Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.

Objective To propose a deep learning neural network approach for transforming megavoltage computed tomography(MVCT)images of cervical cancer into pseudo kilovoltage computed tomography(kVCT)images with high signal-to-noise ratio and contrast-to-noise ratio,thus providing three-dimensional anatomical images and localization information required for adaptive radiotherapy of cervical cancer,and guiding the accelerator to achieve precise treatment.Methods The MVCT and kVCT images of 54 patients treated with cervical cancer radiotherapy were collected,with 44 cases randomly selected as the training set,and the remaining 10 cases as the test set.A cyclic generative adversarial network with gating mechanism and multi-channel data input was used to synthesize pseudo-kVCT images from MVCT images.The network training results were evaluated with imaging quality evaluation parameters,such as mean absolute error(MAE),peak signal-to-noise ratio(PSNR),and structural similarity index(SSIM).Results The MAE,PSNR,and SSIM of MVCT imagesvspseudo-kVCT(5:5)images were(24.9±0.7)HUvs(17.8±0.3)HU,(29.8±0.2)dBvs(30.7±0.2)dB,and 0.841±0.007 vs 0.898±0.003,respectively.Conclusion The generated pseudo-kVCT images have advantages in noise reduction and contrast enhancement,and can reduce the need for additional MV-kVCT electron density calibration in dose calculations.The dose calculation ability of pseudo-kVCT is comparable to that of MVCT,providing a possibility for the application of pseudo-kVCT images in image-guided adaptive radiotherapy.

As research delves deeper into the mechanisms of tumor immune responses,studies reveal the importance of microbial com-munities within the tumor microenvironment in tumor progression and their interactions with the host immune system.Intratumoral micro-biota could influence the tumor microenvironment,thereby promoting or inhibiting tumor growth and development.Despite this import-ance,the specific role of intratumoral microbiota impacting cancer immunotherapeutic efficacy remains largely unexplored.A deeper under-standing of the characteristics and biological functions of tumor-specific microbiota heralds a potential revolutionary innovation in cancer treatment.In this review,we introduce the discovery and sources of intratumoral microbiota,also addressing its composition,and discuss tumor tissue characteristics.Moreover,we briefly review the history of cancer immunotherapy development with a particular focus on the research progress concerning the impact of intratumoral microbiota on cancer immunotherapy.Furthermore,we explore emerging strategies that combine targeting intratumoral microbiota with immunotherapy to enhance immune efficacy,inhibit tumor progression,and improve cure rates,anticipating that this approach could represent a new direction for enhancing treatment outcomes and prospects.

ObjectiveTo investigate the mechanism of anti-pulmonary fibrosis of cannabidiol by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. MethodSD rats were randomly divided into blank group， model group， prednisone group（3.15 mg·kg^-1） and cannabidiol low， medium and high dose groups（12， 36， 108 mg·kg^-1）， with 8 rats in each group. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin（5 mg·kg^-1）， which was administered continuously for 28 days after successful modeling. The pathological changes of rat lung tissue were observed， and enzyme-linked immunosorbent assay（ELISA） was used to detect the expression levels of matrix metalloproteinase-7（MMP-7）， type Ⅱ alveolar cell surface antigen（KL-6）， pulmonary surfactant-associated protein A（SP-A） and SP-D in serum. The expression levels of type Ⅰ collagen（Col-Ⅰ） and fibronectin（FN） in lung tissues were detected by immunohistochemistry， and the expression of mucin 5 subtype AC（MUC5AC） was detected by immunofluorescence. UPLC-Q-TOF-MS was used to search for potential biomarkers and related metabolic pathways of cannabidiol in treating pulmonary fibrosis. ResultCompared with the blank group， there were a large number of inflammatory cell infiltration and continuous fibrosis lesions in the lung tissue of rats in the model group. Compared with the model group， the inflammatory infiltration and blue collagen deposition in the lung tissue of rats in the prednisone and cannabidiol groups were reduced. Compared with the blank group， the expressions of MMP-7， KL-6， SP-A and SP-D in serum of the model group were significantly increased（P<0.01）， while the expressions of MMP-7， KL-6， SP-A and SP-D in the prednisone and cannabidiol high dose groups were significantly decreased by comparing with the model group（P<0.05， P<0.01）. Compared with the blank group， the expression levels of Col-Ⅰ and FN in the lung tissues of the model group were significantly increased， and the fluorescence intensity of MUC5AC was significantly increased（P<0.01）. Compared with the model group， the expression levels of Col-Ⅰ and FN in the lung tissues of the prednisone and cannabidiol high dose groups were significantly decreased（P<0.05， P<0.01）， and the expression of MUC5AC was significantly decreased（P<0.01）. Compared with the blank group， a total of 18 differential compounds were screened out in the model group， which could be used as potential biomarkers， and cannabidiol could call back 16 of them， mainly involving 4 metabolic pathways（linoleic acid metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， arachidonic acid metabolism， and niacin and niacinamide metabolism）. Compared with the blank group， the relative contents of potential biomarkers arachidonic acid and linoleic acid were significantly increased in the model group（P<0.05， P<0.01）， while the relative contents of 5，6-EET， L-tyrosine and niacinamide were significantly decreased（P<0.01）. Compared with the model group， cannabidiol could significantly reduce the relative contents of arachidonic acid and linoleic acid， and significantly increase the relative contents of 5，6-EET， L-tyrosine and niacinamide（P<0.01）. ConclusionCannabidiol has an intervention and remission effect on pulmonary fibrosis， and its mechanism may be related to linoleic acid metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， arachidonic acid metabolism， niacin and niacinamide metabolism.

OBJECTIVE To construct the integrated pharmaceutical care model of in-hospital pharmaceutical care+out-hospital pharmacy outpatient service for patients with lower extremity artery disease （LEAD）， so as to improve patients’ disease self- management ability， and the efficacy and safety of therapy. METHODS The in-hospital pharmaceutical care and out-hospital pharmacy outpatient service model was constructed for LEAD patients， including pharmaceutical evaluation， self-management ability education， and pharmacy follow-up， to perform long-term management of patients. Totally 65 LEAD patients admitted to the vascular surgery department of our hospital， receiving pharmacist management， from September， 2021 to December， 2022 were selected as the study objects， and pharmacists conducted in-hospital pharmaceutical care+continuous out-patient management. The efficacy indicators， safety indicators， and patients’s disease self-management ability indicators were compared before and after 3 months of pharmacist management. RESULTS After 3 months of pharmacists’ participation in the management of 65 patients， Fontaine stage decreased in 55 patients， there was the significant difference in Fontaine stage before and after management （P＜ 0.001）. The proportion of patients who completely followed the guidelines for medication increased from 63.1% to 96.9%； the incidence of small bleeding was reduced by 7.7% after pharmacists’ management. The scores of Morisky medication compliance and patients’ disease self-management ability were higher than 3 months ago （P＜0.001）. Patient proportion with “good” medical satisfaction increased by 18.4%. CONCLUSIONS The in-hospital pharmaceutical care and out-hospital pharmacy outpatient service model of LEAD patients can effectively improve patients’ disease self-management ability， and improve the efficacy and safety of therapy.

Objective:To investigate the types, incidences, and clinical characteristics of shock in polytrauma patients at different stages after polytrauma.Methods:A retrospective study was conducted on polytrauma patients admitted to multiple trauma centers from June 2020 to December 2021. The inclusion criteria were patients >18 years old and treated due to polytrauma. Exclusion criteria included an admission time of more than 48 h after trauma, a history of malignancy, or metabolic, consumptive, and immunological diseases. The early stage was defined as the period of ≤48 h after polytrauma, and the middle stage was defined as the period between 48 h and 14 days. The patient’s medical history, clinical manifestations, laboratory tests, imaging examination, injury severity score (ISS), and Glasgow coma scale (GCS) were collected. The types, incidences, and clinical characteristics of shock in different stages after polytrauma were analyzed, according to the diagnostic criteria of each type of shock. The differences between the groups were compared by Student’s t test, χ2 test or Mann-Whitney U test. Results:The incidence of the early and middle stage shock after polytrauma were 73.1% and 36.4%, respectively, with statistically significant difference between stages ( P<0.01). There were significant differences in the incidence of hypovolemic shock (83.6% vs. 28.4%), distributed shock (13.7% vs. 80.9%) and cardiogenic shock (3.5% vs. 6.6%) between stages (all P<0.05). The incidence of obstructive shock (8.4% vs. 9.7%, P>0.05) was similar between stages. The incidence of undifferentiated shock was 1.6% and 1.2%, respectively. There were 9.5% patients with multifactorial shock in the early stage and 14.4% in the middle stage. Totally 7 combinations of multifactorial shock were found in different stages after polytrauma. In the early stage, the combination of HS and DS accounted the highest ratio (42.3%) and followed by HS and OS for 28.8%. In the middle stage, the combination of HS and DS was the most common (48.6%) and followed by DS and OS (24.3%). Conclusions:The incidence of shock in polytrauma patients is high. Different types of shock can occur simultaneously or sequentially. Therefore a comprehensive resuscitation strategy is significant to improve the success rate of treatment.

The massive loss of oligodendrocytes caused by various pathological factors is a basic feature of many demyelinating diseases of the central nervous system (CNS). Based on a variety of studies, it is now well established that impairment of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is a vital event in the failed treatment of demyelinating diseases. Recent evidence suggests that Foxg1 is essential for the proliferation of certain precursors and inhibits premature neurogenesis during brain development. To date, very little attention has been paid to the role of Foxg1 in the proliferation and differentiation of OPCs in demyelinating diseases of the CNS. Here, for the first time, we examined the effects of Foxg1 on demyelination and remyelination in the brain using a cuprizone (CPZ)-induced mouse model. In this work, 7-week-old Foxg1 conditional knockout and wild-type (WT) mice were fed a diet containing 0.2% CPZ w/w for 5 weeks, after which CPZ was withdrawn to enable remyelination. Our results demonstrated that, compared with WT mice, Foxg1-knockout mice exhibited not only alleviated demyelination but also accelerated remyelination of the demyelinated corpus callosum. Furthermore, we found that Foxg1 knockout decreased the proliferation of OPCs and accelerated their differentiation into mature oligodendrocytes both in vivo and in vitro. Wnt signaling plays a critical role in development and in a variety of diseases. GSK-3β, a key regulatory kinase in the Wnt pathway, regulates the ability of β-catenin to enter nuclei, where it activates the expression of Wnt target genes. We then used SB216763, a selective inhibitor of GSK-3β activity, to further demonstrate the regulatory mechanism by which Foxg1 affects OPCs in vitro. The results showed that SB216763 clearly inhibited the expression of GSK-3β, which abolished the effect of the proliferation and differentiation of OPCs caused by the knockdown of Foxg1. These results suggest that Foxg1 is involved in the proliferation and differentiation of OPCs through the Wnt signaling pathway. The present experimental results are some of the first to suggest that Foxg1 is a new therapeutic target for the treatment of demyelinating diseases of the CNS.

Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.

Objective: To explore the effects of combined transplantation of the rat Schwann cells and fibroblasts (Fbs) on the nerve regeneration of denervated perforator flaps in rats and the mechanism. Methods: (1) Fbs were isolated from the trunk of 2 Sprague-Dawley (SD) rats embryos of 14-16 days′ pregnancy and cultured, and the morphology of the cells was observed. The third passage of cells were used for subsequent experiments. The protein expressions of fibronectin and Ephrin-B2 were observed by immunohistochemical method. The mRNA expression of Ephrin-B2 was detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction (n=3). (2) Schwann cells were isolated from the bilateral sciatic nerves and brachial plexus nerves of 45 SD rats born for 1-3 days and cultured, and the morphology of the cells was observed. The third passage of cells were used for subsequent experiments. The rate of S100 positive cells was detected by immunofluorescence method and flow cytometer, with sample numbers of 9 and 3 respectively. (3) In Dulbecco′s modified Eagle medium (DMEM) high glucose medium, 1 mL Fbs and 1 mL Schwann cells both in the concentration of 1×10⁵ cells/mL were co-cultured as Schwann cells+ Fbs co-culture group, and 2 mL Schwann cells in the concentration of 1×10⁵ cells/mL were cultured alone as Schwann cells alone culture group, with 5 wells in each group. The clusters of Schwann cells in the two groups were observed and counted under inverted phase contrast microscope at post culture hour (PCH) 6 and 24 respectively. The clusters of Schwann cells in Schwann cells+ Fbs co-culture group were observed by immunofluorescence method at PCH 24 too. The protein expressions of EphB2, Sox2, and N-cadherin in Schwann cells of two groups at PCH 24 were detected by Western blotting (n=20). (4) Totally 100 8-week-old male SD rats were selected, and an in situ replanted peritoneal denervated perforator flap was made in each rat. According to the random number table, the rats were divided into simple flap group, Fbs alone transplantation group, Schwann cells alone transplantation group, Schwann cells+ Fbs co-transplantation group, with 25 rats in each group. Flaps of rats in Fbs alone transplantation group and Schwann cells alone transplantation group were injected with 0.4 mL Fb and 0.4 mL Schwann cells respectively (2×10⁶ cells each). Flaps of rats in Schwann cells+ Fbs co-transplantation group were injected with 0.4 mL Fbs and Schwann cells mixed cells (totally 2×10⁶ cells, cell number ratio: 1∶1), and flaps of rats of simple flap group were injected with the same volume of DMEM high glucose medium. On post injection day (PID) 2, 5, 7, 9, and 14, 5 rats in each group were selected respectively according to the random number table. The flap tissue was collected, and the number, diameter, and arrangement of regenerated nerves were observed by immunofluorescence method. Data were processed with completely random designed t test, analysis of variance for repeated measurement, t test, and Bonferroni correction. Results: (1) The third passage of cells isolated and cultured from the rat embryo trunks were uniform in size and shape, long spindle-shaped, with a large proportion of nuclei. Strong positive expressions of fibronectin and Ephrin-B2 protein in cells were observed, and the mRNA expression of Ephrin-B2 was 0.004 1±0.000 8. The cells were identified as Fbs. (2) After 5 days of culture, the primary cells isolated from the sciatic nerves and brachial plexus nerves of neonatal rats were elongated in cell bodies and grew in nest, fence, or vortex-like shape. The third passage of cells were detected by immunofluorescence method and flow cytometer, and the corresponding S100 positive cell rates were (95.9±1.0)% and (95.8±1.1)% respectively. The cells were identified as Schwann cells. (3) At PCH 6 and 24, the cluster numbers of Schwann cells in Schwann cells+ Fbs co-culture group were significantly higher than those of Schwann cells alone culture group (t=6.500, 10.614, P<0.01). At PCH 24, the Schwann cells in Schwann cells+ Fbs co-culture group aggregated into clusters, Fbs dispersed around the Schwann cell clusters, and the protein expressions of EphB2, N-cadherin, and Sox2 in Schwann cells were significantly higher than those in Schwann cells alone culture group (t=2.975, 19.717, 11.159, P<0.05 or P<0.01). (4) On PID 2, a small number of scattered, disordered, short, and thin nerve fibers were observed in the flap tissue of rats in the four groups. From PID 5 to 14, the number of nerve fibers in the flap tissue of rats of Schwann cells+ Fbs co-transplantation group increased gradually, and the nerve fibers were with long diameter and arranged orderly. The number of nerve fibers in the flap tissue of rats of Schwann cells alone transplantation group increased, but the nerve fibers were with short diameter and arranged disorderly, and the number was smaller than that of Schwann cells+ Fbs co-transplantation group. In simple flap group and Fbs alone transplantation group, the nerve fibers in the flap tissue of rats gradually degenerated with gradually decreased number or even disappeared. Conclusions The combined transplantation of Fbs and Schwann cells in rats can regulate Schwann cells migration and clustering by activating Ephrin/Eph-Sox2-N-cadherin signaling pathway, thus promoting the orderly nerve regeneration of denervated perforator flaps in rats.

Objective: To explore the effect of the perforator flap of the proper digital artery on the ulnar or radial side of the finger in the treatment of webbed scar contracture of the same finger in child. Methods: From January 2012 to January 2016, 26 children who were treated with dressing change after burn of finger and then had webbed scar contracture along with growth and development were hospitalized in our unit, involving a total of 50 fingers. There were 14 males and 12 females among the children aged from 2 to 14 years. After the scar was dissected and released, the wound area ranged from 1.6 cm×1.0 cm to 5.0 cm×2.6 cm. The perforator flap of the proper digital artery of the ulnar or radial side of the same finger was used to repair the wound. The flap area ranged from 1.8 cm×1.0 cm to 4.6 cm×1.8 cm. The donor sites were sutured directly. The residual wounds in donor and recipient sites were repaired by full-thickness skin graft collected from inguinal area/adjacent area or adjacent perforator flap. The postoperative development and function of the fingers were followed up and observed. The range of motion of the fingers was evaluated according to the Chinese Medical Association Hand Surgery Society′s upper limb functional evaluation trial standard, the Kantor Scar Cosmesis Assessment and Rating Scale was used to score the scar of finger, and the latest data were recorded. Results: The flaps and skin grafts survived successfully after operation. The patients were followed up for 6 to 24 months. The perforator flaps of the proper digital artery on the ulnar or radial side of the finger survived well at the latest follow-up, with good color and texture and a two-point discrimination distance of 9 to 12 mm. There was no contracture of the fingers, a little pigmentation in the skin graft area, no flexion deformity of the fingers, no lateral bending of the fingers to the flap-harvesting side, and no scar contracture at the webs of the fingers. Compared with that of healthy side, the development of finger was not obviously abnormal. The range of motion of the fingers was excellent in 38 fingers and good in 12 fingers, and the scar score of the fingers was 2-3 points in 31 fingers, 4-7 points in 15 fingers, and 8-10 points in 4 fingers. Conclusions The efficacy of perforator flap of the proper digital artery of the ulnar or radial side of finger in the treatment of the webbed scar contracture of the same finger in child is reliable, with high postoperative survival rate of the flap, better color and texture, and fewer complications, which can avoid the risk of re-contracture of the finger in a short period after operation, and does not affect the growth and development of the finger.