ObjectiveTo establish steroid-induced osteonecrosis of the femoral head （SANFH） cell model by using dexamethasone （DEX）-induced bone marrow mesenchymal stem cells （BMSCs） and demonstrate that Gushing Granules （GSNs） exert an improving effect by activating the phosphatidylinositol-3-kinase/protein kinase B/B-lymphoma-2 gene related promoter （PI3K/Akt/Bad） signalling pathway. MethodsFirstly， SD rats were orally administered with drugs at a dose of 0.9 g·kg^-1 to prepare GSN-containing serum， and CCK-8 screening was used to determine the optimal dosage and duration of action. Then， BMSCs were cultured and treated with 1×10^-6 mol·L^-1 DEX， 10% GSN-containing serum， and inhibitor LY294002 of PI3K/Akt signalling pathway for 24 hours to model and group SANFH cells. Cell viability and proliferation were detected by using CCK-8 assay kit and EdU staining kit. Flow cytometry was used to detect cell apoptosis. An alkaline phosphatase （ALP） assay kit was employed to detect ALP expression. In order to detect the PI3K/Akt/Bad signalling pathway and protein and mRNA expression of apoptosis-related proteins such as apoptosis regulatory factors B-cell lymphoma-2 gene （Bcl-2）， and Bcl-2-associated X protein （Bax）， osteocalcin （OCN）， and Collagen Ⅰ， we used Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsThe CCK-8 assay kit determined that the optimal dosage for GSN-containing serum is 10%， and the duration of action is 48 hours. After modelling and grouping the cells in each group， the detection results showed that the SANFH model group had significantly lower cell viability， cell proliferation， and ALP expression， as well as protein and mRNA expressions of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen I compared to the blank group. The nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly increased （P<0.05，P<0.01）. After treatment with GSN-containing serum， cell viability， cell proliferation， and ALP expression， as well as expressions of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen Ⅰ nucleic acids and proteins were significantly increased， while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly decreased（P<0.05，P<0.01）. Compared with the GSN drug-containing serum group， the simultaneous treatment with the inhibitor LY294002 and GSN drug-containing serum reversed the improvement effect of GSN. Specifically， the cell viability， cell proliferation， ALP expression， and the nucleic acid and protein levels of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen Ⅰ were all significantly decreased， while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry were significantly increased （P<0.05， P<0.01）. ConclusionGSNs antagonize DEX-induced apoptosis of BMSCs by activating the PI3K/Akt/Bad signalling pathway， providing a scientific theoretical basis for the clinical treatment of SANFH with GSNs.

To summarize the clinical experience and characteristics of Professor XU Xin in syndrome differentiation and treatment of polycystic ovary syndrome with insulin resistance （PCOS-IR）. XU Xin believes that the etiological factors of PCOS-IR is qi deficiency of the spleen and kidney， and the key disease mechanism is dysfunction in transportation and transformation of spleen and kidney， causing phlegm dampness and turbid heat accumulated in yangming， then evolving into the lower jiao， mixed with blood stasis， finally obstructing the chong （冲） and ren （任） mai and uterus. So in clinic， the method of boosting the kidney and fortifying the spleen was used through out the whole treatment commonly using modified Shoutai Pill （寿胎丸） and Sijunzi Decoction （四君子汤）. The main therapeutic method for treating PCOS-IR refers to clearing and draining dampness heat in yangming， invigorating blood and regulating period， with self-prescribed Yishen Quzhuo Formula （益肾祛浊方）， as a reference for the treatment of this disease.

Objective To investigate the epidemiological characteristics of local visceral leishmaniasis in Beijing Municipality from 2021 to 2023, so as to provide insights into formulation of the visceral leishmaniasis control strategy. Methods Epidemiological data of visceral leishmaniasis cases reported in Beijing Municipality from 2021 to 2023 were collected from the National Health Informatization Disease Prevention and Control Information System, and the epidemiological characteristics of local visceral leishmaniasis cases were analyzed using a descriptive epidemiological method. In November 2021 and 2023, 50 to 100 permanent residents were voluntarily selected within a 100 meter radius of sites where patients lived or acquired Leishmania infections, and venous blood was sampled for anti-Leishmania antibody testing. Venous blood was sampled from dogs for anti-Leishmania antibody testing in natural villages where patients lived or acquired Leishmania infections, or in districts where Leishmania infected dogs were reported. In addition, sandflies were captured with CO₂ mosquito traps and fine mesh nets in natural villages where patients lived or acquired Leishmania infections from May to September, 2021 and 2023, for sandfly species identification. Results A total of 4 local visceral leishmaniasis cases were reported in Beijing Municipality from 2021 to 2023, with ages of 2 to 77 years, and acquiring Leishmania infections in Mentougou District (2 cases), Changping District (1 case), and Yanqing District (1 case). The anti-Leishmania antibody testing was all negative in 73 human blood samples and the sero-prevalence of anti-Leishmania antibody was 25.00% in 36 venous blood samples from domestic dogs in 2021, with a total of 4 520 Phlebotomus chinensis captured. The sero-prevalence of anti-Leishmania antibody was 0.51% in 198 human blood samples and 13.58% in 243 venous blood samples from domestic dogs in 2023, with 16.10%, 25.00%, 17.78% and 3.13% sero-prevalence in dogs sampled from Mentougou District, Changping District, Yanqing District and Haidian District, respectively (P = 0.011), while a total of 1 712 Ph. chinensis were captured, including 1 421 female sandflies (86.54%). Conclusions The prevalence of local visceral leishmaniasis was low in Beijing Municipality from 2021 to 2023; however, there is a risk of further spread in the epidemic foci. Intensified visceral leishmaniasis surveillance and control is recommended.

AIM:To investigate the mechanism of chronic stress-induced myocardial injury in atherosclerotic(AS)mice.METHODS:Eight-week-old SPF-grade male ApoE-/-mice and C57BL/6J mice used in this study.The mice received dietary intervention for 10 weeks followed by pathological examination to test the successful AS modeling.After AS establishment,the mice were exposed to chronic unpredictable mild stress(CUMS)for 6 weeks and then divided into five groups:control,CUMS,AS-regular diet(AS-r)+CUMS,AS-high-fat diet(AS-h),and AS-h+CUMS.During CUMS,open-field test and sucrose preference test were performed on mice in all groups.Blood lipids were characterized using an automatic biochemical analyzer.Hematoxylin-eosin(HE)and oil red O staining were performed to evaluate pathological changes in the aortic root.Cardiac function was assessed using echocardiography.The serum concentration of myocardial injury markers and ATP content was detected by ELISA.Transmission electron microscopy was employed to observe the ul-trastructure of myocardial mitochondria.Myocardial mitochondrial oxygen consumption rate was determined using the Oxy-graph-2k high-resolution respiratory energy metabolism analyzer.Western blot was conducted to quantify the expression of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and cleaved caspase-3.RESULTS:compared with the Control group,the total distance traveled,the number of entries into the central area,and the sucrose preference rate were significantly decreased in all CUMS groups(P<0.05).All AS groups exhibited varying levels of lipid deposition and endo-thelial damage in the aortic root,along with a significant reduction in cardiac function(P<0.05)and varying degrees of myocardial injury(P<0.05).In the AS-h+CUMS and AS-r+CUMS groups,myocardial mitochondrial structure was signifi-cantly disrupted.ATP content was significantly reduced(P<0.05),and the rates of oxygen consumption associated with mitochondrial respiratory chain complex I,mitochondrial respiratory chain complexes I+II,and the maximum respiratory capacity of the electron transport system were all significantly decreased(P<0.05).Moreover,the protein levels of Bax and cleaved caspase-3 were significantly increased(P<0.05),while that of Bcl-2 protein was significantly decreased(P<0.05).CONCLUSION:Chronic stress triggers mitochondrial non-steady-state load by disrupting myocardial structure and energy metabolism in AS mice,promoting myocardial cell apoptosis and myocardial injury.

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

Objective    To analyze the results and rationality of the lesion-focused strategy with subsegment as the pulmonary anatomical unit for pulmonary nodules with a diameter of ≤2 cm which require surgery. Methods    Clinical data of 246 patients with pulmonary nodules who underwent surgery in the Department of Thoracic Surgery of The First Affiliated Hospital of Nanjing Medical University from January 2017 to October 2018 were retrospectively analyzed, including 76 males and 170 females, with an average age of 53.30±11.82 years. The patients were divided into four groups, a single segmentectomy group, a segmentectomy combined with adjacent subsegmentectomy group, a single subsegmentectomy group and a combined subsegmentectomy group, according to the different surgical approaches, to compare preoperative, intraoperative, and postoperative related data. Results    There was no perioperative death. Among the four groups, there was no statistical difference in gender (P=0.163), age (P=0.691), diameter of the nodule (P=0.743), longitudinal position of the nodule (depth ratio, P=0.831), postoperative pulmonary leakage (P=0.752), intraoperative blood loss (P=0.135), pathological type (P=0.951) or TNM stage (P=0.995); there were statistical differences in transverse position of the nodule (P<0.001) and number of subsegments involved (P<0.001). The results of multivariate logistic regression analysis showed that compared with combined subsegmentectomy, the odds ratio (OR) of the lung nodule in segmentectomy combined with adjacent subsegmentectomy as intersegment nodules was 5.759 (95%CI 1.162 to 28.539, P=0.032). Conclusion     The surgical strategy of lesion  focused and subsegment as anatomical unit is safe and feasible for surgical treatment of pulmonary nodules with diameter ≤2 cm. The transverse position of the nodules is an important factor affecting the choice of surgical method for the middle and lateral nodules with a diameter of ≤2 cm, and the longitudinal location of the nodule is not an influencing factor. For nodules in inner zone, the diameter also is one of the factors influencing the choice of surgical method.

Objective    To analyze the incidence and drainage pattern of the specific collateral vein (VL) located between several adjacent segments of the bilateral upper lung, and its clinical significance in the surgical treatment of early lung cancer. Methods    The preoperative three-dimensional computed tomography bronchography and angiography (3D CTBA) data of 1 515 patients in the First Affiliated Hospital of Nanjing Medical University from 2017 to 2020 were analyzed retrospectively, including 524 males and 991 females, with an average age of 54.27±11.43 years. There were 712 patients of right upper lung and 803 patients of left upper lung. The incidence and drainage pattern of VL in bilateral upper lungs were analyzed. Furthermore, the imaging data and medical records of 113 patients in the left upper lung were reviewed to investigate the influence of the relative position relationship between nodules and VL on the selection of operation. Results    The overall incidence of VL was 72.7% (1 102/1 515) in the bilateral upper lungs, including 68.0%(484/712) in the right upper lung, and 77.0% (618/803) in the left upper lung. The incidence of VL in the left side was significantly higher than that in the right side (P<0. 05). VL mainly drained into V2a+b (327/484, 67.6%) in the right upper lung and into V1+2b+c (389/618, 62.9%) in the left upper lung. When the spherical simulative cutting margin of 2 cm of the nodule did not involve VL, it was more feasible to undergo sublobectomy than those whose simulative cutting margin of 2 cm involved VL, and the difference was statistically significant (91.9% vs. 61.5%, P<0.05). When the spherical simulative cutting margin of 2 cm of nodule involved VL, the lesion located in the middle or inner zone was more feasible to undergo lobectomy than that in the outer zone, but the difference was not statistically significant (43.8% vs. 34.8%, P>0.05). Multivariate logistic regression analysis showed that diameter of the lesion, whether the spherical simulative margin of 2 cm involving VL and the depth ratio of the lesion were independent risk factors affecting the surgical options (P<0.05). Conclusion    The incidence of the specific collateral vein in bilateral upper lungs is high, and the drainage pattern is diverse, which has important guiding significance for preoperative planning and intraoperative manipulation. For deep nodules adjacent to VL, lobectomy or resection of left upper division is often performed to ensure a safe margin.

Objective To investigate the features and characteristics of GLIS3 gene mutation in patients with congenital hypothyroidism(CH),and to establish the theoretical basis for gene diagnosis and prenatal diagnosis of CH.Methods Genomic DNA was extracted from peripheral blood leukocytes of 50 patients with CH who were collected from February 2007 to November 2016 in Shandong Province.The exon 2 to 11 of GLIS3 were amplified with 11 pairs of sequence specific primers designed by Primer 5.0.Polymerase chain reaction and the first generation of sequencing method(Sanger sequencing) were used to detect the mutation.Comparison of the sequencing results with the GLIS3 reference sequence (National Center for Biotechnology Information Reference Sequence:NC_000009.12) helped to screen gene mutations.Results The 50 CH patients included 22 boys and 28 girls,and the sex ratio was 1.0 ∶ 1.3.The mean age was (2.5 ± 0.5) years.Six cases (12％) had thyroid gland hypoplasia,23 cases (46％) had thyroid gland agenesis and 21 cases(42％) with ectopic thyroid gland.C2507A missense mutation was found in exon 10 of GLIS3 in a thyroid gland agenesis case,which might result in proline to glutamine substitution at codon 836.One mutant (rs780019691,c.C289T) was detected which was nonsense mutation (Arg→Stop) in another thyroid gland agenesis child.Conclusions The mutation rate of GLIS3 gene is very low in CH children of Shandong province.Further studies are needed to investigate the relationship between GLIS3 genotypes and clinical phenotypes.

Objective To investigate the effects of laryngeal mask airway combined with lung-protective ventilation on postoperative pulmonary complications in patients undergoing open abdominal surgery with general anesthesia.Methods Eighty-seven patients of both sexes,aged 18-64 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective open abdominal surgery under general anesthesia,were randomly divided into 2 groups:endotracheal intubation plus routine ventilation group (group IC,n =43) and laryngeal mask airway plus protective ventilation group (group LP,n =44).In group IC,single lumen endotracheal tube was inserted and the patients were mechanically ventilated,with inhaled pure oxygen 2 L/min,tidal volume 8-10 ml/kg,respiratory rate 8-12 breaths/min,inspiratory/expiratory ratio 1 ∶ 2.In group LP,the ProSeal laryngeal mask airway was inserted and lung-protective ventilation was performed,with inhaled pure oxygen 2 L/min,tidal volume 6-8 ml/kg,respiratory rate 12-16 breaths/min,inspiratory/expiratory ratio 1 ∶ 2,positive end-expiratory pressure 5 cm H2O,and recruitment maneuvers was performed manually every 30 min during operation.End-tidal pressure of carbon dioxide was maintained at 35-45 mmHg.The development of pulmonary complications such as pneumonia,pleural effusion,pulmonary atelectasis,pneumothorax,bronchospasm and acute respiratory failure was recorded within 7 days after surgery.Results Pulmonary atelectasis,pneumothorax or acute respiratory failure was not found in the two groups.Compared with group IC,no significant change was found in the incidence of pneumonia,pleural effusion and bronchospasm after operation (P＞0.05),and the total incidence of postoperative pulmonary complications was significantly decreased in group LP (P＜0.05).Conclusion Compared with endotracheal intubation and conventional ventilation,laryngeal mask airway combined with lung-protective ventilation can reduce postoperative pulmonary complications in the patients undergoing open abdominal surgery with general anesthesia.

Objective To investigate the relationship between blood vessel invasion (BVI) and clinicopathologic features and prognosis in patients with gastric cancer,and analyze related factors affecting the prognosis of patients.Methods The clinicopathological data of 206 patients with gastric cancer who were admitted to the Nanjing Hospital Affiliated to Nanjing Medical University from January 2007 to December 2010 were retrospectively analyzed.The BVI of surgical tumor specimens in all patients was detected by immunohistochemical staininng.All the patients were followed up via outpatient examination and telephone interview up to March 2014.The count data were analyzed using the chi-square test.The survival curve was drawn by Kaplan-Meier method.The survival analysis and univariate analysis were done using the Log-rank test,and multivariate analysis was done using the COX regression model.Results The BVI rate of 206 patients was 27.67％ (57/206).The BVI rate of tumor tissues,tumor differentiation,perineural invasion,T stage,N stage and TNM stage in all patients with gastric cancer were compared,showing significant differences (x2=14.396,9.569,15.579,43.453,30.732,P ＜ 0.05).After operation,188 patients were followed up for 6.0-60.0 months (median,34.0 months),with the follow-up rate of 91.26％ (188/206).Among 188 patients with follow-up,the median survival time and 5-year cumulative survival rate in patients with BVI and with negative BVI were 32.4 months and 19.6％,40.7 months and 42.0％,respectively,with a significant difference in the survival of patients (x2 =9.364,P ＜ 0.05).The results of univariate analysis showed that the diameter of tumor,tumor differentiation,perineural invasion,BVI,T stage,N stage and TNM stage were factors affecting the prognosis of patients with gastric cancer (x2=9.241,17.486,11.243,9.364,27.666,216.745,49.887,P ＜ 0.05).The results of multivariate analysis showed that the diameter of tumormore than 5 cm,BVI,stage T4,stage N3 and stage Ⅲ were independent risk factors affecting the prognosis of patients with gastric cancer (HR =0.502,0.456,0.052,0.001,0.735; 95％ confidence interval:0.334-0.754,0.289-0.720,0.004-0.664,0.000-0.006,0.159-3.398,P ＜ 0.05).Conclusions BVI in patients with gastric cancer is associated with the progression of tumors.The diameter of tumor more than 5cm,BVI,stage T4,stage N3 and stage Ⅲ are independent risk factors affecting the prognosis of patients with gastric cancer,and BVI may be a predictor of poor prognosis of patients with gastric cancer.