ObjectiveUlcerative colitis is a prevalent immunoinflammatory disease. Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis. The actin cytoskeleton contributes to regulating the proliferation, differentiation, and migration of Th17 and Treg cells. Wdr63, a gene containing the WD repeat domain, participates in the structure and functional modulation of actin cytoskeleton. Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition. This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis. MethodsWe constructed Wdr63^-/- mice, induced colitis in mice using dextran sulfate sodium salt, collected colon tissue for histopathological staining, collected mesenteric lymph nodes for flow cytometry analysis, and collected healthy mouse feces for microbial diversity detection. ResultsCompared with wild-type colitis mice, Wdr63^-/- colitis mice had a more pronounced shortening of colonic tissue, higher scores on disease activity index and histological damage index, Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes, a lower level of anti-inflammatory cytokine IL-10, and a higher level of pro-inflammatory cytokine IL-17A. In addition, WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis. It maintains the balance of Bacteroidota and Firmicutes, promoting the formation of beneficial intestinal bacteria linked to immune inflammation. ConclusionWdr63 deletion aggravates ulcerative colitis in mice, WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.

GBA1 gene mutation is an important genetic risk factor for Parkinson’s disease (PD). This paper reports a case of a 43-year-old male PD patient carrying a rare heterozygous Thr408Met mutation in the GBA1 gene identified through whole-exome sequencing, leading to a diagnosis of GBA1-associated PD. The patient’s motor symptoms were primarily characterized by bradykinesia and rigidity, without significant cognitive decline. Treatment with low-dose levodopa combined with a dopamine agonist resulted in significant symptomatic improvement.

ObjectiveTo explore the interaction among root fungi of Stellaria dichotoma var. lanceolata， soil factors， and main components of medicinal materials in lithosol habitats. MethodHigh-throughput sequencing technology was employed to determine the fungal community of the root system of S. dichotoma var. lanceolata at different levels （bulk soil， rhizosphere soil， rhizoplane soil， and root interior） and the soil properties of the root system （bulk and rhizosphere）， and the relationship among the fungal community， soil properties， and the main components of medicinal materials was analyzed. ResultThe total phosphorus， available phosphorus， alkaline nitrogen， dissolved organic carbon， and soil water content in the rhizosphere soil of S. dichotoma var. lanceolata were slightly higher than those in the rhizosphere， but the difference was not significant. Ascomycota is the dominant phylum of root fungi in S. dichotoma var. lanceolata. In the progressive level of bulk-rhizosphere-rhizoplane-root interior system， although the fungal diversity gradually decreased， the abundance of Hypocreales， a new phylum （unclassified_ k_ Fungi）， Helotiales， and Natipusilales gradually increased， among which Hypocreales is the most important fungal group in the root system of S. dichotoma var. lanceolata. The structural equation model （SEM） shows that the physicochemical factors of the root-soil play an important regulatory role in the fungal community and the main components of medicinal herbs， with soil total nitrogen， alkaline nitrogen， soil water content， and pH being the main regulatory factors. Soil nitrogen content is the key to promoting the main components of the medicinal herbs， and Penicillium fungi are the key fungal group to regulate the main components of the medicinal herbs. ConclusionIt highlights that the physicochemical properties of the soil of S. dichotoma var. lanceolata play a crucial role in the fungal community and the components of medicinal materials. Hypocreales fungi in the root of S. dichotoma var. lanceolata were an important group， and Penicillium fungi had a certain role in mediating the components of medicinal materials.

Lecanemab is a new drug used to treat early Alzheimer's disease (AD) with mild cognitive impairment or mild dementia. It is a human anti-Aβ fibril monoclonal IgG1 antibody, which is injected intravenously into the patient, through the blood-brain barrier into the brain, clearing amyloid plaque, thereby slowing the rate of cognitive decline in patients and delaying disease progression. This article reviews the pharmacological studies, clinical studies, safety and limitations of lecanemab, in order to help clinical understand the current research status and existing achievements of this drug.

Objective:To evaluate the robustness of fully automated adaptive planning for Ethos online adaptive radiotherapy (ART) based on the intelligent optimization engine (IOE).Methods:Clinical data of 11 stage ⅠB cervical cancer patients admitted to Peking Union Medical College Hospital between June 2021 and June 2022 were retrospectively analyzed. Original planning images and iterative cone-beam computed tomography (iCBCT) images of each radiotherapy treatment were acquired, and all patient data were imported into the Ethos simulator. IOE-based 9-field automatic plan generation was performed for 11 patients using Ethos, and the generated plans were sent to online adaptive radiotherapy simulation to obtain each online adaptive radiotherapy plan (273 fractions in total) and complete the simulated treatment. For comparison, manual plan design was performed based on the images and contoured structures used for online adaptive radiotherapy planning, and the manually plans created with evenly divided 9 fields. Dosimetric parameters, plan complexity parameters, and Mobius quality assurance (QA) pass rates were collected to compare and evaluate the robustness of the online adaptive radiotherapy plan in terms of organs at risk (OAR), target volume dosimetric parameters, and plan complexity by using paired t-test or rank sum test. Results:The online adaptive plan of cervical cancer had comparable planning target volume (PTV) coverage compared to the manual plan. For the clinical target volume (CTV) D 99%, online adaptive plan was significantly higher than the manual plan [(45.93±0.36) vs. (45.32±0.31) Gy, P<0.001]. For hot dose area, the maximum point dose (PTV D max) of adaptive plan was significantly higher than the manual plan [(49.89±1.25) vs. (48.48±0.77) Gy, P<0.001], but the PTV D 1% of adaptive plan was significantly lower than the manual plan [(47.22±0.29) vs. (47.59±0.48) Gy, P<0.001]. There was no statistical difference in the conformal index ( P=0.967). And there was significant difference in the homogeneity index, with same medians and less dispersion in adaptive plan ( P<0.001). For OAR dose, bladder D mean, rectal V 40 Gy, small intestine D mean of adaptive plan was slightly higher than that of the manual plan; the rectal D mean, small intestine D 2 cm3 of the adaptive plan was slightly lower than that of manual plan; dosimetric parameters of right and left femoral heads, spinal cord and bone marrow of the adaptive plan were better than those of manual plan. The adaptive plan had more monitor units (MU) than the manual plan, but the complexity of the adaptive plan was significantly lower than that of the manual plan (0.135±0.012 vs. 0.151±0.015, P<0.001). For Mobius γ pass rate (5%/3 mm), both adaptive and manual plans met clinical requirements. Conclusion:Ethos cervical cancer online adaptive plan, which is based on the IOE engine, demonstrates good robustness and ensures the quality of online adaptive plans generated for each treatment fraction.

Objective:To evaluate the automatic optimization performance and clinical feasibility of the intelligent optimization engine (IOE) in the Ethos online adaptive radiotherapy platform.Methods:Clinical data of 11 patients with postoperative cervical cancer treated with Halcyon accelerator were retrospectively analyzed. Manual planning was performed for all patients using the 4 full arc volumetric modulated arc therapy (VMAT) (Manual-4Arc) in Eclipse, with a prescription dose of 45 Gy/25F. Patient images and structures were imported into the Ethos simulator, and appropriate clinical goals were added based on clinical requirements. The target coverage was normalized to 95%. Automatic plan generation was conducted using IOE, resulting in 7, 9, and 12 field intensity modulated radiotherapy (IMRT) plans (IMRT-7F、IMRT-9F、IMRT-12F), as well as 2 and 3 arc VMAT plans (VMAT-2Arc、VMAT-3Arc). Dosimetric index comparisons were made between the Manual-4Arc plans and the 5 groups of IOE-generated plans through one-way analysis of variance. Based on the analysis results, Turky post hoc multiple comparisons were performed to evaluate the automatic optimization performance of IOE.Results:In terms of the high dose area, the IMRT-12F plans showed the lowest D 1% for the planning target volume (PTV), and there were significant differences compared to the Manual-4Arc plans ( P=0.004). Regarding target coverage, all groups produced clinical target volume (CTV) plans that met the clinical requirements. Although the Ethos online adaptive plans were normalized during planning, the PTV coverage was slightly insufficient. For organs at risk (OAR) close to the target, such as the bladder, there were significant differences in V 30 Gy, V 40 Gy, and D mean among the 6 groups of plans. The dose ranking for the bladder was generally as follows: IMRT-12F

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

Objective:To investigate the dosimetry effect of rotational errors of multi-channel cylinder vaginal applicator of intravaginal irradiation after surgery of endometrial cancer.Methods:A total of 18 patients who underwent surgery of endometrial cancer at Peking Union Medical College Hospital from June to December 2022 were selected.The plans of patients who adopted the treatment of multi-channel cylinder applicator of vagina were retrospectively analyzed,which maintained the same retained mode with clinical plan.The applicator was rotated clockwise by 22.5? and 45.0?,respectively,simulating the rotational errors that occurred in placing the applicator among clinical inter-fractions.And then,the changes of dosimetry of target area and organs at risk(OAR)under two kinds of rotation amplitudes were further analyzed.Results:When the applicator was rotated as 22.5?,the minimum doses to 90%volumes of CTV by 2.03%than that of clinical plan,which was significantly different(t=5.86,P<0.05),and the maximal doses to 2cc of OARs of bladder and rectum respectively increased 2.35%and 2.71%,and the differences of them were statistically significant(t=-3.49,-2.40,P<0.05),respectively.When the applicator was rotated as 45?,the D90 of the target area decreased by 5.75%than that of clinical plan,which was statistically significant(t=14.07,P<0.05).The D2cc values of the bladder and rectum increased respectively by 6.50%and 9.49%than that of clinical plan,which were statistically significant(t=-7.72,-6.9,P<0.05).The differences of the exposed doses of sigmoid colon and small intestine after the applicator was rotated by 22.5? and 45.0? between the plan and original plan were respectively less,which were not statistical significance.Conclusion:The multi-channel cylinder applicator can provide individualized dose distribution in intravaginal irradiation.However,attention should be paid to the placement of the applicator when patients undergo inter-fractional treatment,in order to avoid deviations in the angular alignment from the original plan.This can impact the dosages of the target area and OARs.

Tafamidis is a selective stabilizer for transthyretin （TTR）， used for the treatment of transthyretin amyloidosis with cardiomyopathy （ATTR-CM） and transthyretin amyloidosis with polyneuropathy （ATTR-PN）. This article provides a review of the basic information and clinical studies on the efficacy and safety of tafamidis. It is found that tafamidis slows down or prevents the progression of TTR amyloidosis by inhibiting the dissociation of TTR tetramers. Multiple clinical studies have shown that tafamidis has good efficacy and safety， significantly reducing all-cause mortality and cardiovascular-related hospitalization rates in patients with amyloidosis， and delaying disease progression. Although tafamidis treatment may have certain limitations， it is still a key drug for the treatment of TTR amyloidosis， and the first drug approved for the treatment of ATTR-CM.

Statistical analysis was conducted on the quantity of Chinese medicine material and sliced herbal medicine,the species types and medicinal parts of Chinese medicine material and sliced herbal medicine,and the quantity and composition of Chinese patent medicines and single-herb preparations in Chinese Pharmacopoeia of the 2020 edition.The statistical results are available on the web site(http://itcm.hzau.edu.cn/yd/zgyd.htm)for reference.The analysis results showed that:(1)Chinese Pharmacopoeia(Part I)contained a total of 616 kinds of Chinese medicine material and sliced herbal medicine and 47 kinds of plant oils and extracts.The 616 kinds of Chinese medicine material and sliced herbal medicine originated from plants,animals,minerals,microorganisms,artificial or synthetic raw materials,human-sourced products,and products having the origin of both animal and plants.Of the 47 kinds of plant oils and extracts,46 were made from plant sources,and the remaining one,i.e.Cornu Bubali concentrated powder,was made from the animal sources.(2)A total of 421(73.60%)from the 616 kinds of Chinese medicine material and sliced herbal medicine originated from the single species,96(16.78%)originated from 2 kinds of species,40(6.99%)originated from 3 kinds of species,11(1.92%)originated from 4 kinds of species,2(0.35%)originated from 5 kinds of species,and 2(0.35%)originated from 6 kinds of species.Of the 47 kinds of plant oils and extracts,34 originated from the single species,5 originated from 2 kinds of species and 5 originated from 3 kinds of species.(3)The Chinese Pharmacopoeia(Part I)contained a total of 1 605 Chinese patent medicines and single-herb preparations.Except that the composition of Yunnan Baiyao Powder and Yunnan Baiyao Capsules was not issued,the remaining 1 603 types of Chinese patent medicines and single-herb preparations involved a total of 14 329 kinds of medicinal materials.The Chinese medicines with the leading 20 frequency used in the Chinese patent medicines and single-herb preparations recorded in the Chinese Pharmacopoeia of 2020 edition were Glycyrrhizae Radix et Rhizoma,Angelicae Sinensis Radix,Poria,Chuanxiong Rhizoma,Scutellariae Radix,Paeoniae Radix Alba,Astragali Radix,Citri Reticulatae Pericarpium,Rehmanniae Radix,Atractylodis Macrocephalae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Borneolum Syntheticum,Platycodonis Radix,Rhei Radix et Rhizoma,Rehmanniae Radix Preparata,Aucklandiae Radix,Carthami Flos,Ophiopogonis Radix,Codonopsis Radix and Angelicae Dahuricae Radix.The results suggest that there were still problems existing in Chinese Pharmacopoeia of the 2020 edition,i.e.,some of the drugs of Chinese patent medicines were not listed in the Chinese medicine material and sliced herbal medicine,and some of the prepared drugs of Chinese patent medicines were not listed in the Chinese medicine material and sliced herbal medicine,either.The systemic analysis of the general information of Chinese medicinal materials as well as their correlation with Chinese patent medicines in Chinese Pharmacopoeia will provide a reference for further research on the production of Chinese medicine material and sliced herbal medicine and the complete list of drugs in Chinese patent medicines.