Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Acute pancreatitis （AP） is a common clinical acute abdominal disease， which is characterized by acute onset， rapid development， severe disease， many complications， and high mortality rate. It can progress to severe AP （SAP） if not treated promptly in the early stage. The pathogenesis of AP is complex and involves multiple cellular and molecular levels. It is now clear that oxidative stress and reactive oxygen species （ROS） production are involved in the physiopathological process of AP， which is associated with a low quantity and activity of antioxidant enzymes in pancreatic cells. Nuclear factor E₂-related factor 2 （Nrf2） serves as the ''golden key'' to maintain redox homeostasis in tissue cells and constitutes an important signaling pathway for antioxidant response and inflammation in vivo by collaborating with downstream antioxidant enzymes such as heme oxygenase-1 （HO-1）. Traditional Chinese medicine has unique efficacy in treating diseases due to its multi-component， multi-target， multi-drug delivery， and multi-formulation characteristics. Based on the concept of synergy between traditional Chinese and Western medicine， traditional Chinese medicine is becoming a new craze in the treatment of AP. The level of oxidative stress and Nrf2/HO-1 signaling pathway in AP pancreatic tissue are in a dynamic change process， and the intervention of traditional Chinese medicine can clean ROS production， affect the inflammatory pathway， and reduce oxidative stress damage， so as to protect against pancreatic injury. This suggests that this pathway plays an important role in AP. This article reviews the recent literature on the regulation of the Nrf2/HO-1 signaling pathway by traditional Chinese medicine for AP and summarizes that the monomers of traditional Chinese medicine targeting this pathway are mainly heat-clearing and detoxifying， blood-activating and blood-stasis-removing， and Qi benefiting and middle warming， and the compounds of traditional Chinese medicine include Yinchenhao Decoction and QingYi Ⅱ， so as to provide a new direction for the prevention and treatment of AP and further drug development.

ObjectiveTo investigate the therapeutic effect of Qingjie Huagong decoction （QJHGD） on a mouse model of severe acute pancreatitis （SAP） and the mechanism of action of QJHGD against inflammatory response. MethodsA total of 36 male C57BL/6J mice were randomly divided into blank group， model group， Western medicine group （ulinastatin）， and low-， middle-， and high-dose QJHGD groups， with 6 mice in each group. All mice except those in the blank group were given 5% sodium taurocholate by retrograde pancreaticobiliary injection to establish a model of SAP. After modeling， the mice in the low-， middle-， and high-dose groups were given QJHGD （1， 2， and 4 g/kg， respectively） by gavage， and those in the Western medicine group were given intraperitoneal injection of ulinastatin （5×10⁴ U/kg）， for 7 days in total. HE staining was used to observe the histopathological changes of the pancreas； ELISA was used to measure the levels of α-amylase， lipase， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α） in mice； RT-qPCR was used to measure the mRNA expression levels of NOD-like receptor protein3 （NLRP3）， Toll-like receptor 4 （TLR4）， and nuclear factor-kappa B （NF-κB） in pancreatic tissue； immunohistochemistry was used to measure the positive expression rates of NLRP3， TLR4， and NF-κB in pancreatic tissue； Western blot was used to measure the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6. An 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 blank group， the model group had diffuse destruction of pancreatic tissue structure， focal dilatation of pancreatic lobular septum， pancreatic acinar atrophy， and massive inflammatory cell infiltration， as well as significant increases in the content of α-amylase， lipase， IL-1β， IL-6， IL-8， IL-18， and TNF-α （all P<0.05）， the mRNA expression levels and positive expression rates of NLRP3， TLR4， and NF-κB （all P<0.05）， and the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6 （all P<0.05）. Compared with the model group， the low-， middle-， and high-dose QJHGD groups and the Western medicine group had slightly tighter and more intact structure of pancreatic tissue， ordered arrangement of pancreatic acinar cells， a small amount of inflammatory cell infiltration， and hemorrhagic foci of pancreatic lobules， as well as significant reductions in the content of α-amylase， lipase， IL-1β， IL-6， IL-8， IL-18， and TNF-α （all P<0.05）， the mRNA expression levels and positive expression rates of NLRP3， TLR4， and NF-κB （all P<0.05）， and the protein expression levels of NLRP3， TLR4， NF-κB， IL-1β， and IL-6 （all P<0.05）. ConclusionQJHGD may exert a protective effect on the pancreatic tissue of SAP mice by inhibiting the activation of NLRP3/TLR4/NF-κB signaling pathway-related proteins， reducing the release of inflammatory mediators， and preventing the enhancement of inflammatory cascade response.

Objective:To explore the application value of ultrasound diaphragmatic function assessment in weaning from invasive mechanical ventilation in patients with respiratory failure.Method:Fifty-three patients with acute respiratory failure who underwent mechanical ventilation and weaning in People’s Hospital Affiliated to Ningbo University from January 2020 to February 2022 were selected for research. After weaning conditions, T-tube was used for spontaneous breathing test (SBT). At SBT-30 min, beside ultrasound was used to collect the right diaphragm movement (DE) and diaphragm thickness, and the shallow rapid breathing index (RSBI), diaphragm shallow rapid breathing index (D-RSBI) and diaphragm thickness change rate (DTF) were calculated. According to the outcome of weaning, the patients were divided into the successfully weaned group and unsuccessfully weaned group. All patients’ clinical data were collected, and the relationship between ultrasound parameters and clinical indexes was compared between the two groups The efficiency of each index for predicting the success rate of weaning was analyzed with the receiver operating characteristic (ROC) curve.Results:Fifty-three patients were enrolled in this study, including 36 patients in the successfully weaned group and 17 patients in the unsuccessfully weaned group. DE and DTF in the successfully weaned group were higher than those in the unsuccessfully weaned group (all P<0.05), RSBI and D-RSBI in the successfully weaned group were significantly lower than those in the unsuccessfully weaned group (all P<0.05). ROC curve analysis showed that when the cut-off value of DE, DTF, RSBI and D-RSBI were >1.21 cm, >27.5%, <48.68 times/(min·L) and <1.31 times/(min·mm), the sensitivity of predicting the success of weaning was 69.0%, 97.2%, 83.0% and 83.0% respectively, and the specificity was 59.0%, 47.1%, 94.1% and 94.3%, respectively. Conclusions:The evaluation of ultrasound diaphragmatic function can effectively guide the clinical mechanical ventilation patients to withdraw the machine, and improve the accuracy of predicting the success rate of weaning. Therefore, t ultrasound diaphragmatic function assessment has a high application value in guiding the mechanical evacuation of patients with mechanical ventilation, and can be widely applied in clinical practice.

Objective:To investigate the feasibility and effectiveness of incision subcutaneous porous catheter combined with ropivacaine analgesia in enhanced recovery after laparoscopic gastrointestinal surgery.Methods:The clinical data of 140 patients underwent gastrointestinal surgery from August 2021 to April 2022 in Shanghai Fourth People′s Hospital, School of Medicine, Tongji University were retrospectively analyzed. Among them, 70 patients were given routine postoperative analgesia (control group), and 70 patients were given incision subcutaneous porous catheter combined with ropivacaine analgesia on the basis of routine postoperative analgesia (observation group). The visual analogue score (VAS) 4, 24, 32, 48, 56 and 72 h after operation was evaluated; and the complications of subcutaneous catheterization, incision infection, postoperative nausea vomiting, neurological symptoms, time to extubation, patient satisfaction degree, recovery time of intestinal function and hospital stay were recorded.Results:The VAS 4, 24, 32, 48, 56 and 72 h after operation in observation group was significantly lower than that in control group: 1.000 (- 0.250, 2.250) scores vs. 1.000 (- 1.000, 3.000) scores, 2.000 (1.000, 3.000) scores vs. 4.000 (2.000, 6.000) scores, 1.000 (0.000, 2.000) scores vs. 3.000 (1.000, 5.000) scores, 2.000 (1.000, 3.000) scores vs. 3.000 (1.750, 4.250) scores, (1.100 ± 0.934) scores vs. (2.085 ± 0.943) scores and (0.985 ± 0.842) scores vs. (1.814 ± 0.921) scores, and there was statistical difference ( P<0.05 or <0.01). The recovery time of intestinal function and hospital stay in observation group were significantly shorter than that that in control group: (1.743 ± 0.557) d vs. (2.200 ± 0.714) d and (8.043 ± 1.160) d vs. (8.757 ± 1.221) d, and there were statistical difference ( P<0.01); there were no statistical differences in the rate of incision infection, incidence of postoperative nausea vomiting, time to extubation and patient dissatisfaction rate between two groups ( P>0.05); there were no the complications of subcutaneous catheterization and neurological symptoms in two groups. Conclusions:The incision subcutaneous porous catheter combined with ropivacaine analgesia after laparoscopic gastrointestinal surgery is a safe, effective and feasible method. Multimodal analgesia under enhanced recovery after surgery can increase the postoperative recovery after gastrointestinal operations and shorten the postoperative hospital stay.

The multi-campus mode is an important way to give full play to the advantages of public hospitals and promote the expansion of high-quality medical resources and balanced regional layout. The authors summarized the practical experience of the Second Affiliated Hospital Zhejiang University School of Medicine in promoting multi-campus cultural integration, including vertical dimensional initiatives including raising cultural construction to a strategic level, improving the working mechanism of cultural construction, and building a distinctive cultural identity system; horizontal dimensional initiatives including creating equal status and intergroup cooperation conducive to cultural integration, building a variety of forms of the main cultural communication platform, and building a unified and diverse cross-campus communication bridge. Through cultural integration, the internal cohesion of the hospital was enhanced and the influence of the hospital brand was improved. The authors suggested that cultural integration should always be based on the principle of " seeking common ground while preserving minor differences" , focusing on the construction of systems and standards, and focusing on the construction of communication platforms.

Objective:To investigate the clinical predictive value of combined diaphragmatic and pulmonary ultrasound in acute respiratory failure patients with mechanical ventilation (MV).Methods:From January 2020 to August 2022, patients with acute respiratory failure admitted to People's Hospital Affiliated to Ningbo University who underwent invasive MV and weaning were enrolled. After meeting the weaning standards, spontaneous breathing test (SBT) was performed using T-tube. Right diaphragm excursion (DE), diaphragm thickness and lung ultrasound score (LUS) were collected by bedside ultrasound at 30 minutes of SBT, and rapid shallow respiratory index (RSBI), diaphragmatic-shallow respiratory index (D-RSBI) and diaphragmatic thickening rate (DTF) were calculated. According to the weaning outcome, the patients were divided into successful weaning group and failed weaning group. The clinical data of all patients were collected, and the ultrasound parameters and clinical indicators were compared between the two groups. Receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of D-RSBI, RSBI, DE combined with LUS score and DTF combined with LUS score for weaning failure patients.Results:A total of 77 patients were enrolled, including 54 cases in the successful weaning group and 23 cases in the failed weaning group. The right DE and DTF of patients in successful weaning group were significantly higher than those in failed weaning group [right DE (cm): 1.28±0.39 vs. 0.88±0.41, DTF: (32.64±18.27)% vs. (26.43±15.23)%, both P < 0.05], LUS score, RSBI and D-RSBI were significantly lower than those in failed weaning group [LUS score: 11.45±2.67 vs. 18.33±3.62, RSBI (times·min -1·L -1): 72.21±19.67 vs. 107.35±21.32, D-RSBI (times·min -1·mm -1): 0.97±0.19 vs. 1.78±0.59, all P < 0.05]. ROC curve analysis showed that when the cut-off value of D-RSBI and RSBI was 1.41 times·min -1·mm -1 and 56.46 times·min -1·L -1, the area under the ROC curve (AUC) for predicting weaning failure was 0.972 and 0.988; and the sensitivity was 95.7% and 87.0%, respectively; the specificity was 81.0% and 100.0%, respectively. The AUC of right DE combined with LUS score and DTF combined with LUS score in predicting weaning failure were 0.974 and 0.985, respectively, with a sensitivity of 91.3% and a specificity of 98.1%. Conclusions:Combined assessment of diaphragmatic and pulmonary ultrasound is a good parameter to effectively predict weaning failure in MV patients, which has high application value in guiding weaning in MV patients, and is worthy of clinical application.

Objective:To investigate the effects of supplemental parenteral nutrition on postoperative nutritional status, immune function and inflammatory response in patients with esophageal cancer after operation.Methods:A prospective study was performed on 72 patients with esophageal cancer who visited the Department of Thoracic and Cardiovascular Surgery of the Affiliated Hospital of Putian University from June 2018 to June 2020. According to the random table of new drug data statistics and processing software, they were randomly divided into experimental group (supplementary parenteral nutrition group) and the control group (complete enteral nutrition group), with 36 cases in each group. The experimental group was given enteral nutrition (EN) from the first day after operation, and EN and parenteral nutrition (PN) was given on the 4th to 8th day after operation. In the control group, EN was started on the first day after operation. The changes of nutritional status, immune function and inflammatory indexes in the perioperative period were compared between the two groups. Mann-Whitney U test was used for measurement data that did not meet the normality standard, and t test was used to compare measurement data that met the normality standard between groups. Nutrition indicators, inflammatory indicators and immune indicators used repeated measures analysis of variance. For enumeration data, Mann-Whitney U test was used for hierarchical classification data, and χ 2 test was used for unordered multi-classification data. Results:On the 1st day after operation, the prealbumin concentration ((95.34±37.93) mg/L and (81.60±37.68) mg/L) in the experimental group and the control group was significantly higher than that before the operation ((144.86±46.79) mg/L and (130.39±50.91) mg/L), and the differences were statistically significant (all P<0.001), and there was no significant difference between the two groups (all P>0.05). Immunoglobulin (Ig) A ((0.48±0.39) g/L and (0.41±0.30) g/L), IgG ((4.21±3.44) g/L and (4.08±2.98) g/L), IgM( (0.32±0.26) g/L and (0.30±0.27) g/L) in the experimental group and the control group were compared with preoperative ((0.55±0.45) g/L and (0.47±0.39) g/L, (5.16±3.36) g/L and (5.48±3.30) g/L, (0.38±0.32) g/L and (0.35±0.30) g/L), and the difference was not statistically significant (all P>0.05), and there was no significant difference between the two groups (all P>0.05). In the experimental group and the control group, CD3 ((31.75±11.81) % and (28.03±9.30)%) were lower than those before operation ((40.86±12.50)% and (42.31±8.09)%), CD4 ((14.19±5.39)% and (16.06±9.08)%) were lower than those before operation ((21.69±8.54)% and (24.11±12.09)%), CD4/CD8 ((0.24±0.09) and (0.29±0.18)) were lower than those before operation ((0.42±0.16) and (0.50±0.28)), and CD8 ((59.03±8.14)% and (56.39±7.42)%) were lower than those before operation ((51.25±6.64)% and (49.14±6.53)%), the differences were statistically significant (all P<0.05). There was no significant difference in C3, C4 and C reactive protein (CRP) compared with preoperatively (all P>0.05), and there was no significant difference between the two groups (all P>0.05). On the 7th day after operation, the prealbumin concentration ((186.70±40.88) mg/L) in the experimental group was higher than that before operation and on the 1st day after operation, and the difference was statistically significant (all P<0.05), which was higher than that in the control group ((131.62±53.37) mg/L), the difference was statistically significant (all P<0.05); the prealbumin concentration in the control group ((131.62±53.37) mg/L) was higher than that on the 1st day after operation, and the difference was statistically significant (all P<0.05). IgA ((0.88±0.42) g/L), IgG ((10.70±4.39) g/L) in the experimental group was higher than that before operation, and the difference was statistically significant (all P<0.05), and it was higher than that on the 1st day after operation, and the difference was statistically significant (all P<0.05), lower than those in the control group ((0.59±0.44) g/L and (4.08±2.98) g/L), the difference was statistically significant (all P<0.05). In the test group, CD3 ((45.92±14.31)%), CD4 ((27.06±10.53)%), CD4/CD8 (0.66±0.33) increased and and CD8 (43.64±11.34%) decreased compared with the first day after operation, with statistically significant differences (all P<0.05). The elevated levels of CD4 and CD4/CD8 were statistically significant compared with the control group (all P<0.05). The CRP ((8.90±7.56) mg/L) in the experimental group on the 7th postoperative day was lower than that before operation and on the 1st postoperative day, and the difference was statistically significant (all P<0.05), which was lower than the control group ((16.24±13.53) mg/L), the difference was statistically significant (all P<0.05). The incidence of postoperative pulmonary infection (22.22% (8/36)), the incidence of anastomotic leakage (5.56% (2/36)), and the postoperative hospital stay ((14.17±4.79) d) in the experimental group were lower than those in the control group (44.44% (16/36), 25.00% (9/36), (18.47±6.34) d), the total hospitalization expenses in the experimental group ((71 261.94±11 503.50) yuan) were higher than those in the control group ((65 226.81±10 106.43) yuan), the difference was statistically significant (the statistical values were χ 2=4.00, χ 2=5.26, t=3.74, t=2.37; P values were 0.046, 0.022, <0.001 and 0.021, respectively). Conclusion:Supplemental parenteral nutrition for perioperative esophageal cancer patients can effectively maintain nutritional status, improve immune function, and reduce the inflammatory stress response.

Objective:To evaluate the clinical efficacy of TCM Qingjie Huagong Decoction combined with routine internal medicine in the treatment of severe acute pancreatitis with cholelithiasis (bile duct stones) in the early stage.Methods:Thirty-two patients with severe acute pancreatitis combined with cholelithiasis in the first affiliated Hospital of GuangXi University of Traditional Chinese Medicine were selected and randomly divided into two groups with 16 in each, both groups were treated for 14 days. Serum amylase (AMS) was detected by iodine-starch colorimetry, GOT and GPT were detected by continuous monitoring method, and CRP, IL-6 and procalcitonin (PCT) were detected by immune transmission turbidimetry. Acute Physiological and Chronic Health Score Ⅱ (APACHE Ⅱ), CT Severity Index Score (CTSI) and Modified Marshall Score were used to evaluate the severity of SAP. The recovery time of body temperature, the relief time of abdominal distension pain, the recovery time of bowel sounds and the total hospital stay were observed and recorded to evaluate the clinical effect.Results:The total effective rate was 93.8% (15/16) in the treatment group and 75.0% (12/16) in the control group. There was significant difference between the two groups ( χ2=8.19, P=0.042). After treatment, the level of AMS, WBC, CRP, PCT, AST, ALT and IL-6 in the treatment group were lower than those in the control group ( t values were 14.3, 7.24, 9.63, 5.48, 7.05, 7.33, 28.34, respectively, all Ps<0.05); After treatment, the time for body temperature to return to normal [(2.91±0.12)d vs. (3.78±0.38)d, t=8.76], the time for relief of abdominal distension pain [(4.77±0.68)d vs. (7.13±1.55)d, t=9.52], the time for recovery of bowel sounds [(3.90±1.80)d vs. (4.89±1.38)d, t=2.98] and the total hospital stay [(22.60±2.80)d vs. (30.37±3.89)d, t=7.88] in the treatment group were all significantly shorter than those in the control group ( P<0.01); APACHE Ⅱ, CTSI and the Modified Marshall Score in the treatment group were lower than those in the control group ( t values were 11.82, 12.72, 7.71, respectively, all Ps<0.01). Conclusion:Qingjie Huagong Decoction combined with ERCP and conventional western medicine therapy can reduce the level of inflammation in patients with cholelithiasis in the early stage of SAP, relieve clinical symptoms and improve clinical efficacy.