AIM:To analyze the compliance rate and possible influencing factors for blood concen-tration of meropenem in patients with central ner-vous system(CNS)infections,and to provide basis for optimizing the administration of meropenem in the patients.METHODS:A retrospective analysis was performed in patients who were treated with meropenem and monitored the concentration(Cmin)from January 2021 to December 2022.The basic clinical data of the patients were recorded,and the achievement of meropenem blood concentration was counted.Univariate and binary logistic regres-sion analysis were used to analyze the influencing factors for the e substandard steady-state blood trough concentration of meropenem.The ROC curve was drawn to predict the clinical characteris-tics.RESULTS:Forty-five cases were included.The median Cmin of meropenem was 4.14(0.82,16.29)mg/L,and 51.11％reached the target range with 4 mg/L.Binary logistic regression analysis showed that serum creatinine value and using mannitol were risk factors for the substandard steady-state blood trough concentration of meropenem(P＜0.05).When serum creatinine value was less than 84 μmol/L,the area under the ROC curve was the largest(0.916),the sensitivity was 0.783,the speci-ficity was 0.955,and the Youden index was 0.738.CONCLUSION:The Cmin compliance rate of merope-nem blood concentration in patients with CNS in-fection is low,especially in patients with hyperfunc-tion of kidney and those who using mannitol.It is necessary to conduct drug concentration monitor-ing to optimize the administration of meropenem in patients with CNS infection.

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 mediating effect of inflammatory factors in the association between low density lipoprotein-cholesterol(LDL-C) and thyroid associated ophthalmopathy(TAO).Methods:This study was a prospective study, which icluded a total of 86 patients with Graves′ disease who attended the Department of Endocrinology of the First Affiliated Hospital of Zhengzhou University from January 2021 to June 2022. Among them, there were 56 patients with Graves′ disease accompanied by TAO, including 30 cases in the inactive group and 26 in the active group. Additionally, there were 30 cases having Graves′ disease alone. The relationship between LDL-C, inflammatory factors, and the onset and activity of TAO were analyzed using binary logistic regression. Mediation analysis was used to explore the mediating effect of inflammatory factors in the association between LDL-C and TAO onset and activity.Results:Interleukin(IL) -6 was a potential mediator that linking the association between LDL-C and TAO onset: LDL-C had a direct effect on TAO(Total effect value=0.274, 95% CI 0.161-0.386), while IL-6(mediated effect=0.067, 95% CI 0.011-0.123) and IL-17(mediated effect=0.042, 95% CI 0.007-0.077) partially mediated the effect of LDL-C on TAO, accounting for 24.45% and 15.33% of the total effect, respectively. IL-6 was a potential mediator of the association between LDL-C and TAO activity: LDL-C had a direct effect on TAO activity(Total effect value=0.320, 95% CI 0.204-0.435), and IL-6(mediated effect=0.103, 95% CI 0.021-0.185) partially mediated the effect of LDL-C on TAO activity, with a mediation effect of 32.19%. Conclusion:IL-6 plays a partiall mediating role in the association of LDL-C with TAO onset and activity.

Objective:To investigate the effects and potential mechanism of vitamin D supplementation on testicular function in aging rats induced by D-galactose.Methods:The aging rats were induced by D-galactose with subcutaneous injection. The animals were randomly divided into 6 groups: aging rats (DG), aging rats with low-dose vitamin D supplementation (LD), aging rats with high-dose vitamin D supplementation (HD), normal control rats(NC), normal rats with low-dose vitamin D supplementation(LN), normal rats with high-dose vitamin D supplementation (HN). The body weight, testicular weight, serum testosterone concentrations and sperm quality of the rats in each group were measured. The testis morphological changes were detected using light microscopy. The activity of superoxide dismutase (SOD) and level of malondialdehyde(MDA) were determined with spectrophotometer. The expression levels of Nrf2, GCLC, SOD2 and VDR in testis were detected by western blot.Results:At baseline, compared with NC group, testicular weight, serum testosterone level, SOD activity, Nrf2, GCLC and SOD2 expression levels were significantly decreased in DG group, while MDA level was significantly increased. After vitamin D supplementation, testicular weight, testosterone levels and SOD activity in both of HD and LD groups were significantly increased, while the MDA level was significantly decreased. The expression levels of Nrf2, GCLC, SOD2 and VDR were significantly increased.Conclusion:Vitamin D supplementation may enhance the testicular antioxidant capacity through activating Nrf2-ARE signaling pathway, and improve the testicular function in D-galactose-induced aging rats.

Objective:To investigate the correlation between the level of thyrotropin receptor antibody(TRAb) and bone turnover markers(BTMs) in the patients with newly-diagnosed Graves′ disease(GD).Methods:The clinical data of GD patients who were newly-diagnosed in the First Affiliated Hospital of Zhengzhou University from October 2016 to June 2021 were collected, including free triiodothyronine(FT 3), free thyroxine(FT 4), thyroid stimulating hormone, thyroid related antibodies, N-terminal procollagen of type I collagen(PINP), N-terminal osteocalcin(N-MID), β-cross-linked C-telopeptide of type I(β-CTX), blood lipid and renal function, etc. Results:There were 618 GD patients with an average age of(43.7±13.2) years(male∶female=1∶1.99). The PINP and β-CTX level in male GD patients were significantly higher than those in female(all P<0.05). Spearman correlation analysis showed that PINP, N-MID and β-CTX were positively correlated with FT 3, FT 4, TRAb, serum calcium and serum phosphorus; and negatively correlated with body mass index and low density lipoprotein cholesterol(all P<0.05). Linear regression analysis showed that TRAb was positively correlated with lg-PINP, lg-N-MID and sqrt-β-CTX in the univariate model of total GD patients( β were 0.006, 0.005, and 0.006, respectively; all P<0.001); positive correlation remained after adjusting for thyroid function(all β=0.004, all P<0.001); and for multiple confounding factors(model 3 and 4, all P<0.05). Results of univariate and adjusted thyroid function models with GD in different genders were consistent with the total patients(all P<0.05). Conclusion:TRAb is a risk factor for accelerated bone turnover in GD patients which is independent of thyroid function.

Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.

Objective:To compare the spermatogenes response of human chorionic gonadotropin(HCG)combined with human menopausal gonadotropin(HMG)in patients with idiopathic hypogonadotropic hypogonadism(IHH)and congenital combined pituitary hormone deficiency(CCPHD), and to explore related factors.Methods:Clinical data of 90 IHH patients and 61 CCPHD patients from January, 2014 to November, 2018 were retrospectively analyzed. Spermatogenesis was compared between the two groups receiving combined gonadotropin therapy. The patients were then divided into two subgroups: spermatogenesis subgroup and nonspermatogenesis subgroup. Related factors of spermatogenesis after the combined gonadotropin therapy were investigated.Results:After the combined treatment of HCG/HMG for 3, 6, and 9 months, the patients with CCPHD revealed lower testicular sizes than those with IHH( P=0.004, 0.021 and 0.032, respectively). Compared with IHH patients, CCPHD patients had larger testicular volume increments( P<0.001), higher spermatogenesis rates( P=0.048), and shorter initial time for sperm appearance( P<0.001)after 24-month treatment. Multivariate logistic regression analysis showed that lower total cholesterol(TC)(IHH group: OR=5.508, 95% CI 1.110-27.326, P=0.037; CCPHD group: OR=4.068, 95% CI 1.077-15.371, P=0.039)was an independent risk factor of poorer spermatogenesis in patients with IHH and CCPHD. Conclusions:The patients with CCPHD demonstrate a better response to combined gonadotropin treatment than those with IHH. Lower TC is an independent risk factor for poor spermatogenesis of combined HCG/HMG therapy in patients with IHH or CCPHD.

Objective:To summarize the clinical manifestations and molecular genetic characteristics of 5 families with maturity-onset diabetes mellitus of the young 2 (MODY2) caused by glucokinase (GCK) gene mutations.Methods:Clinical data and biochemical results of probands were collected. Peripheral blood samples of probands and first-degree family members were collected and whole exome gene was detected using second-generation sequencing. After comparing against the database, the suspected pathogenic sites were selected for Sanger sequencing verification.Results:All the 5 probands presented with mild fasting hyperglycemia, HbA 1C<7.5%, and no symptoms of thirst, polydipsia or polyuria. There were 6 mutants in 5 families, including M1: c.555delT (P.leu186CysFS Ter19) and M3: c. 263T>A (p.Met88Lys) which haven′t been reported before. During the follow-up, all probands received life-style intervention, except 2 pregnant women who should consider insulin treatment if necessary according to fetal genotypes. Conclusion:Among patients who meet the diagnostic criteria for MODY, MODY2 screening should be performed for children or pregnant women with mild hyperglycemia and family history. GCK gene detection is the gold standard for diagnosis, and accurate diagnosis will be conducive to the selection of appropriate treatment.

Objective:To investigate the efficacy and safety of radiotherapy for all metastases in patients with metachronous oligo-metastatic prostate cancer after radical treatment.Methods:From October 2011 to February 2021, 41 patients with prostate cancer with less than 5 metastases after radical treatment were retrospectively analyzed in a single center. The median age at radiotherapy was 68 (57-81) years. Forty patients (98%) received androgen deprivation therapy (ADT). There were 28 patients in the hormone sensitive (HSPC) group and 13 patients in the hormone resistant (CRPC) group. The median initial PSA was 24.4 (7.4-399.0) ng/ml. Tumor stage: T 2 stage 11 patients, T 3 stage 27 patients, T 4 stage 3 patients.30 patients were in N 0 stage and 11 patients in N 1 stage. Gleason score was 7 in 12 patients, 8 in 9 patients, 9 in 18 patients, and 10 in 2 patients.33 patients were treated with surgery, and 8 patients were treated with radiotherapy. The time span from diagnosis to metastasis was 3.1 (0.2-1.8) years. Conventional imaging examination (CT/ MRI/bone scan) before radiotherapy was used in 7 patients, and PSMA PET/CT examination was used in 34 patients.The median PSA before radiotherapy was 1.3(0.1-33.8) ng/ml. There were 62 metastases in 41 patients, including 1 lesion in 28 patients, 2 lesions in 9 patients, 3 lesions in 2 patients, and 5 lesions in 2 patients. Fifty-four patients had bone metastases and eight had retroperitoneal lymph node metastases. Twenty-two bone metastases were located in the pelvis, 18 in the vertebral body, 12 in the ribs, one in the femur and one in the sternum.The median metastatic volume was 5.8(0.2-81.7) cm 3.Daily image-guided rotational intensity modulated radiotherapy was used to cover all metastases.Dose segmentation modes include 37.5Gy/7.5Gy/5F, 60Gy/3Gy/20F, 65-70Gy/2.6-2.8Gy/25F.The median biological effective dose (BED 3) was 120 (67-147) Gy. The primary endpoint was biochemical progression-free survival (BPFS), the secondary endpoints were acute and late toxic side effects, local relapse-free survival (LPFS), and overall survival (OS). Results:The median follow-up time was 21 months (range 5-72 months). All patients completed radiotherapy, and 16 patients had grade 1 to 2 acute toxicity and side effects, and no grade 3 or above acute and late stage side effects. 1-year LPFS was 97.1%.The 1-year and 2-year BPFS were 77.5% and 59.2%, respectively. The median BPFS time was 29 months (range 13.9-44.2 months). Univariate analysis showed that the HSPC group ( P<0.001) and the group with total metastatic volume ≤ 5.8cm 3 ( P=0.010) had higher BPFS. The median BPFS time was 37 months in the retroperitoneal lymph node metastases subgroup and 17 months in the bone metastases subgroup ( P=0.141). In the HSPC group, the median BPFS was 30(22-38) months. After radiotherapy, PSA decreased in all 28 patients, and increased in 6 patients. The median BPFS was 12(4-18) months. In the CRPC group, the median BPFS was 4(0-8) months. PSA decreased in 10 patients (76.9%) after radiotherapy, and PSA decreased in 6 patients. The median BPFS was 5(3-28) months. Three patients’PSA did not decrease after radiotherapy, and they were treated with new endocrine therapy drugs, chemotherapy, immunotherapy and other systemic therapy. Conclusions:For patients with metachronous metastases after radical treatment, full coverage radiotherapy has good safety and high local control rate. HSPC patients and patients with low tumor load could be recommended to receive radiotherapy for all metastatic lesions preferentially, and patients with only retroperitoneal lymph node metastases may have better prognosis after radiotherapy than patients with bone metastases.

In recent years, the incidence of diabetic kidney disease(DKD) has been increasing gradually, and it has become the leading cause of end-stage renal disease. However, current therapies show limited efficacy in preventing the progression of DKD. Against the backdrop of chip and high-throughput sequencing, long non-coding RNAs are revealed to an important role in the pathogenesis of DKD. This article summarizes the research progress of long non-coding RNA in DKD, and look forward to the more extensive application of long non-coding RNA in the future.