Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective:To explore the mechanisms of action of Huanglian Jiedu decoction combined with Xijiao Dihuang decoction (HLJDT-XJDH) in regulating fibroblasts in the treatment of psoriasis. Methods:A mouse model of psoriasis was established by topical application of imiquimod 5% cream on the shaved back; HLJDT-XJDH at different doses of 7.7 and 30.6 g/kg was administered via gavage for intervention, and methotrexate (2 mg/kg) served as a positive control; after 7 days, the severity of skin lesions was assessed using the psoriasis area and severity index (PASI), while histopathological changes of skin tissues were evaluated using hematoxylin-eosin (HE) staining and Baker scoring. For in vitro experiments, fibroblasts were divided into a control group, a model group, a low-dose (5% drug-containing serum) intervention group, and a high-dose (20% drug-containing serum) intervention group; cells in the control group were cultured with 20% normal rat serum for 24 hours; in the model group, cells cultured with 20% normal rat serum were stimulated with 5 ng/ml tumor necrosis factor (TNF) -α and 50 ng/ml interleukin (IL) -17A for 24 hours to mimic fibroblasts during the occurrence of psoriasis; cells in the low- and high-dose intervention groups received the same stimulation as the model group, and were cultured for 24 hours with 5% and 20% HLJDT-XJDH-containing serum, respectively, but not with the 20% normal rat serum. After the above treatment, these cells were co-cultured with keratinocytes (HaCaT cells) using a Transwell system. In addition, on the basis of the control group, fibroblasts were divided into the model group, 20% drug-containing serum intervention group, and 20% drug-containing serum intervention + OE-SFRP2 group; TNF-α and IL-17A were used to stimulate the cells to simulate the psoriatic state; the treatment in the 20% drug-containing serum intervention group was carried out as previously described; in the 20% drug-containing serum intervention + OE-SFRP2 group, cells were transfected with the vector for 48 hours to establish an overexpression model, followed by culture with 20% drug-containing serum for 24 hours, without co-culture with HaCaT cells.. Cell counting kit-8 (CCK-8) assay was performed to assess cell viability, flow cytometry to measure apoptosis rates, enzyme-linked immunosorbent assay (ELISA) to detect levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) as well as chemokine ligand (CXCL) 1 and CXCL12 in mouse serum or cell culture supernatant, qPCR to determine the mRNA expression of inflammatory cytokines, chemokines, cell cycle- and proliferation-related factors, as well as SFRP2 in mouse skin tissues or cells, and Western blot analysis to determine the protein expression of SFRP2, Wnt3a, and β-catenin in fibroblasts. One-way analysis of variance was employed for intergroup comparisons, and post-hoc analysis was conducted using Tukey's test. Results:In vivo mouse experiments showed that compared with the normal control group, the model group exhibited typical psoriatic characteristics in skin morphology, including significant inflammatory infiltration in skin tissues and marked epidermal thickening; compared with the normal control group, the serum levels of TNF-α (531.16 ± 28.27 pg/ml vs. 239.58 ± 10.39 pg/ml), IL-1β (111.40 ± 5.16 pg/ml vs. 80.35 ± 3.87 pg/ml), and IL-6 (109.17 ± 4.84 pg/ml vs. 71.73 ± 2.04 pg/ml) significantly increased in the model group, along with their mRNA expression levels in mouse skin tissues (all P < 0.001) ; compared with the model group, the treatment group showed alleviated psoriatic manifestations, and significant reductions in the levels of inflammatory factors TNF-α (low-dose, high-dose, and positive control groups: 420.80 ± 29.30 pg/ml, 322.33 ± 9.40 pg/ml, 322.97 ± 12.16 pg/ml, respectively), IL-1β (98.69 ± 4.49 pg/ml, 89.02 ± 1.56 pg/ml, 88.88 ± 2.08 pg/ml, respectively), and IL-6 (94.07 ± 3.76 pg/ml, 80.54 ± 3.30 pg/ml, 83.21 ± 3.18 pg/ml, respectively), as well as in their mRNA expression levels (all P < 0.001). In in vitro fibroblast experiments, compared with the control group, the model group exhibited a significant elevation in the supernatant levels of IL-1β (126.42 ± 3.56 pg/ml vs. 34.81 ± 0.44 pg/ml), IL-6 (459.44 ± 9.35 pg/ml vs. 115.51 ± 7.26 pg/ml), CXCL1 (2 434.88 ± 127.63 pg/ml vs. 762.85 ± 30.60 pg/ml) and CXCL12 (3 542.14 ± 35.86 pg/ml vs. 2 095.86 ± 45.12 pg/ml), the expression levels of their mRNAs (all P < 0.001), as well as the protein expression levels of SFRP2, Wnt3a, and β-catenin; after intervention with HLJDT-XJDH-containing serum, all the above indices significantly decreased (all P < 0.001). However, when 20% drug-containing serum intervention was administered simultaneously, the expression of inflammatory factors and chemokines in fibroblasts was significantly higher in the SFRP2 overexpression group than in the non-overexpression group (all P < 0.01). When fibroblasts were co-cultured with HaCaT cells, the model group showed significantly increased cell viability but a decreased apoptosis rate of HaCaT cells compared with the control group, while the low- and high-dose intervention groups showed significantly decreased cell viability but increased apoptosis rates of HaCaT cells compared with the model group (all P < 0.05) . Conclusion:HLJDT-XJDH may exert therapeutic effects in psoriasis by downregulating the SFRP2/Wnt/β-catenin signaling pathway, thereby inhibiting fibroblast activation and inflammatory process, which subsequently suppresses the proliferation of keratinocytes and the activation of inflammatory cells.

Objective:To explore the mechanisms of action of Huanglian Jiedu decoction combined with Xijiao Dihuang decoction (HLJDT-XJDH) in regulating fibroblasts in the treatment of psoriasis. Methods:A mouse model of psoriasis was established by topical application of imiquimod 5% cream on the shaved back; HLJDT-XJDH at different doses of 7.7 and 30.6 g/kg was administered via gavage for intervention, and methotrexate (2 mg/kg) served as a positive control; after 7 days, the severity of skin lesions was assessed using the psoriasis area and severity index (PASI), while histopathological changes of skin tissues were evaluated using hematoxylin-eosin (HE) staining and Baker scoring. For in vitro experiments, fibroblasts were divided into a control group, a model group, a low-dose (5% drug-containing serum) intervention group, and a high-dose (20% drug-containing serum) intervention group; cells in the control group were cultured with 20% normal rat serum for 24 hours; in the model group, cells cultured with 20% normal rat serum were stimulated with 5 ng/ml tumor necrosis factor (TNF) -α and 50 ng/ml interleukin (IL) -17A for 24 hours to mimic fibroblasts during the occurrence of psoriasis; cells in the low- and high-dose intervention groups received the same stimulation as the model group, and were cultured for 24 hours with 5% and 20% HLJDT-XJDH-containing serum, respectively, but not with the 20% normal rat serum. After the above treatment, these cells were co-cultured with keratinocytes (HaCaT cells) using a Transwell system. In addition, on the basis of the control group, fibroblasts were divided into the model group, 20% drug-containing serum intervention group, and 20% drug-containing serum intervention + OE-SFRP2 group; TNF-α and IL-17A were used to stimulate the cells to simulate the psoriatic state; the treatment in the 20% drug-containing serum intervention group was carried out as previously described; in the 20% drug-containing serum intervention + OE-SFRP2 group, cells were transfected with the vector for 48 hours to establish an overexpression model, followed by culture with 20% drug-containing serum for 24 hours, without co-culture with HaCaT cells.. Cell counting kit-8 (CCK-8) assay was performed to assess cell viability, flow cytometry to measure apoptosis rates, enzyme-linked immunosorbent assay (ELISA) to detect levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) as well as chemokine ligand (CXCL) 1 and CXCL12 in mouse serum or cell culture supernatant, qPCR to determine the mRNA expression of inflammatory cytokines, chemokines, cell cycle- and proliferation-related factors, as well as SFRP2 in mouse skin tissues or cells, and Western blot analysis to determine the protein expression of SFRP2, Wnt3a, and β-catenin in fibroblasts. One-way analysis of variance was employed for intergroup comparisons, and post-hoc analysis was conducted using Tukey's test. Results:In vivo mouse experiments showed that compared with the normal control group, the model group exhibited typical psoriatic characteristics in skin morphology, including significant inflammatory infiltration in skin tissues and marked epidermal thickening; compared with the normal control group, the serum levels of TNF-α (531.16 ± 28.27 pg/ml vs. 239.58 ± 10.39 pg/ml), IL-1β (111.40 ± 5.16 pg/ml vs. 80.35 ± 3.87 pg/ml), and IL-6 (109.17 ± 4.84 pg/ml vs. 71.73 ± 2.04 pg/ml) significantly increased in the model group, along with their mRNA expression levels in mouse skin tissues (all P < 0.001) ; compared with the model group, the treatment group showed alleviated psoriatic manifestations, and significant reductions in the levels of inflammatory factors TNF-α (low-dose, high-dose, and positive control groups: 420.80 ± 29.30 pg/ml, 322.33 ± 9.40 pg/ml, 322.97 ± 12.16 pg/ml, respectively), IL-1β (98.69 ± 4.49 pg/ml, 89.02 ± 1.56 pg/ml, 88.88 ± 2.08 pg/ml, respectively), and IL-6 (94.07 ± 3.76 pg/ml, 80.54 ± 3.30 pg/ml, 83.21 ± 3.18 pg/ml, respectively), as well as in their mRNA expression levels (all P < 0.001). In in vitro fibroblast experiments, compared with the control group, the model group exhibited a significant elevation in the supernatant levels of IL-1β (126.42 ± 3.56 pg/ml vs. 34.81 ± 0.44 pg/ml), IL-6 (459.44 ± 9.35 pg/ml vs. 115.51 ± 7.26 pg/ml), CXCL1 (2 434.88 ± 127.63 pg/ml vs. 762.85 ± 30.60 pg/ml) and CXCL12 (3 542.14 ± 35.86 pg/ml vs. 2 095.86 ± 45.12 pg/ml), the expression levels of their mRNAs (all P < 0.001), as well as the protein expression levels of SFRP2, Wnt3a, and β-catenin; after intervention with HLJDT-XJDH-containing serum, all the above indices significantly decreased (all P < 0.001). However, when 20% drug-containing serum intervention was administered simultaneously, the expression of inflammatory factors and chemokines in fibroblasts was significantly higher in the SFRP2 overexpression group than in the non-overexpression group (all P < 0.01). When fibroblasts were co-cultured with HaCaT cells, the model group showed significantly increased cell viability but a decreased apoptosis rate of HaCaT cells compared with the control group, while the low- and high-dose intervention groups showed significantly decreased cell viability but increased apoptosis rates of HaCaT cells compared with the model group (all P < 0.05) . Conclusion:HLJDT-XJDH may exert therapeutic effects in psoriasis by downregulating the SFRP2/Wnt/β-catenin signaling pathway, thereby inhibiting fibroblast activation and inflammatory process, which subsequently suppresses the proliferation of keratinocytes and the activation of inflammatory cells.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective To evaluate the effect of transcutaneous neuromuscular electrical stimulation on prevention of intensive care unit-acquired weakness (ICU-AW) in chronic obstructive pulmonary disease (COPD) patients with mechanical ventilation. Methods A prospective randomized controlled study was conducted. Sixty COPD patients aged 18-85 years old who were accepted mechanical ventilation therapy admitted to general intensive care unit (ICU) of the First Affiliated Hospital of Hunan University of Medicine from October 2017 to October 2018 were enrolled. Patients were divided into control group (n = 30) and intervention group (n = 30) by random number table method. All patients were accepted routine treatment, and on this basis, the intervention group was applied transcutaneous neuromuscular electrical stimulation on the extremities (twice a day, 30 minutes each time) after 24 hours of admission until ICU discharge. The Medical Research Council muscle strength score (MRC-Score), grip strength, incidence of ICU-AW on the 7th day after admission and on the day of ICU discharge; modified Barthel index score on the day of ICU discharge; and duration of mechanical ventilation, the length of ICU stay, and the length of hospital stay were compared between the two groups. Results Twenty-nine and 27 patients in the control group and the intervention group respectively finally completed the study in dividually. There was no significant difference in gender, age, Barthel index score before 2 weeks of ICU admission, body mass index or acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) in ICU between the two groups. There was no significant difference in the MRC-Score, grip strength or incidence of ICU-AW on the 7th day after ICU admission between the two groups. Compared to the control group, the MRC-Score, grip strength and Barthel index score in the intervention group were significantly increased [MRC-Score: 55.97±8.43 vs. 46.32±7.36, grip strength (kg): 33.46±11.62 vs. 27.42±9.64, Barthel index score:46.04±5.46 vs. 42.13±3.32, all P < 0.05], the incidence rate of ICU-AW was significantly decreased [7.4% (2/27) vs. 31.0% (9/29), P < 0.05], and duration of mechanical ventilation, the length of ICU stay, the length of hospital stay were significantly shortened [duration of mechanical ventilation (days): 5.12±2.01 vs. 7.24±4.35, the length of ICU stay (days): 8.34±2.36 vs. 10.45±2.62, the length of hospital stay (days): 13.21±2.21 vs. 15.38±3.67, all P < 0.05]. Conclusion Transcutaneous neuromuscular electrical stimulation can effectively improve the muscle strength of COPD patients with mechanical ventilation and reduce the incidence of ICU-AW.

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects