Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Off-label use means that the intended use of the drug is not included in the instructions approved by the National Medical Products Administration,including unapproved indication,dosage,the course of treatment,route of administration,or population.The formulation of Pharmaceutical Supply Services-Key Medications Management-Off-label Uses is based on relevant laws,regulations,normative documents,guidelines,literatures,and expert opinions,and follows the principles of scientificity,versatility,instructiveness,and operability.This standard regulates and standardizes the institutional and organizational construction,process management,and the whole process of quality management and evaluation improvement of off-label uses,which is the basis for medical institutions to carry out off-label uses management.This article introduced the formulation process of the off-label uses standard and analyzed the key contents of the standard,which would help medical institutions to better comply with and meet the requirements of this standard in the practice of off-label use management.

Drugs under special management include narcotic drugs,psychotropic drugs,toxic drugs for medical use,radiopharmaceuticals,and pharmaceutical precursor chemicals.Supervising and guiding the clinical use of drugs under special management is one of the important responsibilities of the Pharmaceutical Management and Drug Therapy Committee(Group)of medical institutions.The standard for drugs under special management is led by the Pharmaceutical Professional Committee of the China Hospital Association,which standardizes 16 key elements of organizational management,process management,and quality control management drugs under special management in medical institutions.It can guide the standardized implementation of Pharmaceuticals under special control work in various levels and types of medical institutions.This article elaborates on the methods and contents of formulating standards for Pharmaceuticals under special management,to provide reference and inspiration for medical institutions to carry out special drug drug management and daily related work.

The management of clinical application of antimicrobial drugs is an important part of the pharmaceutical management and pharmacy services in medical institutions.Based on national policies and regulations,this standard focuses on the whole life cycle of antimicrobial drugs in medical institutions.It is developed based on the principles of scientific validity,universality,guidance and operability,formed by sorting out problems,collecting opinions,expert argumentation and deliberation.It is the first group standard to standardize the clinical application management of antimicrobial drugs.This paper introduces and analyzes the team composition,problem sorting and compilation process,and various elements of the standard in the process of formulating the standard,and provide a reference for the majority of peers who use it.

Antineoplastic drugs refer to the drugs that act at the cellular and molecular levels to inhibit tumor growth or eliminate tumors through pathways such as cell killing,immune regulation,and endocrine regulation.Antineoplastic drugs generally including chemotherapeutic drugs,molecular targeted therapeutic drugs,immunotherapeutic drugs,and endocrine therapeutic drugs.The management and rational application of antineoplastic drugs in medical institutions are related to the safety of patient treatment.The standard for management of antineoplastic drugs use in clinical is compiled by the Pharmaceutical Affairs Committee of China Hospital Association,which specification requirements 18 key elements in the organizational management and system,medication management,drug monitoring and evaluation of antineoplastic drug management in healthcare institutions.This standard is applicable to all levels and types of healthcare institutions carrying out oncology diagnosis and treatment.This paper describes the methodology and basic content of the standard,hoping to providing a reference for medical institutions to carry out relevant work.

Objective To explore the therapeutic effect of plum blossom needle tapping combined with 3M physical therapy on temporomandibular joint disorders(TMD).Methods sixty TMD patients admitted to our hospital from January 2022 to December 2022 were selected and divided into an observation group and a control group,with 30 cases in each group.The control group received 3M physical therapy treatment,while the observation group received plum blossom needle tapping combined with 3M physical therapy treatment.Compared the changes in the Jaw functional limitation scale(JFLS),visual analogue scale(VAS),maximum active mouth opening(MMO),root mean square(RMS)surface electromyography(EMG)of the masseter muscle in mandibular position and under tight cotton swab testing between two groups of patients.Results After 4 weeks of treatment,the JFLS and VAS scores in the observation group were significantly reduced compared to those in the control group,while the MMO significantly exceeded that of the control group,indicating a statistically significant difference(P<0.05).After 4 weeks of treatment,the RMS value of the masseter muscle in the mandibular position decreased in the observation group,but increased in the tight bite cotton swab test.The muscle recruitment ability was significantly improved,and the degree of improvement was notably superior to that of the control group,with the difference being statistically significant(P<0.05).Conclusion The combination of plum blossom needle acupuncture and 3M physical therapy can notably alleviate pain,enhance maximum mouth opening,and improve mandibular function in TMD patients,accurate effect.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Objective:To evaluate the efficacy and safety of heating physiotherapy goggles in the treatment of meibomian gland dysfunction (MGD).Methods:A randomized controlled study was performed.Forty-four MGD patients were recruited in Wenzhou Medical University Eye Hospital from July 2021 to January 2022.Two patients were lost to follow-up.The patients were randomly divided into experimental group treated with heating physiotherapy goggles and control group treated with hot towels according to the random envelope method, with 21 patients (21 eyes) in each group.Throughout the study, the examiner was blinded.The data of the worse eye were analyzed.At baseline, 2 weeks and 4 weeks after treatment, the Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), fluorescein breakup time (FBUT), corneal fluorescein staining score (CFS), lid margin hyperemia score and meibomian gland function scores were measured to evaluate the efficacy; visual acuity, intraocular pressure and slit lamp microscopy were examined to assess the safety.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Wenzhou Medical University Eye Hospital (No.2021-177-K-153-01).Results:There were significant differences in OSDI scores between before and after treatment ( Ftime=16.528, P<0.001). No significant difference was found in OSDI scores between 30.46±17.31 at 2 weeks after treatment and 35.43±18.22 before treatment in control group ( P=0.405). The OSDI score at 2 weeks after treatment was 26.27±16.47, which was significantly lower than 39.24±17.96 before treatment in experimental group ( P=0.001). The eyelid margin hyperemia score was 0.0(1.0, 2.0) at 4 weeks after treatment in experimental group, which was significantly lower than 2.0(1.0, 3.0) in control group (Wald χ2=11.444, P=0.001). The morphologic scores of meibomian gland orifices at 2 and 4 weeks after treatment were both 1.0(0.0, 1.0) in experimental group, which were significantly lower than 2.0(1.0, 3.0) and 2.0(1.0, 2.5) in control group (Wald χ2=15.082, 23.172; both at P<0.001). The scores of meibum quality at 2 and 4 weeks after treatment were 1.0(0.5, 2.0) and 1.0(0.0, 1.5) in experimental group, which were significantly lower than 2.0(1.0, 2.0) and 2.0(1.0, 2.5) in control group (Wald χ2=4.638, 9.395; both at P<0.05). The scores of upper meibomian gland expressibility at 2 and 4 weeks after treatment were both 2.0(1.0, 2.0) in experimental group, which were significantly lower than 3.0(2.0, 3.0) and 2.0(2.0, 2.5) in control group (Wald χ2=6.489, 11.562; both at P<0.05). The score of lower meibomian gland expressibility at 4 weeks after treatment in experimental group was 1.0(0.5, 2.0), which was significantly lower than 2.0(2.0, 3.0) in control group (Wald χ2=24.085, P<0.001). The FBUT at 2 and 4 weeks after treatment were 3.00(1.75, 3.50) and 3.00(2.00, 4.00) seconds in experimental group, which were significantly longer than 1.00(0.75, 2.00) and 2.00(1.00, 3.00) seconds in control group (Wald χ2=8.576, 8.539; both at P<0.05). There were significant differences in TMH among different time points ( Ftime=8.874, P<0.001). In control group, the TMH at 4 weeks after treatment was (0.24±0.09) mm, which was significantly higher than (0.18±0.05) mm before treatment ( P<0.05). In experimental group, the TMH at 4 weeks after treatment was (0.23±0.09) mm, which was significantly higher than (0.17±0.05) mm before treatment ( P<0.05). Significant differences were found in CFS score among different time points (Wald χ2time=10.116, P=0.006). There was no statistically significant differences in CFS score between before and after treatment in control group (Wald χ2=1.781, P=0.410). In experimental group, the CFS scores at 2 and 4 weeks after treatment were 0.0(0.0, 1.5) and 0.0(0.0, 0.0), which were significantly decreased in comparison with 0.00(0.00, 4.00) before treatment (both at P<0.05). In experimental group, the visual acuity converted to the logarithm of the minimum angle of resolution at 2 and 4 weeks after treatment were 0.10(0.00, 0.22) and 0.10(0.00, 0.22), which was significantly better than 0.10(0.00, 0.40) before treatment (both at P<0.05). There was no significant change in intraocular pressure at different time points between the two groups ( Fgroup=0.432, P=0.515; Ftime=0.329, P=0.721). No serious adverse effects occurred in both groups during the follow-up period. Conclusions:Compared with hot towel therapy, the use of heating physiotherapy goggles can relieve ocular discomfort of MGD patients more rapidly and improve the function and status of the meibomian gland more significantly.Heating physiotherapy goggles can treat MGD safely and effectively.

Objective:To explore the effect and value of the active learning mode based on mind mapping in the teaching of medical service support for major disasters.Methods:A total of 90 undergraduate students of 2016 Clinical Medicine of Naval Medical University were randomly selected as research objects, and they were randomly divided into observation group and control group. The 45 students in the control group used the traditional teaching mode, and the 45 students in the observation group used the mind mapping-based active learning mode for major disaster rescue and medical survice. The teaching time of the two groups was 12 h. The theoretical examination of knowledge and practical skills of the two groups of students were compared after teaching, and the students' satisfaction with the application of mind mapping-based teaching model in the teaching of medical service support for major disaster rescue was investigated. EmpowerStats and R softwares were used for t test and Chi-square test. Results:There were 24 males and 21 females in the observation group, with an average age of (21.40±0.69) years old. There were 22 males and 23 females, with an average age of (21.71±0.55) years old. The theoretical performance of the observation group (91.38±4.37) was significantly higher than that of the control group (84.91±3.98) ( P<0.001), and the practical skill performance of the observation group (92.98±3.24) was significantly higher than that of the control group (87.38±3.80) ( P<0.001). At the same time, the students' satisfaction with teaching effect in the observation group was 82.2% (37/45), which was significantly higher than that in the control group (37.8%, 17/45). Conclusion:The active learning mode based on mind mapping focuses on cultivating students' independent learning, interactive exploration and clinical thinking ability, and has a broad application prospect in the teaching of medical service support for major disasters.