improving the protein levels of Nrf2， Keap1， HO-1， and NQO1 （P＜0.05）. ConclusionDG could inhibit oxidative stress by regulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway to improve pulmonary inflammation and treat RSV pneumonia， with the DG high-dose group showing the best effect.

Objective: To analyze the timeliness of antir-etroviral therapy (ART) and its influencing factors among newly reported HIV/AIDS cases in Wenzhou City, Zhejiang Province from 2016 to 2023, so as to provide a reference for improving the ART effect of HIV/AIDS cases. Methods: Newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were selected as the research subjects. Demographic information, the situation of the first CD4+ T lymphocyte (CD4 cell) test, baseline CD4 cell count, and ART situation were collected through the Chinese Disease Prevention and Control Information System. The timely rate of ART was analyzed, and the influencing factors for timely ART among HIV/AIDS cases were analyzed using a multivariable logistic regression model. Results: A total of 4 500 newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were included, among which 3 679 were males, accounting for 81.76%, and 821 were females, accounting for 18.24%. The median age was 46.24 (interquartile range, 26.23) years. Among these cases, 3 606 received timely ART, with a timely rate of 80.13%. The timely rate of ART increased from 57.54% in 2016 to 91.97% in 2023 (P<0.05). Multivariable logistic regression analysis showed that unmarried/divorced/widowed (OR=0.769, 95%CI: 0.641-0.922), detainees (OR=0.492, 95%CI: 0.269-0.900), untimely first CD4 cell test (OR=0.278, 95%CI: 0.234-0.330), baseline CD4 cell count ≥200 cells/µL (OR=0.709, 95%CI: 0.595-0.843) or undetected (OR=0.131, 95%CI: 0.080-0.213) were associated with a lower timeliness for ART among HIV/AIDS cases. Conclusion From 2016 to 2023, the timely rate of ART among newly reported HIV/AIDS cases in Wenzhou City showed an upward trend, which was mainly affected by marital status, case source, timeliness of the first CD4 cell test, and baseline CD4 cell count.

Secondary organizing pneumonia after infection is a pathological condition characterized by connective tissue filling and obstructing the alveoli and bronchioles, in which following an infection in the lung, the inflammatory response is not controlled in a timely and effective manner. The pathogenesis and treatment of this condition can be interpreted through the Sanjiao membranous tube theory and the concept of stagnation within the pulmonary micro-membrane. Sanjiao is conceptualized as a four-way membranous tube that internally connects with the zangfu organs and externally with the skin and muscles, enabling the circulation of energy and fluids throughout the body. It also maintains communication with the zangfu micro-membranes. Within the lungs, the pulmonary micro-membrane is distributed and connected to the upper jiao membranous tube, facilitating the movement of qi and fluids and supporting nutrient distribution. External pathogens may invade the Sanjiao membranous system through the external membranous tube, travel internally along this system, and transform into latent pathogens that settle within the pulmonary micro-membrane. These latent pathogens can subsequently transform into heat or dampness, leading to the depletion of lung qi and impairing the lung′s ability to regulate and transport body fluids. Consequently, fluids may seep into the pulmonary micro-membrane, where they are transformed into dampness, turbidity, and phlegm. The accumulation of damp-turbidity and phlegm obstructs the flow of qi and blood, resulting in blood stasis in the pulmonary collaterals. This stagnation occurring within both the pulmonary micro-membrane and its associated collaterals underlies the development of secondary organizing pneumonia after infection. In severe cases, this condition may progress to pulmonary interstitial fibrosis. The therapeutic approach emphasizes expelling latent pathogens, regulating and dredging the pulmonary micro-membrane, tonifying the healthy qi, and supporting health. Regulating and dredging the pulmonary micro-membrane is a crucial step, with a focus on promoting the flow of lung qi, resolving dampness and phlegm, and activating blood circulation to remove stasis.

BACKGROUND: The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD). METHODS: We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships. RESULTS: The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages. CONCLUSIONS: Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit. REGISTRATION No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
Humans ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Dose-Response Relationship, Drug ; Randomized Controlled Trials as Topic

Following the release of the Technical Requirements on Quality Control and Standard Establishment of Traditional Chinese Medicine Formula Granules by the National Medical Products Administration in 2021, Chinese Pharmacopoeia Commission has promulgated 296 national drug standards so far, and most provinces have started the work of establishing provincial standards as supplements. The promulgation of standards fostered high-quality development of the industry. Since the implementation of national and provincial standards for more than three years, enterprises have gained deep understanding and hands-on experiences on the characteristics, technical requirements, production process, and quality control of traditional Chinese medicine(TCM) formula granules. Meanwhile, challenges have emerged restricting the high-quality development of this industry, including how to formulate quality control strategies for medicinal materials and decoction pieces, how to reduce manufacturing costs, and how to improve the pass rate and product stability under high standards. Based on the work experiences from standard management and process research, this article analyzed the distribution of sources, processing methods, dry extract rate ranges, process requirements for volatile oil-containing decoction pieces, control measures of safety indices, characteristics and trends of setting characteristic chromatograms or fingerprints, characteristics and trends of setting content ranges, and main differences between national standards and provincial standards. On the one hand, this article aims to present main characteristics for deeply understanding different indicators in standards and provide basic ideas for establishing quality and process control systems. On the other hand, from the perspective of industrial practice, suggestions are put forward on the important aspects that need to be focused on in the quality and process control of TCM formula granules.
Drugs, Chinese Herbal/chemistry* ; Quality Control ; Medicine, Chinese Traditional/standards* ; China ; Drug Industry/standards*