ObjectiveBased on traditional quality evaluation of Gardeniae Fructus（GF） recorded in historical materia medica， this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics， microscopic features， and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length， diameter and individual fruit weight of wild and cultivated GF， and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF， and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently， the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China， the starch content was measured by anthrone colorimetric method， the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method， the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection（HPLC-ELSD）， and the contents of representative components in them were measured by ultra-performance liquid chromatography（UPLC）. Finally， correlation analysis was conducted between quality traits and phenotypic traits， combined with multivariate statistical analysis methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， key differential components between wild and cultivated GF were screened. ResultsIn terms of traits， the wild GF fruits were smaller， exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger， displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF， while the blue-yellow value（b^*） of wild GF was significantly higher than that of cultivated GF. In the microstructure， the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals， while the endocarp contained stone cell class round， polygonal or tangential prolongation， undeveloped seeds were visible within the fruit. In contrast， the mesocarp of cultivated GF contained few calcium oxalate cluster crystals， or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like， with the innermost layer arranged in a grid pattern. Seeds were basically mature， and only a few immature seeds existed in some batches. Regarding primary metabolite content， wild GF exhibited significantly higher total polysaccharide level than cultivated GF（P<0.01）. In category-specific component content， wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF（P<0.01）. Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside， deacetyl asperulosidic acid methyl ester， gardenoside and chlorogenic acid compared to cultivated GF（P<0.01）. Conversely， the contents of genipin 1-gentiobioside， geniposide and genipin were significantly lower in wild GF（P<0.01）. ConclusionThere are significant differences between wild and cultivated GF in terms of traits， microstructure， and contents of primary and secondary metabolites. At present， the quality evaluation system of cultivated GF remains incomplete， and this study provides a reference for guiding the production of high-quality GF medicinal materials.

AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.

OBJECTIVE To evaluate the efficacy and safety of letermovir in preventing cytomegalovirus （CMV） infection after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. METHODS A retrospective cohort study was conducted， enrolling patients who underwent allo-HSCT at the Department of Hematology， Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine， from August 30， 2022， to February 21， 2024. Patients who initiated letermovir prophylaxis within 28 days post-transplantation were assigned to the experimental group （99 cases）， while those who did not initiate letermovir within this period were assigned to the control group （18 cases）. The incidence and clinical characteristics of CMV infection （including the number of wangranran@xinhuamed.com.cn CMV infection cases， the number of cases progressing to CMV disease， recurrent CMV disease， onset time of CMV infection， and treatment duration）， immune function recovery within 120 days post-transplantation， and the occurrence of transplantation-related complications （including CD4+ and CD8+ T-cell recovery， Epstein-Barr virus infection， acute graft-versus-host disease， human herpesvirus 6 infection， and posttransplant lymphoproliferative disorders） and adverse events were recorded. Univariate and multivariate Cox regression analyses were performed to identify factors influencing CMV infection. RESULTS A total of 117 patients were included， among whom 15 developed CMV infection， 5 progressed to CMV disease， and 2 experienced recurrent CMV disease. The CMV infection rate in the experimental group was significantly lower than that in the control group （P＜0.001）， and the onset time of CMV infection was significantly delayed （P＝0.014）. The proportion of patients with CD4+ T-cell counts ≥200 cells/μL in the experimental group was significantly lower than that in the control group （P＝0.022）. During the follow-up period， elevated creatinine levels were observed in 1 patient， and nausea and vomiting were observed in 2 patients. Multivariate Cox regression analysis revealed that the use of high-dose corticosteroids was a risk factor for CMV infection （HR＝6.230， 95%CI of 1.255-30.926， P＝0.025）， while initiating letermovir within 28 days post-transplantation was a protective factor （HR＝0.125， 95%CI of 0.045-0.348， P＜0.001）. CONCLUSIONS Early initiation of letermovir after allo-HSCT significantly reduces the CMV infection rate and delays the onset of infection， with favorable short-term safety.

Occupational chronic n-hexane poisoning incidents have been effectively curtailed in traditional printing and footwear industries, but its hazards are emerging in new industries. In recent years, two cluster incidents involving eight patients with occupational chronic n-hexane poisoning had occurred in Longgang District, Shenzhen City. Unlike the cleaning processes of electronic components in the electronics industry, these two incidents occurred during cleaning operations of non-electronic products. The rapid on-site detection tubes indicated the presence of n-hexane in the organic solvents used at the work site, and subsequent analysis of volatile components of the organic solvents further confirmed the involvement of n-hexane. Although the n-hexane exposure concentration of short term in the workplace air samples were below its occupational exposure limit, all eight cases were diagnosed as occupational chronic n-hexane poisoning, based on occupational exposure history, clinical manifestations, field investigations, and laboratory test results. These two poisoning incidents highlight that in air-conditioned or enclosed workshops with substandard occupational disease prevention facilities, the use of n-hexane containing organic solvents may result in occupational chronic n-hexane poisoning, even when the air monitoring results do not exceed the occupational exposure limits.

Mitochondria play a crucial role as organelles, managing several physiological processes such as redox balance, cell metabolism, and energy synthesis. Initially, the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria. Recent scholarly works, however, suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer. This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms. Specifically, we review the role of mitochondria transfer in regulating cellular metabolism restoration, excess reactive oxygen species (ROS) generation, proliferation, invasion, metastasis, mitophagy activation, mitochondrial DNA (mtDNA) inheritance, immune system modulation and therapeutic resistance in cancer. Additionally, we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To investigate the impact of Coronavirus Disease 2019 (COVID-19) on long-term renal function in patients with chronic kidney disease (CKD) who received no renal replacement therapy. Methods Thirty-nine CKD patients with an estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m²) at the time of COVID-19 diagnosis, admitted to Guizhou Aerospace Hospital from December 2022 to March 2023, were enrolled in the COVID-19 group. Additionally, 40 CKD patients without COVID-19 from September to December 2021, were included in control group. Changes in eGFR were compared between the two groups, and the temporal trend of eGFR in the COVID-19 group was analyzed using a mixed-effects linear model. Results No statistically significant differences were observed in eGFR levels at baseline, 1- and 3-month of follow-up between the COVID-19 and control groups (P>0.05). However, at 1 year of follow-up, the eGFR level in the COVID-19 group was significantly lower than that in the control group (P < 0.05). The mixed-effects linear model analysis revealed a decrease in eGFR by 1.84 mL/(min·1.73 m²) within 1 year of COVID-19 onset in the COVID-19 group, which inclined 4.62% from baseline, with the most significant decline (7.45%) observed among diabetic patients. Conclusion Patients with CKD who have not undergone renal replacement therapy experience a substantial decline in eGFR and worsened renal function within 1 year of COVID-19, necessitating close long-term renal function monitoring and timely interventions.

Objective To investigate the protective effect of curcumin (Cur) against arsenic-induced neuroimmune toxicity and the underlying molecular mechanisms in vivo. Methods Eighty SPF female C57BL/6 mice were randomly assigned to four groups: a control group, an arsenic-treated group, a Cur-treated group and an arsenic+Cur group, with 20 mice in each group. The control group received distilled water; the arsenic-treated group was given 50 mg/L NaAsO₂ in the drinking water; the Cur-treated group was gavaged with 200 mg/kg of curcumin for 45 days; and the arsenic+Cur group received distilled water and was gavaged with 200 mg/kg of curcumin. Y-maze and Morris water maze experiments were conducted to assess the learning and memory ability of the mice. Western blot analysis was used to detect protein levels of blood-brain barrier tight junction proteins zonula occludens protein 1(ZO-1) and claudin 5, T lymphocyte subpopulation CD4 and CD8, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related molecules JAK2 and STAT3. Real-time PCR was used to assess the mRNA levels of CD4⁺ T lymphocyte subsets type 1 T helper (Th1), Th2, Th17 and regulatory T cells (Treg) transcription factors and cytokines in hippocampus. Results Compared with the control group, the arsenic-treated group showed a significantly decreased correct rate, increased latency to reach the platform on the third and fifth days, and reduced times of crossing the platform. The expression of ZO-1 and claudin 5 protein decreased significantly, and the protein levels of CD4 and CD8 were up-regulated. The mRNA levels of Th1, Th17, and Treg transcription factor T-box expressed in T cell(T-bet), retinoid-related orphan receptor gamma t(RORγt), and forkhead box protein 3(FOXP3) in the arsenic-treated group were decreased. Th1 and Th17 cytokines interferon γ(IFN-γ) and interleukin 17(IL-17) were markedly decreased. In contrast, the mRNA levels of the Th2 transcription factor GATA binding protein 3(GATA3) and cytokine IL-4 in arsenic-treated group were higher than those in the control group. Furthermore, the protein levels of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) increased. Compared with the arsenic-treated group, the arsenic+Cur group demonstrated a significantly increased correct rate, decreased latency to reach the platform on the third and fifth days, and increased times of crossing the platform. The protein expression levels of ZO-1 and claudin 5 increased significantly, and the protein levels of CD4 and CD8 were down-regulated. The mRNA levels of Th2 transcription factor GATA3 and cytokine IL-4 were decreased. The mRNA levels of Th17 transcription factor RORγt and cytokine IL-17 were markedly increased. Furthermore, the protein levels of p-JAK2 and p-STAT3 decreased. Conclusion Through inhibiting the JAK2/STAT3 signaling pathway, curcumin could improve arsenic-induced decline in learning and memory abilities in mice, reverse the destruction of blood-brain barrier permeability of innate immune system components in arsenic-exposed mice, and antagonize arsenic-induced increase in the number of renal CD4 and CD8 molecule as well as the imbalance of CD4⁺ T lymphocyte subsets (Th1, Th2, Th17 and Treg), ultimately counteracting arsenic-induced neurotoxicity.
Animals ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Female ; Curcumin/pharmacology* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Mice ; Arsenic/toxicity*

Objective:To investigate the effectiveness of abdominal compression in tumor motion and the target volume, and analyze the suitable margins of planning target volume (PTV) for patients treated with lung-SBRT based on 4DCT.Methods:Patients diagnosed with peripheral pulmonary tumor were enrolled. The patients were divided into the whole group, upper-middle-lobe group (group A) and the lower-lobe group (group B). Each patient underwent 3DCT, 4DCT with abdominal compression (4DCT com) and 4DCT with free breath (4DCT free) scans. The GTVs were delineated and IGTVs on these images. PTV MIP 5 mm, PTV MIP 4 mm, PTV MIP 3 mm were constructed with a 5, 4, 3 mm margin in left-right (LR), anterior-posterior (AP) directions and cranial-caudal (CC) directions. Results:The median motion vector with compression reduced by 30.92% in whole group, increased by 3.42% in group A and reduced by 18.80% in group B, respectively. And there were no significant differences of TMA LR, TMA AP, TMA CC and motion vector by the Wilcoxon test ( P>0.05). The median sizes of IGTV MIP com , IGTV MIP free and IGTV10 com, IGTV10 free were 4.01, 5.36 cm 3and 6.59, 7.65 cm 3, with statistically significant difference ( Z=-3.45, -3.14, P<0.01). The median ratio of DI of IGTV CBCT com in PTV MIP 5 mm, PTV MIP 4 mm and PTV MIP 3 mm≥95% was 100%, 100% and 83.33%, respectively. Conclusions:The patients′ respiratory pattern changed with abdominal compression and abdominal compression is useful in reducing the size of IGTV MIP and IGTV10, which could reduce the target volume and protect the normal tissue. Adding a 4 mm margin to IGTV MIP com based on 4DCT account for respiration in SBRT is a tendency for precise radiotherapy.

Objective:To explore the effectiveness and feasibility of the machine learning models based on radiomics in the diagnosis of pituitary prolactin macroadenoma.Methods:Totally 122 histologically proven pituitary macroadenoma patients, including 70 cases of pituitary prolactin macroadenoma (PPM) and 52 cases of non-pituitary prolactin macroadenoma (NPPM), were retrospectively recruited. The differences of age, sex, serum prolactin value, bleeding, cystic degeneration and Knosp classification were compared between PPM and NPPM. The pre-processing, delineation of the region of interest and feature extraction of the preoperative axial contrast-enhanced T 1WI image were performed in the 3Dslicer software. The optimal feature set were selected by least absolute shrinkage and selection operator. All patients were randomly divided into the training group ( n=85) and the test group ( n=37) at a ratio of 7∶3. The models were established in the training group by logistic regression and support vector machine (SVM), and then verified by the test group. ROC curves were drawn respectively, and specificity, sensitivity, accuracy and area under the ROC curve (AUC) were calculated. Results:The age [(38±12) years vs . (43±11) years], gender ratio (male/female 50 cases/20 cases vs . 14 cases/38 cases) and prolactin value [366.00 (117.75, 1 156.25)μg/L vs . 47.25 (32.68, 62.40) μg/L] of patients with PPM and NPPM were statistically different ( P<0.05). The AUC values of logistic regression and SVM in the training group were 0.936 and 0.946, and the AUC values of the test group were 0.768 and 0.774, respectively. The diagnostic accuracy of logistic regression and SVM in the training group were 88.2% and 91.8%, and the accuracy of the test group were 73.0% and 77.8%. Conclusion:The machine learning models based on the radiomics can predict the pituitary prolactin macroadenoma well with a high accuracy.