ObjectiveTo investigate the effect of Gelian Tiaotang pills on renal fibrosis in db/db mice based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）/cysteinyl aspartate-specific proteinase （Caspase）-1/gasdermin D （GSDMD） signaling pathway. MethodsForty db/db mice were randomly assigned into model， positive control （0.001 3 g·kg·d^-1 dapagliflozin suspension）， and high-， medium-， and low-dose Gelian Tiaotang pills （3.12， 1.56， and 0.78 g·kg·d^-1 suspension of Gelian Tiaotang pills， respectively） groups， with 8 mice in each group. Eight db/m mice were selected as the normal group. The normal group and model group were given equal volumes of pure water， while the drug interventions groups were administrated with corresponding agents by gavage once a day for 12 consecutive weeks. The general conditions of mice were observed daily. The fasting blood glucose （FBG） and body mass were measured every 4 weeks. Kidneys were weighed after sampling， and the kidney index was calculated. An automatic biochemical analyzer was used to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The pathological changes， extracellular matrix deposition， and renal fibrosis degree were examined by hematoxylin-eosin， periodic acid-schiff （PAS）， and Masson staining， respectively. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin （IL）-1β and IL-18 in the renal tissue. Immunohistochemistry （IHC） was used to detect the localization and expression of fibronectin and collagen Ⅰ in the renal tissue. Western blot was employed to determine the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， and GSDMD-N in the renal tissue. ResultsCompared with the normal group， the model group generally had poor general states and increases in the body mass， kidney weight， kidney index， and levels of FBG， TG， TC， SCr， and BUN （P<0.01）. In addition， glomerular pyknosis， increased matrix， vacuolar degeneration of renal tubular epithelial cells， and interstitial infiltration of inflammatory cells were observed in the model group （P<0.01）， together with rises in the levels of IL-1β and IL-18 in the renal tissue （P<0.01） and up-regulated protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.01）. Compared with the model group， 12 weeks of drug interventions reduced the body mass， kidney weight， and kidney index and lowered the levels of FBG， TG， TC， SCr， and BUN in the serum and IL-1β and IL-18 in the renal tissue （P<0.05， P<0.01）. Furthermore， drug interventions ameliorated the renal lesions and down-regulated the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.05， P<0.01）. The high-dose group of Gelian Tiaotang pills had the best effects. ConclusionGelian Tiaotang pills may inhibit pyroptosis and reduce inflammatory responses by regulating the NLRP3/Caspase-1/GSDMD signaling pathway， thus delaying the process of renal fibrosis in diabetes.

ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease （DKD） in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose （FBG）. Mice with FBG ≥ 16.7 mmol·L^-1， increased urine output， and persistent albuminuria were considered successful in model establishment. After successful modeling， they were randomly divided into a model group， a dapagliflozin group （1.5 mg·kg^-1·d^-1）， and high， medium， and low dose groups of Dahuang Tangluo pills （3.6， 1.8， 0.9 g·kg^-1·d^-1， respectively）， with eight mice in each group. All medication groups were administered orally， while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks， the survival status of the mice was observed， and their body weight， FBG， and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products （AGEs） and receptors for advanced glycation end products （RAGE） proteins. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were utilized to detect the gene and protein expression levels of AGEs， RAGE， inhibitor of nuclear factor-κB （NF-κB） kinase （IKK）， and NF-κB in the renal tissues of mice in each group. ResultCompared with control group， the model group showed a significant increase in body weight， FBG， serum creatinine （SCr）， urinary microalbumin/urine creatinine ratio （ACR）， total cholesterol （TC）， and triglycerides （TG） （P<0.05）. The levels of intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） in renal tissues were significantly elevated （P<0.05）. Renal histopathological staining and electron microscopy revealed loose arrangement， gaps， structural disarray， mesangial proliferation， and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE， IKK， and NF-κB genes in renal tissues （P<0.05）. Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues （P<0.05）. Western blot results showed a significant increase in the expression of AGEs， RAGE， IKK， and NF-κB proteins in renal tissues （P<0.05）. After drug intervention， compared with model group， the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight， FBG， SCr， and ACR （P<0.05）， and a significant decrease in TC in mouse serum （P<0.05）， while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum （P<0.05）. All treatment groups showed a significant reduction in ICAM-1， IL-6， and TNF-α in renal tissues （P<0.05）. Renal histopathological staining and electron microscopy showed improved kidney injury， decreased collagen fiber deposition， and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE， IKK， and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Western blot results showed a significant decrease in the expression of AGEs， RAGE， IKK， and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice， possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

BACKGROUND:Congenital clubfoot mainly manifests as abnormal bone itself and abnormal cartilage development.The bone morphogenetic protein(BMP)/drosophila mothers against decapentaplegic protein(Smad)signaling pathway can direct the development of bone and cartilage during embryonic period,but its role in the field of clubfoot etiology has not been confirmed in animal experiments. OBJECTIVE:To explore the mechanism by which the BMP/Smad signaling pathway is involved in the regulation of foot and ankle chondroplasia in a rat congenital clubfoot model. METHODS:Sprague-Dawley rats at 10 days of gestation with the same growth condition were randomly divided into experimental and control groups.The experimental group was intragastrically given 135 mg/kg retinoic acid to make the clubfoot model,while the control group was given the same amount of vegetable oil.The fetal rats were taken out after 21 days of gestation by cesarean section.In the experimental group,the 27 of 41 fetal rats had clubfoot,with a deformity rate of 65.9%;in the control group,no clubfoot was observed in all the 36 fetuses.The ankles tissues of the rats were collected for hematoxylin-eosin staining.Western blot assay,RT-qPCR and immunohistochemistry were performed to detect the expression levels of Smad5 and P-Smad5,the core proteins of the BMP/Smad signaling pathway,as well as SP7 and Sox9,the downstream proteins of the BMP/Smad signaling pathway. RESULTS AND CONCLUSION:Compared with the control group,hematoxylin-eosin staining showed that the cartilage matrix in the foot and ankle tissues increased and the gap between the bones increased in the experimental group.Immunohistochemical findings showed that the expression levels of Smad5 and SP7 decreased in the experimental group,while the mRNA expression of Sox9 increased.RT-qPCR results showed that the mRNA expression of Smad5 and SP7 decreased,while the mRNA expression of Sox9 increased in the foot and ankle tissues of rats in the experimental group.Western blot results showed that P-Smad5/Smad5 expression and SP7 expression were decreased and Sox9 expression was increased in the ankle of rats in the experimental group.To conclude,the occurrence of cartilage abnormalities in the foot and ankle of the rat model of congenital clubfoot is associated with impaired transmission of the BMP/Smad signaling pathway.

AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.

Objective In order to clarify the identification path and the followed principles in this kind of pathological-related medical damage identification,explore the prevention and resolution ideas of pathological medical disputes in the medical and health departments,and build a path for the people's court to hear the cases of pathological medical injury liability disputes.Methods Taking the judgement of medical damage liability disputes that took effect in 2019-2023 and published on the judgement document network as a sample,conduct a retrospective analysis in terms of the site of lesion,medical fault,the consequences of the damage,the causal relationship and the degree of cause(degree of participation),the degree of accident classification and responsibility,the selection of appraisal method,and the acceptancde of appraisal opinions.Results From the analysis of the lesion site,there is a high proportion of misdiagnosis in breast,lung,thyroid,skin and uterus;from the analysis of medical fault,58.4%of delayed treatment and 41.6%of overtreatment due to improper selection of treatment plan;from the analysis of the consequences of damage,the consequences of death only account for about 20%.Most of them are in the category of living appraisal;from the analysis of responsibility division,medical institutions bear secondary reasons,accounting for 30.3%;from the analysis of appraisal and acceptance,medical damage identification methods are mostly used,and the court's acceptance of appraisal opinions reaches 92.1%.Conclusion(1)There are more pathological disputes involving women's bodies,and misdiagnosis is the most in the type of fault;(2)Forensic clinical professional appraisers can also participate in the identification of medical damage involving pathological diagnosis;(3)For cases of medical damage liability disputes involving pathological diagnosis and the consequences of death,the cause of death should be identified;(4)Medical damage identification should be in accordance with the principle of peer review.

OBJECTIVE: To investigate clinical effect of percutaneous reduction combined with internal fixation of calcaneal nail in treating Sanders typeⅡto Ⅲ calcaneal fractures. METHODS: From July 2017 to August 2019, clinical data of 98 patients with Sanders typeⅡto Ⅲ calcaneal fractures treated were retrospectively analyzed, and divided into observation group and control group according to different surgical methods. In observation group, there were 35 males and 21 females, aged from 23 to 58 years old with an average of (34.50±7.81) years old;29 patients with Sanders typeⅡand 27 patients with Sanders type Ⅲ;30 patients on the left side and 26 patients on the right side;the time from fracture to operation ranged from 1 to 4 days with an average of (3.45±0.54) days;and treated with percutaneous reduction combined with internal fixation of calcaneal nail system. In control group, there were 25 males and 17 females, aged from 25 to 60 years old with an average of (35.27±7.64) years old;23 patients with Sanders type Ⅱ and 19 patients with Sanders type Ⅲ;24 patients on the left side and 18 patients on the right side;the time from fracture to operation ranged from 2 to 5 days with an average of (3.42±0.62) days;and treated with open reduction and internal fixation. Operation time, blood loss, hospital stay, fracture healing time, and postoperative visual analogue scale (VAS) at 1 day, preoperative and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Böhler angle, Gissane angle and calcaneus width, and postoperative complications were compared between two groups. RESULTS: All patients were followed up from 13 to 18 months with an average of (15.6±2.2) months. There were significant differences in operation time, blood loss, hospital stay, fracture healing time and postoperative VAS at 1 day between two groups (P<0.05). There was statistical difference in postoperative AOFAS score at 12 months between two groups (P<0.05), and AOFAS score at 12 months after operation was higher than that before operation (P<0.05). According to AOFAS score, 21 patients got excellent result, 30 good and 5 moderate in observation group, and 10 excellent, 22 good, 7 moderate and 3 poor in control group, which had statistical difference between two groups (P<0.05). Postoperative Böhler angle, Gissane angle and calcaneus width at 6 months were better than that before operation between two groups(P<0.05). One patient in observation and 20 patients in control group occurred skin numbness after operation, and 14 patients occurred skin necrosis in control group, there were obvious difference between two groups(P<0.01). CONCLUSION Compared with open reduction and internal fixation, percutaneous reduction combined with internal fixation system in treating Sanders typeⅡto Ⅲ calcaneal fractures is feasible for fracture repair without waiting for foot deswelling, which could accurately restore normal shape and position of the fractured heel bone, completely eliminate fracture malunion, and reduce postoperative complications. Therefore, it could shorten operation time, hospital stay, fracture healing time, reduce amount of blood loss, promote postoperative recovery, and less complications, high safety, which could be used as a choice of orthopedic surgery for foot and ankle trauma.
Male ; Female ; Humans ; Infant, Newborn ; Calcaneus/injuries* ; Retrospective Studies ; Treatment Outcome ; Fractures, Bone/surgery* ; Fracture Fixation, Internal ; Ankle Injuries ; Bone Screws ; Foot Injuries ; Knee Injuries ; Ankle Joint ; Postoperative Complications

【Objective】 To investigate the resource allocation status of blood testing laboratories in 14 blood stations in Gansu Province, explore the impact of differences in basic conditions on the comprehensive testing ability of laboratories, so as to promote the homogenization and standardization of blood screening capacity in blood stations in Gansu and improve blood safety and effectivenes. 【Methods】 An evaluation index system of laboratory resource allocation was constructed and a question-naire was designed. The data of human resources, infrastructure and key equipment of 14 blood stations were collected. The entropy weight -TOPSIS method was used to evaluate and rank the resource allocation of 14 blood stations. 【Results】 In the comprehensive evaluation of blood testing laboratory resource allocation in 14 blood stations in Gansu, the top three were laboratories A, B and I, and the last three were laboratories G, M and J. On the whole, the main issue was unreasonable structure of human resources: most laboratories had unreasonable age structure; except for Laboratory A, there was no personnel with bachelor's degree or above in laboratories; most laboratories had not established a team with intermediate professional titles. In terms of infrastructure, the size of seven laboratories could not meet the needs of modern laboratory testing, and all eight blood stations had no spare nucleic acid laboratories nor a mutual spare laboratory with other blood stations As for the key equipment, 5 laboratories had no automatic blood grouping diagnostic instrument, 5 laboratories only had one set of enzyme immunoassay detection system, 3 laboratories had no spare equipment for the key equipment, which means if the equipment failure could not be repaired in time, the release of results would be affected. 【Conclusion】 There were significant differences in human resources, infrastructure and key equipment of blood testing laboratories in 14 blood stations in Gansu, which had a great impact on laboratory testing capacity and subsequent development. It is suggested that governments at all levels and health administrative departments optimize the input of laboratory resource allocation according to the blood collection volume of blood stations to gradually narrow the differences in resource distribution between different regions, improve the degree of laboratory automation and optimize the personnel structure, so as to build high-quality and efficient blood testing laboratories and ensure the safety of clinical blood use.

Objective To investigate the prevalence of ASCVD in adult with type 2 diabetes (T2DM) in Tianshui City and assess the incidence risk in the next 10 years, so as to provide a theoretical basis for the prevention and treatment of ASCVD. Methods A total of 904 T2DM patients aged 20~88 years admitted in the cardiology department of Tianshui Hospital from May 2018 to June 2022 were grouped according to physical index (BMI), blood pressure, triglyceride (TG) ，glycosylated hemoglobin (HbA1c) and serum levels of asprosin and the risk of ASCVD by China-PAR model. Results The prevalence of ASCVD in adults with T2DM was 36.06%, and there were significant differences in the prevalence of ASCVD between different gender, hypertension grade, BMI and serum albumin (P<0.05).China PAR risk prediction model shows that the risk of ASCVD in 10 years increases with the increase of BMI, hypertension stage, serum albumin and HbA1c levels; the number of high-risk ASCVD patients in the next 10 years will increase with male, abnormal BMI, the increase of serum albumin and TG expression levels, and the difference was statistically significant (P<0.05). The results of multiple logistic regression showed that the risk factors of ASCVD in 10 years were serum white adipose level>310 pg/mL （OR=2.873, 95% CI:2.332-4.103), grade 3 hypertension （OR=1.726, 95% CI:1.281-1.981) and BMI>24（OR>1.5）. Conclusion The occurrence of ASCVD in T2DM patients is related to a variety of factors , it is very important to control the serum albumin , BMI , hypertension to reduce the incidence rate of ASCVD within 10 years.

Hoffa fracture is an unstable intra-articular fracture with significant redisplacement tendency. It is easy to be missed diagnosis when accompanied by distal intercondylar or supracondylar fracture of femur. CT scan is the gold standard for the diagnosis of Hoffa fracture. The treatment principles are anatomic reduction of the articular surface, reliable internal fixation, and early functional activity. At present, the main treatment is arthroscopic screw fixation. During screw fixation, the tail cap of screw should be buried, resulting in non-healing iatrogenic injury of articular cartilage. In the early postoperative functional activity of knee joint, fracture block was repeatedly subjected to backward and upward shear force under the action of the tibial plateau, which is the main reason for the failure of internal fixation. Plate assisted screw fixation could increase local mechanical stability, but it still cannot avoid the defects of iatrogenic cartilage injury. At the same time, plate molding is required during the operation due to the absence of special anatomical plates, resulting in increased surgical trauma and time-consuming surgery. The ideal fixation method for Hoffa fracture should include:(1) Avoid iatrogenic injury of articular surface cartilage. (2) With the rear anti-shear barrier plate function.(3) The internal fixator is closer to the load interface, so as to obtain greater load and better fixed strength.
Humans ; Hoffa Fracture ; Femoral Fractures/surgery* ; Tomography, X-Ray Computed ; Fracture Fixation, Internal/methods* ; Bone Plates ; Iatrogenic Disease

ObjectiveTo observe the efficacy and safety of sertraline combined with low-dose olanzapine in the treatment of depression and anxiety comorbidity and its effect on sleep quality， so as to provide references for the related clinical treatment. MethodsA total of 121 patients who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） for depressive episode and generalized anxiety disorder in The Third People's Hospital of Tianshui and the Sanatorium for Mental Illness of Veterans in Tianshui from October 2019 to August 2020 were enrolled， and they were divided into two groups according to the random number table method. Study group （n=61） received sertraline combined with low-dose olanzapine， while control group （n=60） received sertraline only. Then the disease severity degree， sleep quality and adverse reactions were assessed using Hamilton Depression Scale - 17 item （HAMD-17）， Hamilton Anxiety Scale （HAMA）， Pittsburgh Sleep Quality Index （PSQI） and Treatment Emergent Symptom Scale （TESS） at the baseline， 1^st， 2^nd， 4^th， 6^th and 8^th weekend， respectively. ResultsPost-treatment HAMD-17， HAMA and PSQI scores in both groups were lower than those before treatment （P<0.05）. At each time point after treatment， HAMD-17， HAMA and PSQI scores of study group were lower than those of control group， with statistical significance （P<0.05）. ConclusionSertraline alone and its combination with low-dose olanzapine are both effective in the treatment of depression and anxiety comorbidity， while the combination therapy achieves better efficacy and higher safety in alleviating anxiety and insomnia symptoms.