Objective:To explore and analyze the clinical features of patients with immunoglobulin (Ig)G4-related hepatobiliary-pancreatic disease and the independent factors affecting the prognosis of IgG4-related sclerosing cholangitis (IgG4-SC).Methods:The clinical data of 179 adult cases diagnosed with IgG4-related hepato-pancreato-biliary disease in the Division of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2011 to December 2022 were retrospectively analyzed. Patients were divided into three groups: isolated IgG4-SC, IgG4-SC/type 1 autoimmune pancreatitis(type 1 AIP), and isolated AIP according to the clinical manifestations. Demographic characteristics, baseline biochemical immunological indexes, and imaging manifestations were analyzed. The treatment response rate and survival rate were compared. The COX proportional hazards model was used to analyze the independent factors related to prognosis.Results:The mean age of diagnosis of patients with IgG4-related hepatobiliary-pancreatic disease was 60.3±12.0 years. Males accounted for 74.9%, and the median follow-up time was 38 months. The 1-year clinical response rate of patients with isolated IgG4-SC was lower than that of IgG4-SC/AIP (67.9% vs. 91.7%, P=0.019), and the primary endpoint-free 5-year survival rate was significantly reduced (64.9% vs. 95.9%, P<0.001). COX regression analysis showed that having cirrhosis before treatment ( HR=6.708, P=0.004) and poor response after half a year of treatment ( HR=11.488, P=0.002) were independent risk factors associated with the occurrence of adverse events in hepatobiliary diseases among patients with IgG4-SC. Conclusions:The clinical response rate and survival rate of patients with isolated IgG4-SC are lower than those of patients with IgG4-SC/AIP. Patients with IgG4-SC who do not respond well at six months of treatment and who have progressed to cirrhosis before treatment are at significantly increased risk of adverse events.

In order to strengthen the supervision of the use of drugs in hospitals，the Sichuan Academy of Medical Sciences· Sichuan Provincial People’s Hospital took the lead in compiling the Principles for the Rational Use of National Key Monitoring Drugs （the Second Batch） with a number of experts from multiple medical units in accordance with the Second Batch of National Key Monitoring Rational Drug Use List （hereinafter referred to as “the List”） issued by the National Health Commission. According to the method of the WHO Guidelines Development Manual， the writing team used the Delphi method to unify expert opinions by reading and summarizing the domestic and foreign literature evidence of related drugs， and applied the evaluation， formulation and evaluation method of recommendation grading （GRADE） to evaluate the quality of evidence formed， focusing on more than 30 drugs in the List about the evaluation of off-label indications of drugs， key points of rational drug use and key points of pharmaceutical monitoring. It aims to promote the scientific standardization and effective management of clinical medication， further improve the quality of medical services， reduce the risk of adverse drug reactions and drug abuse， promote rational drug use， and improve public health.

Contrast-enhanced ultrasound (CEUS) is a new form of ultrasound (US) that can dynamically display microvessels in a highly sensitive manner. The purpose of this study was to investigate the efficacy of CEUS for characterizing testicular lesions in comparison with conventional US. Forty-seven patients with testicular lesions were enrolled. The histopathology results revealed that 31 cases were neoplastic (11 cases of seminomas, 8 nonseminomatous germ cell tumors, 8 lymphomas, 2 Leydig cell tumors, and 2 nonspecific tumors), and 16 cases were nonneoplastic (8 cases of infarctions, 3 epidermoid cysts, and 5 inflammation). The indicators of shallow lobulated morphology and cystic-solid echogenicity on conventional US were suggestive of germ cell tumors. More indicators on CEUS were found to be useful for characterizing testicular lesions. All the neoplastic lesions showed hyperenhancement on CEUS. Moreover, germ cell tumors presented with heterogeneous enhancement (73.7%, 14/19), a twisted blood vessel pattern, rapid wash-in and wash-out, and peripheral rim hyperenhancement signs. Lymphoma was characterized by nonbranching linear vessel patterns (87.5%, 7/8), rapid wash-in and slow wash-out. In nonneoplastic lesions, infarction and epidermoid cysts showed no enhancement, and abscesses were observed with marginal irregular enhancement. The sensitivity, specificity, and accuracy of CEUS for differentiating between neoplastic and nonneoplastic lesions were 100%, 93.8%, and 97.9%, respectively, and these values were higher than those for conventional US (90.3%, 62.5%, and 80.9%, respectively). CEUS can sensitively reflect the microvascular perfusion in testicular lesions and offers high accuracy for characterizing them.
Contrast Media ; Diagnosis, Differential ; Epidermal Cyst ; Humans ; Lymphoma ; Male ; Neoplasms, Germ Cell and Embryonal/diagnostic imaging* ; Sensitivity and Specificity ; Testicular Neoplasms/diagnostic imaging* ; Ultrasonography/methods*

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Birth Weight ; Body Height ; Fetal Growth Retardation ; Growth Disorders ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases

Adult ; Cesarean Section/statistics & numerical data* ; China/epidemiology* ; Female ; Humans ; Pregnancy ; Pregnancy Outcome/epidemiology* ; Risk Factors ; Trial of Labor ; Young Adult

Objective: To explore the clinical efficacy and safety of modified Huqianwan in treatment of rheumatoid arthritis (RA) liver-kidney Yin deficiency syndrome, and investigate its possible mechanism. Method: A total of 184 patients with RA liver-kidney Yin deficiency syndrome were randomly divided into Chinese medicine group (62 cases), western medicine group (57 cases) and integrated Chinese and western medicine group (65 cases) according to the digital table method. The patients in Chinese medicine group were treated with Huqianwan; the patients in western medicine group were treated with methotrexate tablets and leflunomide tablets; and the patients in integrated Chinese and western medicine group received Huqianwan+methotrexate tablets and leflunomide tablets,with a treatment course of 12 weeks in all groups. The pain visual analog scale (VAS), swelling and tenderness scores of 28 joints (DAS28), average hands grip strength, morning stiffness time and liver-kidney Yin deficiency syndrome differentiation of traditional Chinese medicine (TCM) syndrome score were compared between groups before and after treatment. The changes of erythrocyte sedimentation rate (ESR), C reactive protein (CRP), immunoglobulin (Ig) G, tumor necrosis factor-alpha (TNF-α) and rheumatoid factor (RF) were detected in all groups after treatment. Clinical efficacy, and incidence of adverse reactions such as gastrointestinal response, liver injury, leukopenia, serum glutamate oxaloacetic aminotransferase (GOT) and platelet (PLT) level changes were compared between the groups, so as to investigate the efficiency and safety of the different medicines. Result: After 12 weeks of treatment, the total clinical effective rate was 79.0%, 80.7%, and 92.3% respectively in Chinese medicine group, western medicine group, and integrated Chinese and western medicine group; the integrated Chinese and western medicine group was significantly better than the Chinese medicine group and western medicine group (P<0.01), but there was no difference between the Chinese medicine group and western medicine group. Every treatment group can effectively improve liver and kidney Yin deficiency syndrome in RA patients (P<0.05), and the effect in integrated Chinese and western medicine group was superior to that in Chinese medicine group (P<0.05); the effect in Chinese medicine group was superior to that in western medicine group (P<0.05). The incidence of adverse reactions was Chinese medicine group (1.61%, 1/62)Conclusion: The efficacy in treating RA liver and kidney Yin deficiency syndrome shows no significant difference between modified Huqianwan and methotrexate tablets+leflunomide tablets. In the treatment of RA liver and kidney Yin deficiency syndrome, Huqianwan has fewer adverse reactions. Huqianwan combined with methotrexate tablets+leflunomide tablets is superior to that in methotrexate tablets+leflunomide tablets in treatment of RA liver-kidney Yin deficiency syndrome.

OBJECTIVE: To research an appropriate estrogen therapy for in the pubertal development in Turner syndrome(TS)achievedbyestradiolvalerate.METHODS: In 57 TS girls of no spontaneous puberty or puberty arrest,we retrospectively studied pubertalstageanduterinedimensionduringtheestrogenreplacementtherapy.Datafrompatientrecordswascollected,described thepubertaldevelopingprocedure,and compared in groups which grouped by estrogen dosage to detect an appropriate dosage andthatcanleadabetterbreastanduterinedevelopment.RESULTS: The median age at start of puberty induction was 15.00 years,witharangeof11.5-21.0 years.(1)Breast development:Breast development to Tanner stage B2 was achieved in 0.29(0.25-0.33)years,stage B3 in 0.75(0.46,1.08)years,stage B4 in 2.20(0.92,3.08)years and B5 in 3.67(1.71,4.44)years.(2)Uterine development:The uterine volume and length in TS girls before treatment was 0.51(0.14,0.86)ml and 1.89(1.23,2.18)cm. We groupedthepatientsofTannerstageB2 ingroupsofestrogendosage≤0.5 mg/dand>0.5 mg/d and the uterine dimension and weightshowednodifference.Whenthepatientsweregroupedasgroupsofdosage<1.0 mg/d and group of dosage≥1.0 mg/d in stageB3,the uterine indexes in lower dosage group were less than group with larger dosage. When they were grouped as groups ofdosage<1.5 mg/d and ≥1.5 mg/d,the uterine volume 6.96(3.15-11.00)ml in lower dosage group was smaller than that in group withlargerdosage.CONCLUSION: During estrogen treatment in TS girls,normal breast development can be achieved. In a clinical setting,the uterine volume and length under pubertal induction developed properly with the breast stages progressing. when the breastdevelopedtostageB2,the uterine development was more dependable on estrogen. We recommend a low daily beginning estrogendosageuntilstageB2,which can be increased gradually after B2 to speed up the uterine development.

OBJECTIVE: To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy. METHODS: Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms. RESULTS: (1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment. (2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases; BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline. CONCLUSION Allogeneic NK cells have good safety and efficacy in the treatment of primary HCC. The anti-tumor effect of the allogeneic NK cells may play an important role in the activation of the patient's natural immune system and delay disease progression, suggesting that allogeneic NK cells combined with sorafenib may be a very effective treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.
Carcinoma, Hepatocellular ; Graft vs Host Disease ; Humans ; Killer Cells, Natural ; Leukocytes, Mononuclear ; Liver Neoplasms

Objective: To monitor the WT1 mRNA level and its dynamic changes in patients with myelodysplastic syndromes (MDS) after hypomethylating agents (HMA) , as well as to assess the significance of WT1 mRNA levels and its dynamic changes in evaluating the efficacy of HMA and distinguishing the disease status of heterogeneous patients with stable disease (SD) . Methods: Bone marrow or peripheral blood samples of 56 patients with MDS who underwent hypomethylating agents (≥4 cycles) from November 2009 to March 2018 were tested by real-time quantitative polymerase chain reaction (PCR) to detect the expression of WT1 mRNA, and to observe the correlation between the dynamic changes of WT1 mRNA expression and clinical efficacy and prognosis of patients. Results: WT1 mRNA expression levels of MDS patients decreased significantly after 3 cycles of hypomethylating agent treatment. Besides, the WT1 mRNA expression levels of patients increased significantly after diseases progression. According to the dynamic changes of WT1 mRNA expression levels during SD, 45 cases could be further divided into increased group and non-increased group. In those SD patients with increased WT1 mRNA expression level, the ratio of suffering disease progression or transformation to AML was 95.65% (22/23) , whereas the ratio turned to be 9.09% (2/22) for the non-increased group (χ(2)=33.852, P<0.001) . Compared with those SD patients reporting no increase in WT1 mRNA expression level, the overall survival[17 (95%CI 11-23) months vs not reached, P<0.001] and progression-free survival [13 (95%CI 8-18) months vs not reached, P<0.001] of those SD patients reporting increase in WT1 mRNA expression level were significantly shorter. Conclusion: WT1 mRNA expression level is a useful indicator to assess the efficacy of hypomethylating agents in MDS patients. Especially in patients with SD, detection of the changes in WT1 mRNA expression level is able to predict disease progression and help to make clinical decision.
Bone Marrow ; Humans ; Myelodysplastic Syndromes/genetics* ; Prognosis ; RNA, Messenger ; WT1 Proteins/genetics*