Objective To investigate the palmitoyltransferase (PATs) activity during different developmental stages of Plasmodium falciparum and to explore the impact of PATs activity on intra-erythrocytic replication and gametocytogenesis, so as to provide insights into development of novel antimalarial targets. Methods The PATs activity was measured using the click chemistry method during different developmental stages of P. falciparum, including rings, trophozoites, schizonts, and gametocytes. P. falciparum-infected erythrocytes were divided into three groups, including a control group, a dimethyl sulfoxide (DMSO) group, and a 2-bromopalmitate (2-BP) group. Erythrocytes in the control group were incubated in normal culture media, and cells in DMSO and 2-BP groups were exposed to DMSO or 2-BP at a final concentration of 10 μmol/L to examine the inhibitory effect of 2BP on the PATs activity. The growth curve analysis and gametocyte production assay were employed to investigate changes in asexual proliferation and gametocyte production of P. falciparum following inhibition of the PATs activity with 2-BP, and transcriptomics sequencing was performed to examine the impact of inhibition of the PATs activity with 2-BP on transcriptional levels of P. falciparum and possible mechanisms. Results The green fluorescence intensity of PATs varied across developmental stages of P. falciparum (F = 38.120, P < 0.001), with a higher fluorescence intensity seen in trophozoites (35.680 ± 8.439), merozoites (33.380 ± 9.030) and gametocytes (21.540 ± 8.654), and a lower intensity in ring bodies (10.720 ± 3.183) (all P values < 0.05). The green fluorescence intensities were 8.738 ± 1.576, 8.633 ± 1.827 and 4.911 ± 0.318 in the control group, DMSO group, and 2-BP group 4 days post-culture (schizont stage), respectively (F = 91.490, P < 0.001), and the PATs activity was significantly inhibited post-treatment with 2-BP (P < 0.05). The areas under the time curve for the parasitemias were 25.700 ± 0.696, 28.630 ± 3.062 and 8.370 ± 1.751 in the control group, DMSO group, and 2-BP group following inhibition of the PATs activity during the asexual stage of P. falciparum (F = 83.440, P < 0.001), and the parasitemia was lower in the 2-BP group than in the control group and the DMSO group (both P values < 0.001). In addition, the asexual stage development was delayed in the 2BP group, with abnormal morphology seen. The numbers of merozoites were 18.050 ± 4.362, 18.200 ± 3.517 and 14.020 ± 4.320 in each schizont in the control group, DMSO group and 2-BP group, respectively (H = 39.100, P < 0.001), and the merozoite number was significantly lower in the 2-BP group than in the control group and the DMSO group (both P_adjusted values < 0.001). The areas under the time curve for P. falciparum gametocyte production were 18.900 ± 0.384, 18.240 ± 0.177 and 7.507 ± 0.201 in the control group, the DMSO group, and the 2-BP group following inhibition of the PATs activity, respectively (F = 1 677.000, P < 0.001), and the proportion of gametocyte production was statistically lower in the 2-BP group than in the control group and DMSO group (both P values < 0.001). The formation and maturation of gametophytes were blocked in the 2-BP group, and most of them were arrested in the middle and late stages. Following 2-BP treatment, significantly down-regulated genes during the asexual stage of P. falciparum were significantly enriched in cell cycle regulation, mitosis, DNA damage/response and structural organization, and significantly down-regulated genes during the gametocyte stage were significantly enriched in biological processes of cell cycle (mitosis and G1/S transition), RNA regulation and metabolism (such as carbon catabolite repression 4-negative on TATA-less) and cell development and differentiation. Conclusion The palmitoylation modification plays an important role in the asexual reproduction and gametocyte generation and development of P. falciparum.

ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

ObjectiveTo understand the epidemiological distribution and gene evolutionary variation of influenza A (H3N2) viruses in Fengxian District, Shanghai, in the surveillance year of 2023, and to provide a reference basis for influenza prevention and control. MethodsThe prevalence of influenza virus in Fengxian District in the 2023 influenza surveillance year (April 2023‒March 2024) was analyzed. The hemagglutinin (HA) gene, neuraminidase (NA) gene, and amino acid sequences of 75 strains of H3N2 influenza viruses were compared with the vaccine reference strain for similarity matching and phylogenetic evolutionary analysis, in addition to an analysis of gene characterization and variation. ResultsIn Fengxian District, there was a mixed epidemic of H3N2 and H1N1 in the spring of 2023, with H3N2 being the predominant subtype in the second half of the year, and Victoria B becoming the predominant subtype in the spring of 2024. A total of 75 influenza strains of H3N2 with HA and NA genes were distributed in the 3C.2a1b.2a.2a.2a.3a.1 and B.4 branches, with overall similarity to the reference strain of the 2024 vaccine higher than that of the reference strain of the 2022 and 2023 vaccine. Compared with the 2023 vaccine reference strain, three antigenic sites and one receptor binding site were changed in HA, with three glycosylation sites reduced and two glycosylation sites added; where as in NA seven antigenic sites and the 222nd resistance site changed with two glycosylation sites reduced. ConclusionThe risk of antigenic variation and drug resistance of H3N2 in this region is high, and it is necessary to strengthen the publicity and education on the 2024 influenza vaccine and long-term monitoring of influenza virus prevalence and variation levels.

ObjectiveTo explore the central neuroregulation mechanism of heat-sensitive moxibustion for knee osteoarthritis on pain relief. MethodsThirty patients who did not have experience of Deqi （得气） during heat-sensitive moxibustion treatment were assigned to the "non-Deqi group"， while another 30 patients who had experience of Deqi were assigned to the "Deqi group". Both groups received moxibustion at the left Heding （EX-LE2） acupoint. In the Deqi group， after the patients experienced sensation of Deqi at the acupoint， moxibustion was applied at approximately 3 cm from the skin for 10 minutes； in the non-Deqi group， moxibustion was also applied at approximately 3 cm from the skin for 10 minutes. Both groups received treatment once daily for 10 consecutive days. Knee joint pain was assessed before and after treatment using the visual analog scale （VAS）. Resting-state functional magnetic resonance imaging （rs-fMRI） scans were performed on all participants before the first treatment session and after the final session on the 10th day. The fractional amplitude of low-frequency fluctuations （fALFF） maps before and after treatment were processed using the SPM12 module by MATLAB. ResultsAfter treatment， VAS scores in both groups were significantly lower than before treatment （P＜0.05 or P＜0.01）， with the Deqi group showing significantly lower VAS scores than the non-Deqi group （P＜0.01）. Compared to before treatment， the Deqi group exhibited significant activation in the prefrontal cortex （t = 6.28）， white matter （t = 6.36）， and left temporal lobe （t = 9.33）， while significant inhibition was observed in the occipital lobe （t = -9.86） and right cerebrum （t = -4.54， P＜0.01）； in the non-Deqi group， significant changes after treatment were observed in the left occipital lobe （t = -6.42）， left medial frontal gyrus （t = -4.35）， left middle frontal gyrus （t = -4.74）， right superior frontal gyrus （t = -4.82）， right superior temporal gyrus （t = -6.61）， and right cerebellar posterior lobe （t = -8.64）， all of which were in inhibited states （P＜0.01）. Compared to the non-Deqi group， the Deqi group exhibited significant activation after treatment in the external nucleus （t = 5.77）， white matter （t = 3.58）， right cerebrum （t = 5.84）， left cerebellum （t = 5.35）， and left cerebrum （t = 4.32）， while significant inhibition was observed in the prefrontal cortex （t = -4.16）， occipital lobe （t = -4.87）， and precentral gyrus （t = -4.46， P＜0.01）. ConclusionsHeat-sensitive moxibustion provides better analgesic effects for knee osteoarthritis under state of Deqi. Its central neuroregulation mechanism may be related to the involvement of the frontal lobe， temporal lobe， occipital lobe， external nucleus， white matter， right cerebrum， left cerebellum， left cerebrum， and precentral gyrus in modulating pain signals.

Objective:To investigate the efficacy of combined pelvic magnetic therapy and pelvic floor electromyographic (EMG) biofeedback therapy in perimenopausal women with pelvic floor dysfunction (PFD), and its effects on bladder function and urodynamic status.Methods:A total of 137 perimenopausal women with PFD treated at Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine between February 2022 and May 2024 were enrolled. They were randomly divided into a control group ( n=68) and a study group ( n=69) by random number table method. Both groups received Kegel exercises. The control group additionally received pelvic floor EMG biofeedback therapy. The study group received combined pelvic magnetic therapy and pelvic floor EMG biofeedback therapy. The outcomes compared between groups were as follows: Bladder Function: First urge voiding volume (FVS), maximum urge voiding volume (MVS), post-void residual urine volume (PVR), prolapse of pelvic floor organs, urodynamics: Pressure of urethral maximum measurement (PUM), maximum urethral closure pressure (PMUC), bladder compliance (BC), pelvic floor muscle function: Pelvic floor muscle strength grade (PFMT), pelvic floor resting pressure (RP), vaginal dynamic pressure (VDPT). Normally distributed continuous data were presented as xˉ± s and compared by independent samples t-test. Categorical data were presented as case (%) and compared by χ2 test. Ranked data were compared by Kruskal-Wallis H test. A P-value<0.05 was considered statistically significant. Results:Baseline characteristics showed no significant differences between groups ( P>0.05). At post-treatment, the study group had a significantly higher clinical effective rate of 97.10% (67/69) compared to the control group, which was 88.24% (60/68) ( χ2=3.98, P=0.046). At post-treatment, the study group had significantly higher FVS [(238.29±10.22) mL vs. (229.37±10.54) mL, t=5.03, P<0.001] and MVS [(436.57±12.48) mL vs. (428.23±12.75) mL, t=3.87, P<0.001], and significantly lower PVR [(5.14±1.28) mL vs. (6.96±1.21) mL, t=8.55, P<0.001] compared to the control group. At post-treatment, urodynamic parameters were significantly higher in the study group: PUM [(10.08±0.97) kPa vs. (8.54±0.73) kPa, t=10.49, P<0.001], PMUC [(8.71±0.75) kPa vs. (7.68±0.64) kPa, t=8.64, P<0.001], and BC [(396.58±30.49) mL/kPa vs. (378.86±32.91) mL/kPa, t=3.27, P<0.001]. For pelvic organ prolapse (POP-Q), the distribution were as follows: Study Group: Grade 0: 16, Grade Ⅰ: 34, Grade Ⅱ: 18, Grade Ⅲ: 1, Grade Ⅳ: 0, control Group: Grade 0: 9, Grade Ⅰ: 31, Grade Ⅱ: 23, Grade Ⅲ:5, Grade Ⅳ: 0. The difference was statistically significant ( Z=2.08, P=0.037). At post-treatment, pelvic floor muscle function was significantly higher in the study group: PFMT [(4.21±0.29) vs. (3.84±0.23), t=8.27, P<0.001], RP [(9.59±1.26) cmH?O vs. (8.34±1.17) cmH?O, t=6.02, P<0.001], and VDPT [(82.74±3.36) cmH?O vs. (77.45±3.52) cmH?O, t=9.00, P<0.001]. Conclusion:Combined pelvic magnetic therapy and pelvic floor EMG biofeedback therapy demonstrates significant efficacy in treating PFD in perimenopausal women. It markedly improves bladder function and urodynamic status.

Breast cancer is the most common malignant disease in women,it seriously threatens women's physical and mental health.Traditional surgical resection is the treatment of first choice.With the innovation of surgical treatment concept and the continuous development of medical technology,the thermal ablation technology,as a kind of local precision treatment,has gradually attracted the attention and application in medical field.Among thermal ablation techniques,micro wave ablation(MW A)is an emerging thermal ablation technology used in the treatment of breast cancer.Compared with traditional surgery,MW A has the advantages of less trauma,quick recovery,less complications,satisfactory cosmetic effect,and maximum protection of patient's organ functions.Moreover,some studies have revealed that MWA can motivate anti-tumor immune response,therefore,it is expected that MW A combined with immunotherapy may become a new therapeutic regimen.This article aims to make a detailed review about the latest research progress in MWA for the treatment of breast cancer.

Objective To investigate the safety and effectiveness of endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion(AIS-LVO)over 24 h after onset.Methods The clinical data of AIS-LVO patients who received endovascular treatment in Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2022 were retrospectively analyzed,including baseline characteristics,imaging findings,treatment,degree of vascular recanalization(modified thrombolysis in cerebral infarction grade 2b and 3 for successful recanalization)and prognosis.Results A total of 57 patients were included,including 42 males and 15 females,aged from 30 to 84 years old.The most common risk factors were hypertension(39 cases,68.4%),followed by smoking history(24 cases,42.1%),diabetes mellitus(17 cases,29.8%),previous stroke history(16 cases,28.1%),and atrial fibrillation(9 cases,15.8%).Before treatment,the National Institutes of Health stroke scale score was 12.84±7.04,and the Alberta Stroke Program early computed tomography score was 9.00(7.00,10.00).Vascular occlusion sites included middle cerebral artery occlusion in 27(47.4%)cases,internal carotid artery occlusion in 24(42.1%)cases,and tandem lesions in 6(10.5%)cases.The time from onset to femoral artery puncture was 38.30(28.17,53.71)h,and the time from femoral artery puncture to vascular recanalization was 52.00(38.50,92.50)min.General anesthesia was the main anesthesia method,accounting for 64.9%(37/57).The etiological types of stroke were mainly large artery atherosclerosis(38 cases,66.7%),cardiogenic embolism(9 cases,15.8%),unknown causes(6 cases,10.5%),and other clear causes(4 cases,7.0%).Mechanical thrombectomy was the first choice in 41(71.9%)cases,balloon dilatation/stenting was used in 35(61.4%)cases,of which 15(26.3%)cases were the first choice.Finally,53(93.0%)cases were recanalized successfully.In terms of complications,1(1.8%)case had symptomatic intracranial hemorrhage.The 90-d prognosis rate was 59.6%(34/57),and 3(5.3%)cases died.Conclusion Endovascular treatment for AIS-LVO patients over 24 h after onset has high recanalization rate and good safety,but it still needs to be further verified by randomized controlled trials.

Objective:To investigate the effects of Zhuanggu Zhitong Capsules on JNK signaling molecules and their phosphorylated proteins in postmenopausal osteoporosis model female mice.Methods:The rats were divided into sham-operation group, blank group, model group, positive drug group, and Zhuanggu Zhitong Capsules group according to the random number table method, with 10 rats in each group. The model group, the positive drug group and the Zhuanggu Zhitong Capsules group were prepared by bilateral ovarian detomy to prepare a female mouse model of postmenopausal osteoporosis. The positive drug group was given 0.9 mg/kg of alendronate sodium, the Zhuanggu Zhitong Capsules group was given was Zhuanggu Zhitong Capsules 1.944 g/kg for gavage, and the blank group, sham-operation group, and model group were given the same volume of normal saline for gavage, once a day for a total of 13 weeks. Rat vaginal exfoliated cells were stained with Wright's staining; serum Omentin-1 and 25(OH)D 3 levels were determined by ELISA; renal tissue and femoral structure were observed by HE staining; JNK and p-JNK protein expressions were detected by immunohistochemical staining; JNK mRNA levels were detected by PCR. Results:Compared with the model group, the serum levels of 25(OH)D3 and Omentin-1 in the Zhuanggu Zhitong Capsules group and the positive drug group increased ( P<0.01), the mean gray values of JNK and p-JNK protein in bone and kidney tissues decreased ( P<0.01), and the mRNA levels of JNK in bone and kidney tissues decreased ( P<0.01). Conclusion:Zhuanggu Zhitong Capsules can effectively improve the bone microstructure of postmenopausal osteoporotic rats, and its mechanism may be related to the regulation of JNK signaling pathway.

Tumor immunotherapy has emerged as a highly esteemed and rapidly evolving field in recent years,marked by the development of numerous significant therapeutic approaches. Among these,immune checkpoint inhibitors stand out as a pivotal strategy,attracting considerable attention due to their substantial research progress. This article provides a comprehensive review of the current research advancements in ten key immune checkpoints related to anti-tumor therapy,including PD-1/PD-L1,CTLA-4,LAG-3,TIM-3,TIGIT,and VISTA. By conducting an in-depth analysis of their mechanisms of action,clinical applications,and future research directions,this review aims to offer valuable insights and guidance for optimizing strategies in tumor immunotherapy.

Objective:To analyze the clinical characteristics of immune checkpoint inhibitor (ICI)-induced type 1 diabetes (T1D).Methods:This was a retrospective case series study of clinical data from 24 patients with ICI-T1D admitted to People′s Hospital of Henan Provincial between January 2018 and December 2024. The data collected included demographic characteristics, ICI usage, clinical manifestations, laboratory test results, and clinical outcome. Patients were categorized into mild and severe groups based on disease severity. Clinical characteristics between the two groups were compared using the Mann-Whitney U test. Results:Of the 24 patients, 21 (87.5%) were male and 3 (12.5%) were female, with an average age of (62.0±10.6) years. Patients in the severe disease group were significantly older than those in the mild disease group [(68.0±9.5) years vs. (58.4±9.8) years, P<0.05]. Compared to patients with mild disease, those with severe disease had significantly higher rates of impaired consciousness (9/9 vs.2/15), shorter ICI treatment cycles [3 (2, 6) vs. 6 (5, 8)], shorter time from ICI initiation to diabetes diagnosis [68 (31, 168) d vs. 162 (135, 235) d], and shorter time from the onset of diabetes symptoms to medical consultation [4 (2, 5) d vs. 8 (4, 26) d] (all P<0.05). The severe disease group also showed significantly higher blood glucose levels [43.0 (39.1, 57.3) mmol/L vs. 24.6 (19.6, 29.6) mmol/L] and a lower glycated hemoglobin level [6.8% (6.3%, 7.6%) vs. 7.9% (7.6%, 8.6%)], along with a higher incidence of fulminant T1D (8/9 vs. 2/15, all P<0.05). All patients received insulin injection therapy. After discharge, fasting C-peptide levels in 3 patients with mild disease showed a transient increase to 0.26, 0.43, 0.49 nmol/L but declined again after six months. Conclusions:ICI-T1D is characterized by acute onset and rapid progression. Older patients are more likely to develop severe disease. All patients require insulin therapy.