ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

ObjectiveTo investigate the protective effects and mechanisms of Zhenzhu Tiaozhi capsules on the kidneys in the mouse model of diabetic kidney disease. MethodsThirty male C57BL/6J mice were selected as experimental objects. The model of diabetic kidney disease was induced by intraperitoneal injection of streptozotocin （STZ） at 40 mg·kg^-1 for 5 days combined with a high-fat diet （HFD）. Fasting blood glucose （FBG） ≥ 11.1 mmol·L^-1， increased urine volume， and continuous appearance of proteinuria indicated successful modeling. Mice were grouped as follows： Blank， model， low- and high-dose （0.98 and 1.96 g·kg^-1， respectively） Zhenzhu Tiaozhi capsules， and losartan potassium （30 mg·kg^-1）， with six mice in each group. After 12 weeks of continuous gavage， urine and kidney specimens were collected， and the 24-h urinary protein and the urinary albumin-to-creatinine ratio （UACR） in mice were measured. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining were performed for observation of histopathological changes in kidneys. Immunofluorescence assay was employed to detect the positive expression of the podocyte marker protein nephrin. Oil red O staining was used to detect renal lipid deposition. Enzyme linked immunosorbent assay was employed to measure the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the renal tissue. Western blot was employed to determine the expression levels of sterol regulatory element-binding protein cleavage-activating protein （SCAP）， sterol regulatory element-binding protein-1c （SREBP-1c）， and NOD-like receptor protein 3 （NLRP3） in the renal tissue. ResultsCompared with the blank group， the model group showed increases in 24-h urinary protein and UACR （P<0.05）， glomeruli exhibiting capsule adhesion， collagen fiber deposition， mesangial proliferation， and inflammatory cell infiltration， elevated levels of IL-1β， IL-6， and TNF-α （P<0.05）， reduced positive expression of nephrin （P<0.05）， increased lipid deposition （P<0.05）， and up-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. Compared with the model group， the treatment with losartan potassium or high-dose Zhenzhu Tiaozhi capsules for 12 weeks decreased 24-h urinary protein and UACR （P<0.05）， and the treatment with low-dose Zhenzhu Tiaozhi capsules for 12 weeks reduced the 24-h urinary protein （P<0.05）. Pathological staining results revealed that kidney damage in mice from all treatment groups was alleviated， with reduced inflammatory infiltration， collagen fiber deposition， and mesangial proliferation， and increased positive expression of nephrin in the renal tissue （P<0.05）. In addition， all the treatment groups showed reduced lipid droplets （P<0.05）， lowered levels of IL-1β， IL-6， and TNF-α （P<0.05）， and down-regulated expression of SCAP， SREBP-1c， and NLRP3 （P<0.05） in the renal tissue. ConclusionZhenzhu Tiaozhi capsules can ameliorate kidney damage in the mouse model of diabetic kidney disease by inhibiting the activation of the SCAP-SREBP-1c/NLRP3 signaling pathway， which reduces renal lipid deposition and inflammation.

Objective:To investigate the lipidomics differences of CD4+T immune cells in diabetic kidney disease(DKD)mice,and screen out the differential metabolites with biological significance.Methods:CD4(L3T4)MicroBeads immunomagnetic beads were used to isolate CD4+T immune cells from spleen of BKS.Cg-Dock7m+/+Leprdb/J mice with spontaneous DKD;the purity of CD4+T cells were identified by flow cytometry.The non-targeted lipidomics of CD4+T cells were detected by LC-MS/MS,and the differ-ential metabolites were analyzed.Results:A total of 463 metabolites were detected by LC-MS.PCA and OPLS-DA analysis showed that the metabolic components were significantly separated;twenty-four differential metabolites were screened out.KEGG and enrich-ment analysis showed that the differential metabolites involved in the disorder of glycerol phospholipid metabolism.Conclusion:Phos-pholipid metabolism of CD4+T cells is closely related to the occurrence of DKD.Phospholipid metabolism targeting DKD CD4+T cells in DKD may be a new direction of DKD treatment.

Objective:To test the validity and reliability of the Chinese version of the Pre-sleep Arousal Scale(PSAS)in patients with brief insomnia disorder(BID).Methods:Totally 170 patients with BID and 150 normal sleepers(NS)were recruited.All participants were assessed with the PSAS,Hospital Anxiety and Depression Scale(HADS)and Insomnia Severity Index(ISI).After 3 months,72 patients with BID were retested with the PSAS,HADS and ISI.Results:The PSAS scores of BID group were characteristic of a normal distribution.The PSAS total scores were positively correlated with the scores of HADS and ISI(r=0.55,0.40,Ps＜0.01).Two factors of so-matic and cognitive arousal were extracted in PSAS by the exploratory factor analysis and parallel analysis,interval variance value was 55.84％,and the load scores of items were 0.46-0.89.The scores of PSAS and its subscales were higher in the BID group than in the NS group(Ps＜0.001).The best cut-off score for the overall PSAS was found at 32/33 and had high sensitivity(0.72)and specificity(0.81).The Cronbach's α coefficient and the Spearman Brown split reliability were 0.91 and 0.76,respectively,the correlation coefficients between the items and total score ranged from 0.46 to 0.89(Ps＜0.01),and the test-retest reliability was 0.37(P＜0.01).Addi-tionally,rate of change of PSAS scores was positively correlated with the rate of change of HADS scores and ISI scores(Ps＜0.05).Conclusion:The Chinese version of PSAS is a reliable and valid instrument to assess pre-sleep arousal in patients with brief insomnia disorder.

Objective To explore the safety and mid-term efficacy of autologous hamstring tendon implantation in the treatment of severe anterior vaginal wall prolapse.Methods We performed a prospective single arm clinical study.From May 2021,pelvic organ prolapse(POP)patients with severe anterior vaginal wall prolapse as the main cause who had symptoms and required surgical treatment were included.The patient was fully informed and voluntarily selected autologous hamstring tendon implantation and high sacral ligament suspension.Postoperative follow-ups were carried out on the Pelvic Organ Prolapse Quantification(POP-Q),Pelvic Floor Distress Inventory-Short Form 20(PFDI-20),postoperative satisfaction score,and Patient Global Impression of Improvement(PGI-I).Function of the lower limb on the tendon removal side,as well as postoperative complications and re-operations were recorded.Results The operation time of tendon removal was(19.7±8.3)min,the operation time of pelvic floor was(122.1±37.8)min,the median intraoperative bleeding volume was 70 ml(range,50-400 ml),and there was no intraoperative co-morbidity or postoperative fever.A total of 12 cases were followed up for(26.4±2.5)months.The measured values of Aa,Ba,and C were 3(-1-3),5(2-10),and 4(-1-10)before operation and-3(-3-3),-3(-3-3),and-6(-6-3)at 24 months after operation,respectively,with significant difference(P＜0.05).The PFDI-20 scores of the 12 patients before surgery and at 24 months after surgery were 88.0 points(range,16.7-204.2 points)and 8.3 points(range,0-32.3 points),respectively,with significant difference(Z=-2.803,P=0.005).The PGI-I questionnaire showed 11 patients with significant improvement in postoperative symptoms and 1 patient with improvement.The satisfaction scores at 6 and 24 months after surgery were(4.8±0.4)points and(4.6±0.7)points,respectively.One patient experienced vaginal prolapse at 12 months after surgery,with a Ⅲ degree prolapse of the anterior wall and vaginal vault,the recurrence rate being 8.3％(1/12).Two patients had pulmonary embolism at 9 d and 2 weeks after surgery,with Clavien-Dindo Ⅱ and Ⅲ grades,and recovered after outpatient and hospitalization treatment.One patient was found fascia exposure at the vagina,and had improvement with medication treatment.All the patients had good wound healing at the tendon removal site,with normal muscle strength and lower limb activity.No re-operation was required due to recurrence or complications of tendon surgery.Conclusions Autologous hamstring tendon implantation is safe in the treatment of severe anterior vaginal wall prolapse with satisfactory mid-term efficacy.Before surgery,it is necessary to educate patients on lower limb exercise to prevent complications of venous thrombosis.

Methods: From May 2021 to August 2021, panelists were chosen to collect expert feedback using the modified Delphi method, and 74 spine surgeons from across China agreed to participate. Four rounds were conducted: one in-person meeting and three subsequent survey rounds. Each question received at least 70.0% agreement, indicating a consensus. The grade A, B, and C recommendation were defined as having ≥90.0%, 80.0%–89.9%, and 70.0%–79.9% agreement on each question, respectively. Results: The panelist group consisted of 74 experts, and 72, 70, and 69 questionnaires were collected in three rounds, respectively. In total, 24 questions with 59 options reached consensus after the Delphi rounds, including indications (adjacent vertebral diseases after lumbar internal fixation) and contraindications (previous surgery or bone destructive diseases lead to the destruction or absence of bone in the lamina or isthmus); advantages (intraoperative traction of paravertebral soft tissue is small) and disadvantages (not three-column fixation.); preoperative evaluation; complications; and postoperative follow-up evaluation, of CBT. Conclusions The modified Delphi method achieved expert consensus on the clinical use of CBT for lumbar pedicle screws. This consensus document establishes clear guidelines for indications, contraindications, surgical techniques, and postoperative management, thereby enhancing clinical decision-making and promoting the safe and effective use of CBT. While the initial study focused on Chinese surgeons, future research will seek to validate and expand these findings from a broader international perspective.

OBJECTIVE: To investigate the clinical value of analgesia and sedation under bispectral index (BIS) monitoring combined with hydraulic coupled intracranial pressure (ICP) monitoring in severe craniocerebral injury (sTBI). METHODS: (1) A prospective self-controlled parallel control study was conducted. A total of 32 patients with sTBI after craniotomy admitted to the intensive care unit (ICU) of the First People's Hospital of Huzhou from December 2020 to July 2021 were selected as the research objects. ICP was monitored by Codman monitoring system and hydraulically coupled monitoring system, and the difference and correlation between them were compared. (2) A prospective randomized controlled study was conducted. A total of 108 sTBI patients admitted to the ICU of the First People's Hospital of Huzhou from August 2021 to August 2022 were selected patients were divided into 3 groups according to the random number table method. All patients were given routine treatment after brain surgery. On this basis, the ICP values of the patients in group A (35 cases) were monitored by Codman monitoring system, the ICP values of the patients in group B (40 cases) were monitored by hydraulic coupling monitoring system, and the ICP values of the patients in group C (33 cases) were monitored combined with hydraulic coupling monitoring system, and the analgesia and sedation were guided by BIS. The ICP after treatment, cerebrospinal fluid drainage time, ICP monitoring time, ICU stay time, complications and Glasgow outcome score (GOS) at 6 months after surgery were compared among the 3 groups. In addition, patients in group B and group C were further grouped according to the waveforms. If P₁ = P₂ wave or P₂ and P₃ wave were low, they were classified as compensatory group. If the round wave or P₂ > P₁ wave was defined as decompensated group, the GOS scores of the two groups at 6 months after operation were compared. RESULTS: (1) There was no significant difference in ICP values measured by Codman monitoring system and hydraulic coupling monitoring system in the same patient (mmHg: 11.94±1.76 vs. 11.88±1.90, t = 0.150, P = 0.882; 1 mmHg≈0.133 kPa). Blan-altman analysis showed that the 95% consistency limit (95%LoA) of ICP values measured by the two methods was -4.55 to 4.68 mmHg, and all points fell within 95%LoA, indicating that the two methods had a good correlation. (2) There were no significant differences in cerebrospinal fluid drainage time, ICP monitoring time, ICU stay time, and incidence of complications such as intracranial infection, intracranial rebleeding, traumatic hydrocephalus, cerebrospinal fluid leakage, and accidental extubation among the 3 groups of sTBI patients (P > 0.05 or P > 0.017). The ICP value of group C after treatment was significantly lower than that of group A and group B (mmHg: 20.94±2.37 vs. 25.86±3.15, 26.40±3.09, all P < 0.05), the incidence of pulmonary infection (9.1% vs. 45.7%, 42.5%), seizure (3.0% vs. 31.4%, 30.0%), reoperation (3.0% vs. 31.4%, 40.0%), and poor prognosis 6 months after operation (33.3% vs. 65.7%, 65.0%) were significantly lower than those in group A and group B (all P < 0.017). According to the hydraulic coupling waveform, GOS scores of 35 patients in the compensated group were significantly higher than those of 38 patients in the decompensated group 6 months after operation (4.03±1.18 vs. 2.39±1.50, t = 5.153, P < 0.001). CONCLUSIONS The hydraulic coupled intracranial pressure monitoring system has good accuracy and consistency in measuring ICP value, and it can better display ICP waveform changes than the traditional ICP monitoring method, and has better prediction value for prognosis evaluation, which can replace Codman monitoring to accurately guide clinical work. In addition, analgesia and sedation under BIS monitoring combined with hydraulic coupled ICP monitoring can effectively reduce ICP, reduce the incidence of complications, and improve the prognosis, which has high clinical application value.
Humans ; Intracranial Pressure ; Prospective Studies ; Monitoring, Physiologic/methods* ; Craniocerebral Trauma ; Analgesia ; Cerebrospinal Fluid Leak

COVID-19 pandemic has put a huge burden on public health and global economy. Vaccines play an important role in controlling virus transmission and reducing mortality. While monoclonal virus neutralizing antibodies can reduce the viral load, improve symptoms, and prevent the aggravation of the disease from hospitalization. Now hundreds of clinical trials of COVID-19 vaccine and monoclonal neutralizing antibody are in progress. The vaccine focuses on disease prevention, while the neutralizing antibody focuses on disease treatment. There are quite many differences between the two kinds of clinical trials by following different technical guidelines, research purpose, trial design, implementation and outcome assessment. Therefore, it is necessary to summarize the similarities and differences between the clinical trials for the reference of new drug research and development as well as clinical researchers.

Objective:To investigate the clinical value of zoledronic acid in improving the prognosis of osteoporotic hip fracture and preventing its sequential contralateral hip fracture.Methods:A retrospective study of 206 patients diagnosed with hip fragile fractures in China Medical University Affiliated Shengjing Hospital and treated with anti-osteoporotic drugs after surgery was conducted. The prognosis of patients with hip fracture using survival rate analysis and the risk factors of acute febrile complications with multivariate analysis after zoledronic acid treatment were evaluated. Furthermore, chi-square test and multivariate analysis was used to explore whether zoledronic acid decreases the occurrence of the contralateral sequential fracture.Results:The 3-year survival rate of patients with overall hip fracture was higher in zoledronic acid treatment group compared with control group( P=0.026), with the incidence of fever at 53.3%. The age [ OR=0.786, P=0.027, the area under receiver operating characteristic (ROC) curve was 0.724] and cardiopulmonary complications ( OR=0.043, P=0.025, the area under ROC curve was 0.628) were significantly correlated with the occurrence of acute febrile response. The incidence of sequential contralateral fractures in zoledronic acid treatment group was significantly lower than that in control group ( χ2=4.356, P=0.037). The application of zoledronic acid ( OR=0.160, P=0.007, the area under ROC curve is 0.586) and the type of femoral neck fracture ( OR=0.196, P=0.001, the area under ROC curve is 0.607) were statistically associated with the occurrence of sequential fractures. Conclusion:Zoledronic acid treatment improves the outcome of patients with osteoporotic hip fracture and reduces the incidence of sequential hip fractures, especially femoral neck fracture. Senile age and cardiopulmonary complications might be associated with lower risk of acute febrile reactions after zoledronic acid treatment.

Objective:To explore the efficacy and safety of Ganhai Weikang capsule (GWC) in the treatment of functional dyspepsia (FD).Methods:A randomized, double-blind, placebo-controlled parallel, multi-center, superiority clinical trial was conducted. From March 2018 to April 2020, totally 324 patients with dyspepsia symptoms, who were diagnosed as chronic non-atrophic gastritis by endoscopy and pathology and met the Rome Ⅳ diagnostic criteria for FD from 7 top hospitals were enrolled, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Heilongjiang Hospital of Traditional Chinese Medicine, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Qilu Hospital of Shandong University, the First Affiliated Hospital of Zhejiang University, Beijing Hospital of Traditional Chinese Medicine of Capital Medical University and the Third Xiangya Hospital of Central South University. The patients were randomly divided into the GWC group and the placebo group according to the ratio of 1∶1. The patients of GWC group were given GWC and the patients of placebo group were given GWC capsule simulant. The patients of both groups orally took capsules before meals, 2.4 g each time and 3 times per day, and the course of treatment was 4 weeks. The main efficacy index was the total clinical effective rate after 4 weeks, and the secondary efficacy index was the changes of clinical symptom scores of upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety. The safety index included laboratory tests and adverse events. Chi-square test and Wilcoxon rank sum test were used for statistical analysis.Results:A total of 320 FD patients were enrolled in the full analysis set (FAS), which included 161 cases in GWC group and 159 cases in placebo group. A total of 298 cases were in the per-protocol set (PPS), 149 cases each in GWC group and placebo group. The results of FAS and PPS both showed that the total clinical effective rates of the GWC group were higher than those of the placebo group (84.5%, 136/161 vs. 44.0%, 70/159 and 83.9%, 125/149 vs. 46.3%, 69/149), and the differences were statistically significant ( χ2=57.07 and 46.32, both P<0.001). In addition, the differences of the total score of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (FAS: 10 (7, 14) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 3); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs. 1 (0, 3). PPS: 10 (7, 13) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 2); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs.1 (0, 3)), and the differences were statistically significant (FAS: Z=5.80, 5.91, 3.19, 3.72 and 3.30; PPS: Z=5.14, 5.11, 2.86, 3.21 and 2.84; all P<0.01). The results of FAS and PPS indicated that the improvement rates of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) of GWC group were all higher than those of the placebo group (FAS: 77.8% (54.6%, 91.3%) vs. 42.9% (28.6%, 61.5%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 60.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 41.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%). PPS: 77.8% (54.2%, 89.5%) vs. 44.0% (28.6%, 65.0%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 46.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%)), and the differences were statistically significant (FAS: Z=8.60, 7.72, 4.98, 4.24 and 5.61; PPS: Z=7.90, 7.03, 4.49, 3.88 and 4.83; all P<0.001). After 2 weeks of treatment, the differences of the total score of main symptoms and score of each symptom (upper abdominal pain, upper abdominal burning and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (5.0 (3.0, 8.0) vs. 4.0 (2.0, 6.0); 2.0 (1.0, 2.0) vs. 2.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0)), and the differences were statistically significant ( Z=2.95, 3.44, 2.43 and 2.79, all P<0.05). There was no significant difference in the incidence of adverse events between the GWC group and the placebo group (0.6%, 1/163 vs. 0, 0/159). Conclusion:The clinical total effective rate of GWC in the treatment of FD is superior to that of placebo and it has good safety.