Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

The essence of asymptomatic syndrome differenciation is that the disease is in a special stage or state. To perform traditional Chinese medicine （TCM） diagnosis when there was no symptoms for differentiation is a key scientific issue in current TCM diagnosis and treatment. The reasons include limitations in doctor-patient behaviors and relationships， as well as limitations in cognitive thinking. To address such situations， the following strategies can be adopted from a thinking perspective，i.e. grasping the occurrence and development of diseases based on a holistic concept， using dialectical thinking to summarize the laws of diseases， integrating clinical practice with experiential thinking， and introducing new thinking modes through interdisciplinary collaboration. These strategies help TCM practitioners make accurate diagnoses in the absence of obvious symptoms， thereby providing better medical services for patients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the clinical effects of anatomical reconstruction of the deltoid ligament and medial migration calcaneal osteotomy in the treatment of chronic ankle instability after trauma.Methods:A retrospective study was conducted to analyze of the clinical data of 16 patients with chronic post-traumatic instability of the medial malleolus who had been treated at The Eighth Department of Orthopedics, Foshan Hospital of Traditional Chinese Medicine from December 2015 to February 2017. There were 14 males and 2 females with an age of (28.1±4.2) years. Seven left sides and 9 right sides were affected; the time from injury to operation was (8.9±2.4) months. Before operation, X-rays (anteroposterior, lateral and Saltzman views) and MRI of weight-bearing ankle were taken. All patients were treated by anatomical reconstruction of the deltoid ligament using the autologous semitendinosus and medial migration osteotomy of the calcaneus. The time for injury healing and occurrence of complications were recorded. The talus tilt angle, Meary angle, hindfoot valgus angle, visual analogue scale (VAS), and the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot function score were compared between the preoperation and the last follow-up. The Sefton evaluation for efficacy in ankle ligament reconstruction was used to assess stability of the ankle joint.Results:Of this cohort, 14 patients were followed up for (16.4±4.9) months after operation and 2 patients lost to follow-up. The 14 patients all returned to normal physical activities 3 months after operation. All incisions healed at the first stage with no infection. One patient experienced pain at the site for harvest of the semitendinosus but the symptoms were relieved after rehabilitation treatment like massage and physical therapy. At the last follow-up, the talus tilt angle [1.0 (0.0, 2.0)°], Meary angle (1.4°±4.2°), hindfoot valgus angle (3.2°±2.4°), VAS score [0.5 (0.0, 1.0) points], and AOFAS ankle-hindfoot score [(89.2±6.1) points] were all significantly improved compared with the preoperative values [8.3°±1.8°, 0.8°±3.8°, 9.9°±3.4°, (5.7±2.5) points, and (49.6±9.8) points] (all P<0.05). According to the Sefton evaluation, the stability of the ankle joint was excellent in 9 cases, good in 4 cases, and fair in 1 case. Conclusion:In the treatment of chronic ankle instability after trauma, anatomical reconstruction of the deltoid ligament and medial migration calcaneal osteotomy is safe and effective, resulting in limited complications.

Objective:To investigate the predictive value of preoperative lymphocyte-to-monocyte ratio (LMR) combined with platelet-to-lymphocyte ratio (PLR) (LMR-PLR) scoring model for prognosis of pancreatic ductal adenocarcinoma (PDAC) after radical resection.Methods:The retrospective cohort study was conducted. The clinicopathological data of 116 patients with PDAC who were admitted to the Second Hospital of Lanzhou University from January 2015 to December 2019 were collected. There were 73 males and 43 females, aged 61.5(range, 29.0-75.0)years. All patients underwent radical resection for PDAC. Observation indicators: (1) optimal cut-off value of LMR and PLR; (2) clinicopathological features of patients with different scores of preoperative LMR-PLR scoring model; (3) follow-up and survival; (4) influencing factors for prognosis of PDAC patients; (5) construction and verification of nomogram prediction model. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Graphpad prism 8 was used to draw survival curve, the Kaplan-Meier method was used to calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional hazard regression model was used for univariate and multivariate analyses. The X-tile software was used to determine the optimal cut-off values of LMR and PLR. The nomogram prediction model was conducted based on the results of multivariate analysis, and the receiver operating characteristic (ROC) curve was drawn. The area under curve (AUC) was used to evaluate the discrimination of nomogram prediction model. The calibration curve was used to evaluate the consistency of nomogram prediction model and the decision curve was used to evaluate the clinical benefits. Results:(1) Optimal cut-off value of LMR and PLR. The optimal cut-off values of LMR and PLR were 1.9 and 156.3. (2) Clinicopathological features of patients with different scores of preoperative LMR-PLR scoring model. Cases with LMR-PLR scoring as 0, 1, 2 were 11, 42, 63. Cases with CA125 <12.4 U/mL, cases postoperative with vascular invasion, cases with postoperative chemotherapy in patients with 0, 1, 2 of LMR-PLR scoring were 1, 8, 24, 9, 27, 27, 3, 26, 43, showing significant differences among them ( χ2=6.73, 8.37, 6.68, P<0.05). (3) Follow-up and survival. All 116 patients were followed up for 39(range, 2-86)months. The 1-, 2-, 3-year survival rate of 116 PDAC patients was 50.9%, 37.9%, 19.3%, respectively, with a survival time of 13(range, 1-85)months. The survival time of patients with LMR-PLR scoring as 0, 1, 2 was 3(range, 1-9)months, 7(range, 2-56)months, 26(range, 2-85)months, respectively, showing a significant difference among them ( χ2=48.78, P<0.05). (4) Influencing factors for prognosis of PDAC patients. Results of multivariate analysis showed that carcinoembryonic antigen (CEA), CA19-9, LMR-PLR score, tumor diameter were independent factors affecting prognosis of patients ( hazard ratio=1.61, 1.88, 0.27, 1.87, 95% confidence interval as 1.02-2.54, 1.18-3.00, 0.19-0.39, 1.13-3.09, P<0.05). (5) Construction and verification of nomogram prediction model. The nomogram prediction model was constructed based on CEA, CA19-9, LMR-PLR score and tumor diameter. The AUC of ROC curve in predicting 1-, 2-, 3-year survival rate of patients was 0.86 (95% confidence interval as 0.79-0.93, P<0.05), 0.86 (95% confidence interval as 0.79-0.92, P<0.05), 0.87 (95% confidence interval as 0.78-0.95, P<0.05), respectively. Results of calibration curve showed that the predicted survival rate of nomogram prediction model was consistent with the actual survival rate, with the consistency index as 0.74. Results of decision curve showed that the predictive performance of nomogram prediction model was superior to that of a single factor at a risk threshold of 0.12-0.85. Conclusions:CEA, CA19-9, LMR-PLR score, tumor diameter are independent factors affecting prognosis of patients undergoing radical resection for PDAC, and the nomogram prediction model can predict postoperative survival rate. The predicted survival rate of nomogram prediction model is consistent with the actual survival rate, and the predictive performance of nomogram prediction model is superior to that of a single factor at a risk threshold of 0.12-0.85.

Objective To investigate the predictive value of preoperative fibrinogen/albumin ratio (FAR) and systemic immune inflammation index (SII) on the postoperative prognosis of patients with pancreatic ductal adenocarcinoma. Methods An ROC curve was used in determining the best cutoff values of FAR and SII and then grouped. The Cox proportional hazards model was used in analyzing the prognostic factors of radical pancreatic cancer surgery, and then a Nomogram prognostic model was established. C-index, AUC, and calibration curve were used in evaluating the discrimination and calibration ability of the Nomogram. DCA curves were used in assessing the clinical validity of the Nomograms. Results The optimal cutoff values for preoperative FAR and SII were 0.095 and 532.945, respectively. FAR≥ 0.095, SII≥ 532.945, CA199≥ 450.9 U/ml, maximum tumor diameter≥ 4 cm, and the absence of postoperative chemotherapy were independent risk factors for the poor prognosis of pancreatic cancer (P<0.05). The discrimination ability, calibration ability, and clinical effectiveness of Nomogram prognostic model were better than those of the TNM staging system. Conclusion The constructed Nomogram prognostic model has higher accuracy and level of discrimination and more clinical benefits than the TNM staging prognostic model.

To construct a prokaryotic promoter report system with wide applicability, a series of pFGH reporter vectors based on lacZ gene and pUC replicon were constructed from plasmid pFLX107 through the replacement of multiple cloning sites and sequence modifications. The plasmid with the lowest background activity was selected as the final report system with the lacZ gene deletion strain MC4100 as the host bacterium, following by testing with inducible promoter araBAD and the constitutive promoter rpsM. The background activity of pFGH06 was significantly lower than that of other plasmids of the same series, and even lower than that of reference plasmid pRCL at 28 °C (P<0.01). Further evaluation tests show that the plasmid pFGH06 could be used to clone and determine the activity of inducible promoter or constitutive promoter, and the complete recognition of the target promoter could be achieved through blue-white selection in the simulation test of promoter screening. Compared with the reported prokaryotic promoter report systems, pFGH06 has the advantages of smaller size, more multiple clone sites, adjustable background activity, high efficiency of promoter screening and recognition, thus with a wide application prospect.
Cloning, Molecular ; Escherichia coli/genetics* ; Genes, Reporter/genetics* ; Genetic Vectors/genetics* ; Lac Operon/genetics* ; Plasmids/genetics* ; beta-Galactosidase/genetics*

Objective:To evaluate three-stage induced membrane technique combined with anterior and posterior double-plate fixation in the treatment of a total talus defect after infection.Methods:Included in this study were 11 patients with talus infection who had been treated at Department of Orthopaedics, Foshan Hospital of Traditional Chinese Medicine from January 2014 to December 2018. They were 8 males and 3 females, aged from 23 to 63 years (mean, 37.0 years). The infection followed re-implantation after open dislocation of total talus in 4 cases, internal fixation for open talus fracture of Gustilo type Ⅲa in 3 cases and surgery of open ankle fracture of Gustilo type Ⅲc in 2 cases, and was complicated with ankle intraarticular tuberculosis in 2 cases. The three-stage operations consisted of debridement, total talus resection, implantation of antibiotic bone cement and vacuum sealing drainage at the first stage, change of bone cement, re-debridement, wound closure or flap covering at the second stage 7 to 10 days later, and reconstruction after infection control using anterior and posterior double-plate fixation and induced membrane technique at the third stage 6 to 12 weeks later. Assessment of lower limb shortening was performed by comparing the full length of the leg between the normal and affected sides; the functions were assessed by comparing the ankle-hindfoot scores of American Orthopedic Foot and Ankle Society (AOFAS) and visual analogue scale (VAS) between preoperation and the final follow-up.Results:The 11 patients were followed up for an average of 24.3 months (from 12.2 to 37.5 months). Superficial skin necrosis was observed in 2 patients and injury to superficial peroneal nerve in one. Absolute calcification of the autograft area was observed in all patients, leading to ankle fusion. The final follow-ups observed no significant difference in the full length of the leg between the normal and affected sides [(380.4±35.5) mm versus (376.3±32.8) mm] ( P>0.05) , a significant increase in the ankle-hindfoot AOFAS scores from preoperative 28.0±3.4 to 72.8±5.4, and a significant decrease in VAS scores from preoperative 5(5,6) to 0(0,1) (all P<0.05). Slight varus developed in 2 patients and slight ankle stiffness in 3; recurrence of infection or breakage of implants was found in none of the patients. Conclusion:Three-stage induced membrane technique combined with anterior and posterior double-plate fixation can effectively control infection of the talus, maintain the length and reconstruct the function of the lower limb after a total talus defect.

Objective:To study the efficacy of minimally PCWO combined with Akin osteotomy on severe hallux valgus.Methods:This retrospective study was conducted on 45 patients (50 feet) with severe hallux valgus treated by minimally PCWO combined with Akin osteotomy in Eight Department of Bone, Foshan Hospital of traditional Chinese Medicine from August 2016 to August 2018. HVA, IMA, DMAA, DASA, IPA were measured by X-ray examination preoperatively and after operative 3, 6, 12 months and at the final follow-up. The efficacy was evaluated in accordance with the American Orthopaedic Foot and Ankle Association (AOFAS) Ankle Hindfoot Scale and the Olerud-Molander Ankle (OMA) Score. The absolute and relative lengths of the first metatarsus were measured by X-ray examination preoperatively and at the last follow-up, with calculating the differences.Result:All patients were followed up within 18.20±2.04 months. There was no recurrence during follow-up period. HVA was 42.83°±4.63°, 12.83°±1.53°, 13.49°±1.33°, 14.08°±1.49° and 14.12°±1.35° at the preoperative, postoperative 3 months, 6 months, 12 months and the last follow-up, respectively, and the difference between pre-operation and post-operation was statistically significant ( P<0.05). IMA was 18.29°±0.94°, 7.84°±1.22°, 8.31°±1.03°, 9.01°±1.08° and 9.09°±1.11° at the preoperative, postoperative 3 months, 6 months, 12 months and the last follow-up, respectively, and the difference between pre-operation and post-operation was statistically significant ( P<0.05). AOFAS scores were 50.64±7.94, 88.80±2.68, 90.10±3.51, 91.20±3.89 and 91.37±3.71 points at the preoperative, postoperative 3 months, 6 months, 12 months and the last follow-up, respectively, and the difference between pre-operation and post-operation was statistically significant ( P<0.05). The OMA scores were 61.00±7.00, 90.90±5.02, 91.60±4.57, 93.20±3.61 and 93.48±4.91 at preoperative, postoperative 3 months, 6 months, 12 months and the last follow-up, respectively, and the difference between pre-operation and post-operation was statistically significant ( P<0.05). The absolute shortening of the first metatarsal was 3.03 mm and relative shortening was 0.72 mm. Conclusion:For severe hallux valgus, minimally PCWO combined with Akin osteotomy can effectively correct the hallux valgus deformity with small surgical incision, high safety and curative effect, which is worthy of popularization and application in clinical.

In order to verify the correlation between Polygonum multiflorum-induced liver injury and HLA-B*35 : 01 alleles, six hospitalized patients diagnosed with Polygonum multiflorum-induced liver injury (PM-DILI) were selected, and their clinicopathological data were collected. Simultaneously, blood HLA-B* 35 : 01 allele detection was performed. Among the six PM-DILI cases, 4 were male, aged 38.83 ± 10.13 years old. The types of liver injury were hepatocellular injury types in all, and the severity of liver injury in five cases was grade 3. The histological presentations were acute hepatitis and acute cholestatic hepatitis. PM-DILI cases were all HLA-B*35:01 carriers, with a carrier rate of 100%. This finding indicates that PM-DILI is significantly correlated with HLA-B*35:01 alleles. Therefore, HLA-B*35 : 01 alleles can be used as an important predictive indicator for PM-DILI.