OBJECTIVE To investigate the efficacy and safety of doxycycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia （MUMPP） in children under 8 years of age. METHODS The medical records of children with MUMPP admitted to the Women and Children’s Hospital Affiliated to Ningbo University were collected from January 1st， 2023 to December 31st， 2023. They were divided into doxycycline group （44 cases）， doxycycline combined with methylprednisolone group （35 cases）， and azithromycin combined with methylprednisolone group （35 cases） according to the treatment methods. Doxycycline group was given Doxycycline hyclate enteric-coated capsules； doxycycline combined with methylprednisolone group was given Doxycycline hyclate enteric-coated capsules and Methylprednisolone sodium succinate for injection； azithromycin combined with methylprednisolone group was given Azithromycin for injection and Methylprednisolone sodium succinate for injection. Treatment courses of 3 groups lasted for 10 d. The fever reduction rate， the time of fever reduction and improvement rate of lung infection absorption were compared among the three groups. The occurrence of adverse drug reactions was recorded during their hospitalization and followed up within 5 months after discharge. RESULTS The fever reduction rats 48， 72 h after treatment and improvement rate of lung infection absorption in doxycycline group and doxycycline combined with methylprednisolone group were significantly higher than azithromycin combined with methylprednisolone group； the time of fever reduction was significantly shorter than azithromycin combined with methylprednisolone group （P＜0.05）； there was no statistical significance in the difference between the doxycycline group and the doxycycline combined with methylprednisolone group （P＞0.05）. There was no statistical significance in the incidence of rash， vomiting， abdominal pain， diarrhea， and elevated transaminases among the three groups during hospitalization and within 5 months after discharge （P＞0.05）. None of the children treated with doxycycline suffered from tooth discoloration or enamel hypoplasia. CONCLUSIONS Doxycycline has good efficacy and safety in therapy of MUMPP in children under 8 years of age； adjunctive coadministration of low-dose glucocorticoids does not necessarily result in significant additional efficacy.

OBJECTIVE To elucidate the mechanisms responsible for the inhibitory effects of limonene on the proliferation of non-small cell lung cancer(NSCLC) by non-targeted metabolomics and additional approaches. METHODS The CCK-8 assay was utilized to evaluate the inhibitory effects of limonene on NSCLC A549 cell viability and to ascertain the IC50. In vitro experiments, encompassing colony formation, flow cytometry, iron content assessment, and mitochondrial staining, were conducted to assess the anti-lung cancer and iron-induced cell death effects of limonene. Metabolomic analysis was employed to identify potential pathways influenced by limonene, and Western blotting was carried out to validate pivotal proteins within these pathways. RESULTS In comparison to the control group, the limonene-treated group demonstrated a significant, dose-dependent reduction in A549 cell proliferation and colony formation. Optical microscopy revealed cellular detachment and pronounced changes in cellular morphology following exposure to limonene. Limonene induced apoptosis in A549 cells and arrested them in the G0-G1 phase of the cell cycle. Confocal microscopy unveiled diminished mitochondrial fluorescence and an augmented intracellular iron content, indicative of the classical phenomenon of ferroptosis. Metabolomic investigations unveiled divergent metabolic pathways, including glutathione(GSH) metabolism, arginine biosynthesis, D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism, with many of them intricately linked to intracellular GSH synthesis. Western blotting experiments underscored a marked reduction in the levels of SLC40A1, SLC7A11(xCT), and GPX4 proteins within the cells post-limonene treatment. CONCLUSION Limonene may induce ferroptosis in lung cancer cells by reducing GSH synthesis and increasing Fe2+ levels.

Objective:To evaluate the effect of perioperative application of hydroxychloroquine on the prognosis of patients undergoing cardiac surgery.Methods:All SLE patients in the Department of Cardiovascular Surgery of the First Affiliated Hospital of Zhengzhou University who took hydroxychloroquine and glucocorticoid for more than 7 days before operation were enrolled in the observation group(28 cases), including 3 males and 25 females, aged(38.3±8.2)years old. Patients who did not use hydroxychloroquine but only used glucocorticoid before operation were included in the control group(24 cases), including 2 males and 22 females, aged(37.9 ±9.8)years old. There was no significant difference in preoperative clinical data between the two groups in terms of sex, age, BMI, course of systemic lupus erythematosus, hemoglobin, albumin, C-reactive protein, ALT, serum creatinine, ejection fraction, diabetes, hypertension, hyperlipidemia, smoking, alcoholism, preoperative atrial arrhythmia, ventricular arrhythmia, atrioventricular block and so on. The constituent ratio of preoperative operation plan was basically the same between the two groups. The postoperative complications and survival of the two groups were compared.Results:There was no significant difference in early clinical indexes between the two groups, such as cardiopulmonary bypass time( t=0.12, P=0.19), chest drainage volume( t=0.30, P=0.77), second thoracotomy hemostasis( χ2=1.17, P=0.46). There was no significant difference in drug-related complications such as new retinopathy, myocardial concentric hypertrophy, atrial arrhythmia( χ2=1.27, P=0.26), ventricular arrhythmia( χ2=0.98, P=0.32), atrioventricular block( χ2=0.06, P=0.82) and other drug-related complications between the observation group and the control group. There was no significant difference between the two groups in postoperative acute heart failure( χ2=1.17, P=0.28), acute liver insufficiency( χ2=1.17, P=0.28), sternal infection and IABP use( χ2=0.47, P=0.50). Compared with the control group, the incidence of acute renal insufficiency after operation was lower in the observation group( χ2=4.51, P=0.04). The incidence of new postoperative pneumonia was lower( χ2=8.26, P=0.01). The length of postoperative antibiotic use, the length of postoperative ICU hospital stay, the postoperative hospital stay and the total cost of hospitalization in the observation group were significantly less than those in the control group( z=2.71, 2.09, 2.02, 2.02, P=0.01, 0.04, 0.04, 0.04). Compared with the control group, the in-hospital mortality rate of patients in the observation group was lower than that in the control group(3.6% vs. 12.5%, χ2=0.47, P=0.50), and the 6-month and 1-year survival rates of the observation group were higher than those of the control group(92.9% vs.83.3%, 92.9% vs.79.2%; χ2=0.41, 2.17; P=0.53, 0.34), but the difference was not statistically significant. Conclusion:Perioperative administration of hydroxychloroquine can significantly reduce the incidence of postoperative acute renal insufficiency and pneumonia, reduce the duration of postoperative antibiotic use, postoperative ICU hospital stay, postoperative hospital stay, and the cost of hospitalization. Hydroxychloroquine may reduce the in-hospital mortality and improve the long-term survival rate after cardiac surgery, but long-term large sample clinical studies are still needed.

Objective:To compare the clinical efficacy and safety of Shuo Tong ureteroscopy(ST-URS) and flexible ureteroscope(FURS)combined with holmium laser lithotripsy in the treatment of upper ureteral calculi with CT numerical value ≥ 1000 HU.Methods:A retrospective analysis of the clinical data of patients of upper ureteral calculi with CT numberical value≥1000 HU in the First Affiliated Hospital of Xiamen University was made from January 2018 to November 2020.There were 61 cases treated with ShuoTong ureteroscopy holmium laser lithotripsy (ST-URS group), including 45 males and 16 females, with 40 on the left and 21 on the right, age of(48.3±12.7) years, body mass index of(24.7±2.7)kg/m 2, the diameter of stone of(1.50±0.45)cm, and the CT numberical value of(1 288.8±179.0)(1 017-1 738)HU. There were 87 cases were treated with flexible ureteroscopy holmium laser lithotripsy (FURS group), including 58 males and 29 females, with 56 on the left and 31 on the right, age of(48.5±13.0) years, body mass index of(24.1±3.8)kg/m 2, the stone diameter of(1.45±0.40)cm, and the CT numberical value of(1 311.3±188.9)(1 009-1 817)HU. There were no significant differences in gender, age, body mass index, the location of stone, the diameter of stone and the CT numberical value of stone( P>0.05)between the two groups. For ST-URS group, a rigid ureteral channel sheath and standard mirror(F7.5/11.5)were placed under direct vision, exiting the standard mirror, leaving the channel sheath, inserting a lithotripsy mirror(F4.5/6.5)and a holmium laser[Power: 8-30 W(0.4-1.0 J/20-30 Hz)], and withdrawing the stone fragments after crushing the stone by "nibbling method" . For FURS group, a hard ureteroscope(F8/9.8)was used to explore the lesion side of the ureter, inserting a guide wire and placing a soft ureteral sheath, then inserting a flexible ureteroscope(F8)for holmium laser lithotripsy, and useing a stone basket to remove larger stone fragments. Ureteral stent was routinely indwelled after the operation. On the day 1 and 1 month after the operation, imaging examinations were performed to evaluate the stone-free rate. No residual stones or the diameter of stone was ≤0.4 cm and no urinary tract infection or any symptoms were defined as stone free. The operation time, blood loss, success rate of stage Ⅰ ureteral access sheath placement, incidence of postoperative complications, stone-free rate(SFR) at 1 day after operation, SFR at 1 month after operation, postoperative hospital stay and hospitalization costs were compared between the two groups. According to the size of calculi, the 2 groups were divided into 2 subgroups(≥1.5 cm and <1.5 cm)in order to make further analysis. The operation time, stone-free rate(SFR) at day 1 after operation and SFR at 1 month after operation were compared between the two groups. Results:The operation time of the ST-URS group was shorter than the FURS group(40.10 min vs. 49.43 min, P=0.020), and the incidence of postoperative complications was lower than the FURS group[3.28%(2/61)vs. 13.79%(12/87), P=0.031]. The SFR at day 1 after operation was significantly higher than the FURS group[60.7%(37/61)vs. 25.3%(22/87), P<0.01], and the hospitalization cost was lower than that of the FURS group(27 686 yuan vs. 32 281 yuan, P<0.010). There were no significant differences in the blood loss[(4.92±9.51)ml vs.(3.95±6.04)ml, P=0.452], success rate of stageⅠureteral access sheath placement[ 96.7%(59/61)vs. 96.6%(84/87), P=1.000], SFR at 1 month after operation[81.97%(50/61) vs. 75.86%(66/87), P=0.375] and postoperative hospital stay[(2.5±1.4)d vs.(2.4±0.8)d, P=0.543] between the two groups. When the size of calculi was ≥1.5cm, the operation time of the ST-URS group was shorter than the FURS group (43.67 min vs 55.00 min), the SFR at 1 day after operation was higher than the FURS group[40.00%(12/30)vs. 9.38%(3/32)], and the above differences are all statistically significant ( P<0.05). Conclusions:Compared with the FURS, for the treatment of upper ureteral calculi with CT numerical value ≥1000 HU, the ST-URS has shorter in operative time, lower in hospitalization cost and incidence of postoperative complications and higher SFR at day 1 after operation. The ST-URS is a safe and effective surgical technique, which is superior in the treatment of larger(≥1.5 cm) stones.

In recent years, the incidence of single-gene nephrolithiasis has been increasing year by year. With the application of whole-genome analysis and whole-exome sequencing technology, the etiology of single-gene mutations leading to the development of urinary calculi has been extensively verified. Therefore, this article reviews the research on urinary calculi-related genetic diseases at home and abroad, and introduces transport proteins and channels; ions, protons and amino acids. The role of urinary calculi in the majority of clinicians realizes the significance of genetic testing in such diseases, thereby increasing the understanding of genetically related urinary calculi and improving the level of clinical diagnosis and treatment.

Objective To explore the expression of ANLN in HCC and study the clinical value of ANLN expression for HCC patients after liver transplantation.Methods The protein and mRNA expression of ANLN was detected by immunohistochemistry and RNA-seq from TCGA respectively.Chi-square test and t test were used for correlation analysis between ANLN expression and clinicopathological characteristics.The predictive value of ANLN expression for HCC patients after liver transplantation was estimated by log-rank test and cox proportional hazards regression model.Results The positive protein expression rate of ANLN in HCC detected by immunohistochemistry was 37.0％ (34/92),significantly higher than 6.5 ％ (6/92) in para-carcinoma non-tumor tissue (P＜0.001,x2 =25.044).Upregulation of ANLN mRNA expression in HCC was also detected by the analysis of RNA-seq from the TCGA (P ＜ 0.000 1).The positive ANLN protein expression was positively correlated with AFP＞400 ng/L (P＜0.001,x2 =11.952) and tumor size ＞8 cm (P =0.034,x2 =4.506).The independent risk factors for poorer 5-year survival of patients after liver transplantation were confirmed,including positive ANLN protein expression (P =0.031,OR =1.965,95 ％CI =1.064-3.630),tumor size ＞8 em (P =0.003,OR =2.841,95 ％CI =1.437-5.617),worse differentiation degree (P =0.001,OR =3.613,95％ CI =1.646-7.928),peritumor intravascular cancer emboli (P =0.041,OR =1.896,95％CI =1.028-3.498) and tumor necrosis or hemorrhage (P=0.010,OR=2.195,95 ％CI=1.211-3.979).Conclusion The expression of ANLN in HCC is upregulated and the positive protein expression indicates the poor prognosis for long-term survival of patients after liver transplantation.

Objective To explore the clinical effect of embolectomy through incision of right atrium and inferior vena cava under normothermia cardiopulmonary bypass with beating heart + partial hepatectomy for hepatocellular carcinoma (HCC) combined with tumor thrombus in right atrium and inferior vena cava.Methods The retrospective and descriptive study was conducted.The clinical data of 1 patient with HCC combined with tumor thrombus in right atrium and inferior vena cava who were admitted to the Peking University People's Hospital in December 2014 were collected.The patient underwent embolectomy through incision of right atrium and inferior vena cava under normothermia cardiopulmonary bypass with beating heart + partial hepatectomy.Observation indicators:(1) intra-and post-operative situations:intraoperative findings,operation time,cardiopulmonary bypass time,volume of intraoperative blood loss,intraoperative blood transfusion,postoperative complication and duration of hospital stay;(2) postoperative pathological examination;(3) follow-up situation:survival of patient and tumor recurrence or metastasis.Follow-up using outpatient examination was performed to detect survival of patient and tumor recurrence or metastasis up to September 2016.Results (1) Intra-and post-operative situations size of tumor thrombus in right atrium,operation time,cardiopulmonary bypass time,volume of intraoperative blood loss,volumes of intraoperative red blood cell and blood plasma transfusions were 3.0 cm × 4.0 cm,630 minutes,85 minutes,4 000 mL,1 820 mL and 2 200 mL,respectively.The abnormal and transient liver and renal functions in early stage after surgery recovered quickly to the normal level.Patient with pleura1 effusion and pulmonary infection received active treatment,and then ventilator treatment was stopped at 5 days postoperatively and closed thoracic drainage-tube was removed at 15 days postoperatively.There was no occurrence of hemorrhage,bile leakage and wound infection.Patient was discharged from hospital at 25 days postoperatively.(2) Postoperative pathological examination:tumor with unclear boundary and gray-white section located in the right posterior lobe of the liver.Tumor thrombus in right atrium and inferior vena cava was gray-white,with a rough texture and size of 4.0 cm × 4.0 cm × 2.0 cm.Immunohistochemical staining dectection showed that liver cells,glypican 3 and CD34 were positive and alpha-fetoprotein was negative,with a positive index of Ki-67 of 15％.The moderate-differentiated HCC was confirmed by pathologic examination.(3) Follow-up situation:patient had a smooth recovery after discharge,without obvious discomfort.Hepatic arterial-venous fistula was confirmed at 45 days postoperatively by hepatic arterial angiography.Patient underwent preventive infusion chemotherapy with oxaliplatin and gemcitabine,and right hepatic arterial embolization with gelatin sponge.During the follow-up,patient received regular reexaminations of abdominal computed tomography and chest X-ray,without tumor thrombus in inferior vena cava and tumor recurrence.Conclusion Embolectomy through incision of right atrium and inferior vena cava under normothermia cardiopulmonary bypass with beating heart and partial hepatectomy are safe and feasible for patient with HCC combined with tumor thrombus in right atrium and inferior vena cava.

Vigorously development of the health service industry has received great attention,but the health service industry faces many difficulties.By analyzing the current predicament,this paper put forward the KY3H health care service model and systematically analyzed its six innovations:from "disease as the center" to "health as the center",from "homogenized group health service" to "Personalized and Humanized Health Service",from "Extensive Health Service"to "Precise Intervention of Individual Health Status",from "Single Health Service" to "Trinity Service of Health,Culture,Health Management and Health Insurance",from the "seeking medical" service model to "seeking one's own"service model,as well as from the "fixed (fixed-time,fixed-point,fixed-mode) service" to "anytime,anywhere full-time service".This model has achieved initial success in practice.It is an important way to solve the dilemma.

Objective To compare the differences of salivary alpha(α) amylase (sAA) activity and its activity ratio from the sali‐va before and after citric acid stimulation and approach the correlations among sAA activity determined by the methods of iodine‐starch ,Bernfeld and EPS‐G7 velocity respectively .Methods Ten saliva samples were collected from five healthy volunteers before and after citric acid stimulation .Their activities were determined three times by the three methods ,and the variation coefficient (CV) of sAA activity and activity ratio were calculated .Moreover ,correlation among sAA activities determined by the three meth‐ods were analyzed .Results The significant differences (P< 0 .05) were found in sAA activity and total CV from three determined methods ,and sAA activity and total CV by the method of EPS‐G7 velocity were minimum .There were no significant differences (P> 0 .05) in sAA activities ratio and its CV ;Significant correlation was found between sAA activity determined by random two of three methods(P < 0 .05) ,and their correlation coefficients were above 0 .96 .Conclusion The sAA activity data determined by three methods could be transformed each other by regression equation ,and determined precision by the method of EPS‐G7 velocity is highest ,and data processing method of sAA activity ratio could decrease differences among CV from three methods .

Objective To evaluate the effect of cisplatin on analgesia with morphine in rats with incisional pain.Methods Forty-two adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 6 groups (n =7 each) using a random number table:normal saline group (group C),normal saline + Pglycoprotein inhibitor LY335979 group (group CL),normal saline + morphine group (group CM),cisplatin group (group S),cisplatin + morphine group (group SM) and cisplatin + morphine + LY335979 group (group SML).Cisplatin 2 mg/kg was injected intraperitoneally once every two days for 5 times in S,SM and SML groups,while the equal volume of normal saline was injected intraperitoneally in C,CL and CM groups.At 2 days after the end of administration,the incisional pain models were established.At 10 min after establishing the model,normal saline 2 ml was injected subcutaneously in C and S groups; LY335979 20 mg/kg was injected via the caudal vein and normal saline 2 ml was injected subcutaneously in group CL; morphine 2 mg/kg was injected subcutaneously in CM and SM groups; LY335979 20 mg/kg was injected via the caudal vein and morphine 2 mg/kg was injected subcutaneously in group SML.Cumulative pain score was used to evaluate analgesia.Results Compared with group C,cumulative pain scores were significantly decreased in group CM,and no significant change was found in cumulative pain scores in CL and S groups.Compared with group CM,cumulative pain scores were significantly increased in group SM,and no significant change was found in cumulative pain scores in group SML.Cumulative pain scores were significantly lower in group SML than in group SM.Conclusion Cisplatin can weaken analgesia induced by morphine in rats with incisional pain through enhancing P-glycoprotein function in the blood-brain barrier.