OBJECTIVE: To explore the surgical method and clinical efficacy of hip arthroplasty in the treatment of old non-union femoral intertrochanteric fractures. METHODS: Fifteen unoperated patients suffering from old non-union femoral intertrochanteric fractures from Feburary 2013 to Feburary 2023 were treated with hip arthroplasty including 9 males and 6 females, aged 71 to 82 years old. Eleven cases detected deep venous thrombosis(DVT), 9 cases received lower vena cava filter implantation. The operation time, intraoperative blood loss, intraoperative and postoperative blood transfusion, postoperative hemoglobin content, procedure-related complications, and the range of motion of hip flexion, abduction motion were recorded. The degree of hip pain was evaluated using a visual analogue scale(VAS). The hip Harris scores were used to evaluated the clinical efficacy. RESULTS: All patients were followed up for 3 to 12 months. The intraoperative blood loss was 200 to 400 ml, intraoperative blood transfusion was 0 to 400 ml, and the operation time was 40 to 90 min. All 15 patients had different degrees of anemia after surgery, the 3 days postoperative hemoglobin was 72 to 97 g·L^-1, and the postoperative transfusion volume was 0 to 400 ml. All patients had no periprosthetic infection, poor incision healing, lower limb deep vein thrombosis, and cerebral infarction. One case occurred in the early postoperative period, which disappeared from 4 to 5 days after operation, and there was no further revision at the last follow-up. The VAS was 6 to 7 points before operation and 2 to 4 points at latest follow-up;the hip Harris score was 2 to 13 points before operation and 73 to 84 points at latest follow-up. CONCLUSION The unoperated patients of old non-union femoral intertrochanteric fractures had significant clinical and imaging characteristics. Hip arthroplasty combined with or without femoral calcar reconstruction in the treatment of old non-union femoral intertrochanteric fractures had the advantages of relatively simple manipulation, rigid fixation, relatively safe operation, and relatively exact efficacy.
Humans ; Male ; Female ; Aged ; Hip Fractures/physiopathology* ; Aged, 80 and over ; Arthroplasty, Replacement, Hip/methods*

OBJECTIVE: To investigate the efficacy and safety of stanozolol combined with avatrombopag in the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients with relapsed/refractory tumors. METHODS: Twenty-five patients with relapsed/refractory CIT admitted to the Hematology Department of Xiyuan Hospital, China Academy of Chinese Medical Sciences between March 2023 to December 2023 were enrolled. These patients received a combined therapy of stanozolol and avatrombopag. The clinical efficacy, onset time, changes in platelet levels and blood cell counts before and after treatment, and adverse reactions of patients were evaluated. RESULTS: The combination therapy demonstrated remarkable efficacy with a total effective rate of 100%. Among the 25 patients, 19 achieved complete remission and 6 achieved partial remission. The median onset time was 42.5（range: 35-48）days. The average platelet count of the 25 patients increased from (25.73±17.75)×10⁹/L before treatment to (146.4±49.59)×10⁹/L after 3 months of treatment, with a statistically significant difference ( P < 0.05). 18 patients who previously required platelet transfusion were all weaned off platelet transfusion after 3 months of treatment, with a median time to be free from platelet transfusion was 26 (range: 18-51) days. During the treatment, both neutrophils and hemoglobin exhibited various degrees of elevation. Two patients experienced a slight increase in alanine aminotransferase(ALT) levels, which normalized after treatment with oral hepatoprotective drug. One patient had a PLT increase exceeding 350×10⁹/L, and the treatment with avatrombopag was suspended, and aspirin and other drugs were given to prevent thrombosis. No thrombose events or CIT-related bleeding events were observed in all patients. CONCLUSION The combination therapy of stanozolol and avatrombopag is significantly effective for treating relapsed/refractory CIT patients, with a high response rate and good safety, making it a suitable clinical treatment option.
Humans ; Thrombocytopenia/chemically induced* ; Stanozolol/therapeutic use* ; Male ; Female ; Neoplasms/drug therapy* ; Middle Aged ; Thiophenes/therapeutic use* ; Adult ; Platelet Count ; Treatment Outcome ; Antineoplastic Agents/adverse effects* ; Recurrence ; Thiazoles

OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

Objective To investigate the effect and mechanism of tetramethylpyrazine(TMP)on cognitive function in mice with post-traumatic stress disorder(PTSD).Methods The mice were randomly divided into normal group,model group and experimental group.Except for the normal group,the PTSD mouse model was established by single prolonged stress(SPS).The experimental group was intraperitoneally injected with 10 mg·kg-1 TMP,and the normal group and the model group were intraperitoneally injected with an equal amount of 0.9％NaCl.The Morris water maze,open field and elevated plus maze tests were used to evaluate the cognitive behavior of the mice.The apoptosis of neurons was detected by Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).The expression of ionized calcium binding adapter molecule-1(Iba-1)protein was detected by immunofluorescence(ICC).The content of oxidative stress inflammatory factors was detected by enzyme-linked immunosorbent assay(ELISA).Results The escape latency of the normal group,model group,and TMP group were(56.50±9.89),(87.16±10.48)and(68.63±10.19)s,respectively;the corner residence time of the open field were(190.37±40.64),(260.39±40.54)and(218.63±38.27)s,respectively;the apoptosis rates were(18.28±2.35)％,(39.36±3.65)％and(30.74±3.58)％,respectively;the fluorescence intensities of Iba-1 were(8.01±2.23)％,(50.87±7.31)％and(7.49±1.41)％;malondialdehyde contents were(5.46±0.95),(12.98±2.06)and(8.31±1.28)nmol·mg-1,respectively;tumor necrosis factor-α contents were(53.59±9.91),(115.46±11.53)and(74.38±10.77)pg·mL-1,respectively.The above indexes in the normal group and the experimental group were statistically significant compared with the model group(P＜0.05,P＜0.01).Conclusion TMP can improve the cognitive function of PTSD mice,and the mechanism may be related to the regulation of inflammation and oxidative stress.

OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

ObjectiveTo investigate the intervention mechanism of Dendrobium officinale leaf fermentation fluid in mice with alcoholic hepatitis. MethodsA total of 70 healthy male C57BL/6J mice， aged 6-8 weeks， were randomly divided into normal group， model group， liquid feed control group， silybin group， and low-， middle-， and high-dose Dendrobium officinale leaf fermentation fluid groups， with 10 mice in each group. The mice in the normal group were given normal diet， and those in the other groups were given Lieber-DeCarli classic liquid diet for 8 weeks to induce alcoholic hepatitis. During modeling， the mice in the low-， middle-， and high-dose Dendrobium officinale leaf fermentation fluid groups were given Dendrobium liquid manufactured by Warmen Pharmaceutical， and the mice in all the other groups were given pure water； the mice in the normal group， the model group， and the liquid feed control group were given normal saline by gavage， those in the silybin group were given silybin 0.25 mL/10 g by gavage， and those in the low-， middle-， and high-dose Dendrobium officinale leaf fermentation fluid groups were given Dendrobium officinale leaf fermentation fluid at a dose of 0.125 mL/10 g， 0.250 mL/10 g， and 0.375 mL/10 g， respectively， by gavage， once a day. At week 8， chloral hydrate was injected intraperitoneally for anesthesia， and blood samples were collected from the eyeball. After serum was separated， the biochemical method was used to measure the levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； HE staining and oil red staining were used to observe liver histopathology and lipid accumulation in mice； multiplex Luminex assay was used to measure the serum levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and CCL2； quantitative real-time PCR， Western blot， and immunofluorescence assay were used to measure the protein expression levels of NLRP3， caspase-1， caspase-11， gasdermin D （GSDMD）， N-terminal gasdermin D （GSDMD-N） in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of AST， ALT， IL-6， IL-1β， TNF-α， and CCL2 （all P<0.05）， and compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had significant reductions in the serum levels of AST， ALT， IL-6， IL-1β， TNF-α， and CCL2 （all P<0.05）. HE staining showed that the model group had disordered structure of hepatic lobules， with a large number of steatosis vacuoles and massive cell necrosis， and compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had alleviation of liver histopathological injury， intact structure of most hepatic lobules， and a small amount of inflammatory cell infiltration. Oil red staining showed that the model group had accumulation of large and small lipid droplets in the liver and a significant increase in liver fat content， and compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had significant alleviation of hepatic steatosis， with the presence of sporadic small lipid droplets. Immunofluorescence assay of liver tissue showed that compared with the normal group， the model group had a significant increase in the ratio of GSDMD-positive staining area in hepatocyte cytoplasm （P<0.001）， and compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had a significant reduction in such ratio in hepatocyte cytoplasm （P<0.001）. Quantitative real-time PCR showed that compared with the normal group， the model group had significant increases in the protein expression levels of NLRP3， caspase-1， caspase-11， GSDMD， GSDMD-N， interleukin-18 （IL-18）， and IL-1β in liver tissue （all P<0.05）， and compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had significant reductions in the protein expression levels of NLRP3， caspase-1， caspase-11， GSDMD， GSDMD-N， IL-18， and IL-1 （all P<0.05）. Compared with the model group， the high-dose Dendrobium officinale leaf fermentation fluid group had significant reductions in the protein expression levels of caspase-1 and caspase-11 （both P<0.05）， with a relative expression level of caspase-1 of 1.757 （reduced by 26.6% compared with the model group） and a relative expression level of caspase-11 of 0.455 （reduced by 70.3% compared with the model group）， suggesting that caspase-11 showed a greater reduction than caspase-1. ConclusionDendrobium officinale leaf fermentation fluid can alleviate alcoholic hepatitis in mice， possibly by inhibiting the non-classical cell pyroptosis pathway mediated by caspase-11.

Objective To establish an acute exposure model of extreme plateau hypobaric hypoxia environment and explore transcriptomic changes related to learning and memory impairment in rats.Methods Healthy male SD rats aged 6-weeks,200-250 g,were selected and divided into control group and plateau group.The control group was treated with normal pressure and oxygen(19 rats),and the plateau group was placed in a hypobaric hypoxia chamber(19 rats)at a simulated altitude of 8000 meters and treated for 72 hours.Behavioral changes were detected with 16 animals from each group using contextual fear conditioning and Morris water maze(8 rats each).Three hippocampal tissues were extracted from each group for transcriptomic sequencing,and the molecular mechanism of learning and memory impairment induced by extreme plateau environment was analyzed by Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)and gene set enrichment analysis(GSEA)enrichment.Results The behavioral result showed that compared with the control group,the fear memory and spatial learning memory abilities of rats in plateau group were decreased.GO and KEGG analyses showed that the extreme altitude environment reshaped the hippocampal microenvironment and affected the intercellular signal transmission,while GSEA analysis showed that the extreme altitude environment up-regulated the gene set related to the plasma membrane and extracellular matrix.Conclusion The extreme plateau environment at an altitude of 8000 meters could affect the microenvironment of rat hippocampus,destroy intercellular connections and impair intercellular communication and then induce learning and memory impairment.

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 investigate the effect of selenium on cyclophosphamide(CTX)-induced spermatogenic impairment(SI)in mice and its underlying mechanism.Methods:We equally randomized 36 male KM mice into 3 SI model and 3 control groups,the first 3 treated by intraperitoneal injection of CTX at 100 mg/kg(the SI model control group),CTX plus SI model control group,selenium deficient model group(-Se SI),selenium supplemented model group(+Se SI),while latter 3 by intraperitoneal injection of normal saline(the normal control),selenium deficiency control group(-Se control),selenium addition control group(+Se control),respectively,all once a week for 6 successive weeks.Then we observed the histopathological changes in the testes of all the mice by HE staining,obtained the sperm count in the epididymides,determined the expressions of glutathione peroxidase 4(GPx4)and SLC7A11 proteins by Western blot and ferroptosis-related genes by RT-qPCR,and examined the changes in the expres-sions of ferroptosis-related proteins and genes in the GC2-spd cells treated with ferroptosis inhibitors and inducers in combination with different concentrations of inorganic sodium selenite(SeS)and organic selenomethionine(SeM).Results:Compared with the nor-mal controls,the SI model mice showed significantly decreased testicular and prostatic organ coefficients,reduced spermatogenic lay-ers,increased voids,decreased serum ferritin concentration(P<0.05),and elevated transferrin concentration(P<0.05).The or-gan coefficients were significantly higher in the+Se SI and+Se control than in the-Se SI and-Se control groups(P<0.05,P<0.01),with evident pathological improvement of the testis tissue in the+Se controls.The expressions of the GPx4 and solute carrier family 7 members 11(SLC7A11)genes in the testis were dramatically down-regulated in the SI model controls(P<0.01),but up-reg-ulated in the+Se SI and+Se control compared with those in the-Se SI and-Se control group(P<0.01 and P<0.05),but there were no statistically significant differences between their protein expressions.The results of in vitro GC2 spd cell experiments indicated that the GPx4 gene and GPx4 protein levels in the-Se group were significantly lower than those in the normal control group(P<0.05),while the SLC7A11 gene level decreased(P<0.01).Different doses of SeS and SeM significantly increased the GPx4 protein expression compared to the average Se group.Low doses of SeM promoted a significant increase in GPx4 gene levels,while high doses of SeS increased the expression levels of SLC7A11 gene and SLC7A11 protein(P<0.05,P<0.01).The Se group showed a signifi-cant decrease in the levels of acsl4 and ptgs2 genes compared to the normal control group.SeM promoted the expression of acsl4,while SeS promoted the expression of ptgs2 and fth1(P<0.01,P<0.05).The intervention results of GC2 spd showed that the Erastin group had a decrease in ptgs2 compared to the normal control group,while the SeS+Erastin and SeM+Erastin groups had an increase in ptgs2 gene expression compared to the Erastin group.However,the ptgs2 expression of Fer-1 was lower than that of the normal con-trol group,and the ptgs2 gene level of SeS+Fer-1 and SeM+Fer-1 groups was lower than that of Fer-1 group(P<0.05);The gene quantity of GPx4 in the SeM+Erastin and SeM+Fer-1 groups increased compared to the Erastin and Fer-1 groups(P<0.01,P<0.05);SeM+Erastin and SeS+Erastin showed a decrease in SLC7A11 compared to the Erastin group,as well as SeM+Fer-1 and SeS+Fer-1 groups compared to the Fer-1 group,accompanied by an increase in acsl4 and fth1(P<0.01).Conclusion:Selenium deficiency causes the reduction of the SLC7A11 and GPx4 gene levels,disorder of ferroptosis-related genes and down-regulation of the GPx4 protein expression in the mouse testis and spermatocytes.Selenium can promote the expression of GPx4,up-regulate the level of SLC7A11,and improve spermatogenesis in the testis of the mouse with SI.There are differences between organic SeM and inorganic SeS in regulating the ferroptosis pathway-related genes.