Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

BACKGROUND:The displacement change parameters of the bone structure of the first metatarsal bone at the two-dimensional level of hallux valgus deformity are of great significance for clinical diagnosis and treatment,while the quantitative analysis of the three-dimensional deformity index may have some influences on the postoperative efficacy. OBJECTIVE:To explore the quantitative change of the three-dimensional deformity index of the first metatarsal bone after routine osteotomy and orthosis for hallux valgus deformity and to provide reference for clinical work. METHODS:100 patients with hallux valgus deformity(foot)in Hengshui People's Hospital from October 2020 to April 2023 were selected and all of them underwent conventional osteotomy and orthosis.Foot function was assessed by the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale 6 months after surgery.Anterolateral X-rays of the foot in weight-bearing position and CT images in simulated weight-bearing position were taken before surgery and 6 months after surgery.The three-dimensional deformity indexes of the first metatarsal bone before and after surgery were quantitatively analyzed in patients with different ages,genders and therapeutic effects,including first-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle.The value of the difference of three-dimensional deformity indexes of the first metatarsal bone before and after operation in evaluating the curative effect was analyzed. RESULTS AND CONCLUSION:(1)Six months after operation,the American Orthopedic Foot and Ankle Society score was 75-98(88.25±4.14)points,among which 56 cases were excellent,28 cases were good,14 cases were average,and 2 cases were poor.The excellent and good rate was 84%(84/100).(2)Compared with the preoperative results,first-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle were significantly improved in patients of different ages and genders 6 months after surgery(P<0.05).First-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle were all lower in patients with good curative effect 6 months after surgery than those with poor curative effect,and the difference before and after surgery was greater than those with poor curative effect(P<0.05).(3)The area under the curve of the difference evaluation of the first metatarsal three-dimensional deformity index before and after surgery was above 0.7,and the area under the curve of the combined evaluation of all indexes was the largest(0.902),which was significantly greater than the first metatarsal rotation α angle and distal metatarsal articular angle(P<0.05).(4)The quantitative analysis of the three-dimensional deformity index of the first metatarsal in patients with hallux valgus deformity is related to the postoperative effect,which has important guiding significance for improving the accuracy and comprehensiveness of preoperative evaluation and improving the treatment plan.

In recent years， there have been both achievements and criticisms in using the methods of evidence-based medicine to evaluate the efficacy of traditional Chinese medicine （TCM）， which is mainly due to the differences between TCM and Western medicine. To facilitate the clinical evidence-based evaluation in TCM， this paper analyzes the challenges faced in TCM clinical evaluation， particularly in the diagnosis， clinical intervention， and efficacy assessment methods. Considering the current state of TCM clinical evaluation and our clinical research experience， we believe that establishing and refining the TCM disease-syndrome diagnostic system is a prerequisite for the practice of clinical evidence-based evaluation in TCM. Furthermore， this paper discusses the specific connotation， development， and challenges of the disease-syndrome diagnostic system， especially the choice of TCM disease name or modern medical disease name in this system. Then， the clinical application scenarios are expounded from ''TCM disease name + syndrome differentiation'' and ''Western medicine disease name + syndrome differentiation''. Moreover， this paper proposed solutions for practical issues such as the standardization of disease and syndrome diagnosis， selection of clinical evaluation methods， and application of evidence-based approaches in clinical evaluation. Establishing the criteria for the disease-syndrome diagnostic system is crucial for the determination of clinical intervention regimen， the selection of clinical research methods， and the establishment of evaluation indicators， which are essential for generating high-quality clinical evidence. To sum up， this paper reviews the development and current situation of the disease-syndrome diagnostic system and proposes an exploratory approach for the standardization and application of this system in clinical evidence-based evaluation. This approach aims to facilitate the integration of TCM with modern clinical practice， thereby achieving standardized evaluation of TCM efficacy and deepening the integration of TCM with evidence-based medicine.

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Humans ; Aortic Valve/surgery* ; Retrospective Studies ; Transcatheter Aortic Valve Replacement ; Sex Factors ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Aortic Valve Stenosis/surgery* ; Risk Factors ; Risk Assessment

This paper presented the clinical data of a 29-year-old female patient with acquired partial lipodystrophy (APL) admitted to the Second Hospital of Hebei Medical University in September 2020. The patient was admitted due to "facial fat loss". After comprehensive examination, APL was diagnosed. Autologous fat transplantation was conducted to improve the facial contour caused by fat volume loss.The result was satisfactory. Relevant literatures were also collectively reviewed for further discussion on APL.

This paper presented the clinical data of a 29-year-old female patient with acquired partial lipodystrophy (APL) admitted to the Second Hospital of Hebei Medical University in September 2020. The patient was admitted due to "facial fat loss". After comprehensive examination, APL was diagnosed. Autologous fat transplantation was conducted to improve the facial contour caused by fat volume loss.The result was satisfactory. Relevant literatures were also collectively reviewed for further discussion on APL.

Objective:To investigate the mechanism of levosimendan on acute kidney injury after cardiopulmonary resuscitation (CPR) in rats.Methods:Twenty-five healthy adult male SD rats were randomly divided into three groups: control group ( n=5), levosimendan group ( n=10) and experimental group ( n=10). A cardiac arrest-cardiopulmonary resuscitation model was established using smothering method in the experimental group and levosimendan group. The levosimendan group was treated with levosimandan during and after resuscitation, while the experimental group was given equivalent volume of saline solution during and after resuscitation, and the control group was only given equivalent volume of saline without performance of CPR. The rats in the three groups were sacrificed at 6 h after resuscitation. The serum and kidney tissue samples were collected. Serum biochemical indicators [serum creatinine (Scr), blood urea nitrogen (Bun), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] were measured. HE staining and Paller score were used to identify the degree of kidney damage. Apoptosis was estimated by TUNEL staining. Western blot was used to detect the expression levels of phosphorylation of extracellular regulated protein kinases (p-ERK). One-way analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between groups were performed using the least significant difference t-test. Results:Scr (85.02±1.31) μmol/L, Bun (7.36±0.13) mmol/L, Paller score (7.3±0.2), IL-1β (302.20±17.35) pg/mL, IL-6 (564.60±23.24) pg/mL and TNF-α (1346±83.73) pg/mL in the experimental group were significantly higher than those of the control group [(15.94±0.96) μmol/L, (2.95±0.18) mmol/L, (0.7±0.2), (7.27±0.44) pg/mL, (51.30±2.87) pg/mL, and (10.39±0.52) pg/mL] (all P<0.01). Compared with the experimental group, Scr (63.88±2.01) μmol/L, Bun (5.45±0.47) mmol/L, paller score (4.8±0.2), IL-1β (78.61±3.66) pg/mL, IL-6 (297.90±13.64) pg/mL and TNF-α (276.2±20.18) pg/mL were significantly decreased in the levosimendan group (all P<0.01). TUNEL staining showed that levosimendan could improve the apoptosis of renal cells ( P<0.01). The expression of p-ERK protein in the levosimendan group was significantly higher than that in the experimental group ( P<0.01). Conclusions:Lovosimendan could attenuate acute kidney injury following cardiac arrest and cardiopulmonary resuscitation via suppression apoptosis. The mechanism of levosimendan protective effect might be associated with activation of ERK signaling pathway.

Objective:To investigate the effect of Asarinin on the survival time of transplanted heart after allogeneic heterotopic heart transplantation and to further verify the anti-immune rejection effect of Asarinin in spleen and peripheral blood.Methods:Using 64 Wistar rats as donors, 64 SD rats as recipients to establish the allogeneic heterotopic heart transplantation model in rats.After successful transplantation, 64 rats were use simple randomization divided into control group, cyclosporine A(CsA) group, Asarinin group and half CsA + half Asarinin group with 16 rats in each group.CsA group was given 5 mg/kg by gavage; Asarinin group was given 25 mg/kg; half dose group was given CsA 2.5 mg/kg+ Asarinin 12.5 mg/kg and the control group was given the same volume of normal saline by gavage.After administration for 1 week, half of them were used to observe the survival time.The other half of the rats were fully anesthetized with chloral hydrate, spleen and peripheral blood were taken.Half of the spleen was taken to observe the slices under the microscope.The other half of spleen was used RT-PCR to detect the relative expression of IFN-γ and IL-4.The expression of co-stimulatory molecules CD80, CD86 and CD40 in peripheral blood were detected by flow cytometry.Results:Survival time of transplanted heart was control group (8.4±0.9), CsA group (30.5±8.3), Asarinin group (16.5±4.3) and half-dose group (26.1±5.2) days.Compared with control group, survival time of heart transplantation became prolonged in all groups and the difference was statistically significant ( P<0.05). HE staining of splenic tissue showed that, as compared with control group, the injury of each group was alleviated.The relative expression of IFN-γ in spleen was control group (1.055±0.083), CsA group (0.396±0.038), Asarinin group (0.833±0.094) and half-dose group (0.862±0.104). The last three groups were lower than control group and the difference was statistically significant ( P<0.05). The relative expression of IL-4 in spleen was control group (1.429±0.234), CsA group (3.808±0.729), Asarinin group (2.209±0.306) and half-dose group (2.323±0.321). The last three groups all spiked as compared with control group and the difference was statistically significant ( P<0.05). The expressions of CD80, CD86 and CD40 in peripheral blood were control group (98.21±0.54), (85.78±0.89) and (96.36±0.66), CsA group (89.26±0.36), (56.86±2.32) and (88.11±1.61), Asarinin group (94.19±0.47), (79.01±1.12) and (87.86±1.67) and half-dose group (94.87±0.74), (80.81±0.98) and (89.71±0.97) respectively.The last three groups were lower than control group and the difference was statistically significant ( P<0.05). Conclusions:Asarinin can prolong the survival time of transplanted heart after allogeneic heterotopic heart transplantation in rats, inhibit the immune injury of spleen after allogeneic heterotopic heart transplantation in rats, decrease IFN-γ in spleen, increase IL-4 in spleen and inhibit the expression of peripheral blood costimulatory molecules CD80, CD86 and CD40.

Due to good mechanical properties and biocompatibility, tissue engineering scaffolds have become the vital method for repairing and regenerating articular cartilage defects. With the continuous development of tissue engineering technology, many scaffolds preparation and formation methods have been developed and tested in the past decade, however, the preparation of ideal regenerative scaffolds remain controversial. As load-bearing tissue inside the body joints, the matrix structure and cell composition of articular cartilage are hierarchical, and there are several smooth natural gradients from the cartilage surface to the subchondral bone layer, including cell phenotype and number, specific growth factors, matrix composition, fiber arrangement, mechanical properties, nutrient and oxygen consumption. Therefore, in the design of regenerative scaffolds, it is necessary to achieve these gradients to regenerate articular cartilage in situ. In recent studies, many new biomimetic gradient scaffolds have been used to simulate the natural gradient of articular cartilage. These scaffolds show different mechanical, physicochemical or biological gradients in the structure, and have achieved good repair effects. The related articles on tissue engineering for the treatment of articular cartilage defects were retrieved by searching databases with key wordsarticular cartilage injury, cartilage repair and gradient scaffolds. In this work,the structural, biochemical, biomechanical and nutrient metabolism gradients of natural articular cartilage were studied and summarized firstly. Then, the latest design and construction of articular cartilage gradient scaffolds were classified. Besides that, the material composition (such as hydrogels, nanomaterials, etc.) and the preparation process (such as electrospinning, 3D printing, etc.) of grandient scaffolds were further enhanced. Finally, the prospect and challenge of biomimetic gradient scaffolds in cartilage engineering are discussed, which provides a theoretical basis for the successful application of gradient scaffolds in clinical transformation.