Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)₇TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)₇TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)₇TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.
Humans ; Male ; Glucuronosyltransferase/genetics* ; Adult ; Crigler-Najjar Syndrome/complications* ; Cholecystitis/etiology* ; Homozygote ; Mutation ; Pedigree

Objective:To elucidate the quasispecies variation of 3′ half-length genome in HIV-1 CRF103_01B-infected patients in Beijing using single genome amplification (SGA).Methods:This study enrolled six CRF103_01B-infected patients who were diagnosed during a drug resistance monitoring for newly diagnosed cases or newly treated cases with antiviral therapy in Beijing from 2017 to 2020. RNA was extracted from their plasma samples, and 3′ end of cDNA was diluted by serial dilution method after reverse transcription. Nested PCR was used to amplify the 3′ half-length genome sequences of HIV-1 quasispecies. MEGA 11 was used to construct Neighbor-Joining (NJ) tree and calculate the intrahost genetic distance. Genetic variation in HIV-1 quasispecies was visualized by online Highlighter tool. BootScan analysis was performed using Simplot 3.5 software to analyze inter-quasispecies recombination. Virus tropism was predicted by online Geno2pheno tool.Results:Among the six CRF103_01B-infected patients, five were men who have sex with men. A total of 144 3′ half-length genome SGA sequences (19-36 sequences/case) were obtained. The NJ tree based on the 3′ half-length genome of HIV-1 quasispecies revealed different degrees of genetic diversity. The HIV-1 quasispecies in BL4748-00 case of acute infection has the least variation with the intrahost distance of 0.002±0.000, showing genetic homogeneity. The quasispecies sequences from BL4981-00, BL3150-00 and BL3558-00 cases formed at least three subclusters, respectively, with different evolutionary directions, and their intrahost distance ranked from 0.031±0.004 to 0.016±0.002 (BL3150-00>BL3558-00>BL4981-00). The quasispecies sequences from the couple BL3022-00 (female) and BL3023-00 clustered into a large monophyletic cluster (bootstrap value=100%), and the intrahost distance of the latter (0.025±0.003) was higher than that of the former (0.019±0.002). Inter-quasispecies recombination was observed in BL3558-00 case. The quasispecies from the six patients were CCR5-tropic viruses.Conclusions:The diversity of quasispecies variation in CRF103_01B-infected patients is related to disease progress. Genetic homogeneity is observed in acute HIV infection, while multiple evolutionary directions are detected in chronic infection. Co-infection or superinfection cases are not found, but there are recombination events among quasispecies in some cases.

Objective:To explore the value of jellyfish sign, an abnormal ultrasonographic sign, in predicting adverse perinatal outcomes of women with complete placenta previa combined with placenta accreta spectrum disorders (PAS).Methods:This retrospective study analyzed the ultrasound images of 72 singleton gravidas, diagnosed with complete placenta previa combined with PAS, who underwent cesarean section at the First Affiliated Hospital of Nanjing Medical University between January 2020 and February 2023. Based on the presence and absence of the jellyfish sign in ultrasound images, these gravidas were divided into the jellyfish-sign group (15 cases, 20.8%) and the non-jellyfish-sign group (57 cases, 79.2%). The clinical data and perinatal outcomes of the two groups were analyzed. The adverse perinatal outcomes encompassed conditions such as abdominal aorta balloon block, uterine artery embolism, hysterectomy, postpartum hemorrhage, and neonatal intensive care unit (NICU) admission of their neonates. Statistical analysis was performed using two independent samples t-test, the Mann-Whitney U test and the Chi-square (or Fisher's exact) test. Results:(1) The jellyfish-sign group exhibited a higher parity [(1.6±0.7) times vs (1.2±0.6) times, t=2.01] and higher prenatal scores of placenta accreta [(12.3±1.5) scores vs (8.6±2.9) scores, t=6.59] than those in the non-jellyfish-sign group (both P<0.05). Among the 57 cases in the non-jellyfish-sign group, there were 14 cases of placenta creta (24.6%), 40 cases of placenta increta (70.2%), and three cases of placenta percreta (5.3%). Among the 15 cases in the jellyfish-sign group, nine cases were diagnosed with placenta increta, six with placenta percreta, and none with placenta creta. The difference in distribution between the two groups was statistically significant (Fisher's exact test, P<0.001). (2) Intraoperative blood loss [(for those who accepted abdominal aorta balloon block, 1 973±1 057) ml vs (1 211±576) ml, t=2.55], red blood cells transfused [4.0 U (2.0-23.0 U) vs 2.5 U (0.0-11.0 U), Z=－2.53], postoperative hospitalization time [(9.7±2.4) vs (7.5±2.2) d, t=3.36], the incidence of abdominal aorta balloon block [15/15 vs 38.6% (22/57), χ2=17.92], uterine artery embolism [for those who accepted abdominal aorta balloon block, 3/15 vs 1.8% (1/57), Fisher's exact test], and requiring blood transfusion [15/15 vs 63.2% (36/57), Fisher's exact test] were higher in the jellyfish-sign group than those in the non-jellyfish-sign group. However, the non-jellyfish-sign group had lower gestational age at delivery [(33.6±1.5) weeks vs (35.2±1.8) weeks, t=－3.24], and lower neonatal Apgar score at 1 min and 5 min [1 min: 8 scores (3-10 scores) vs 9 scores (4-10 scores), Z=－2.46; 5 min: 9 scores (7-10 scores) vs 10 scores (6-10 scores), Z=－2.02] (all P<0.05). There were no significant differences in emergency surgery rate, 24 h postoperative blood loss, neonatal birth weight, and proportion of NICU admission between the two groups. Additionally, no cases of hysterectomy or death were observed in the two groups. Conclusions:Ultrasound examination revealing jellyfish signs in patients with complete placenta previa and PAS is associated with an increased likelihood of adverse perinatal outcomes. Consequently, the management of these patients should be given greater attention.

Objective To investigate the effects of different ratios of ω-3 polyunsaturated fatty acids(ω-3 PUFA)on depression and cognitive impairment in patients with major depression.Methods A randomized,double-blinded controlled trial was used to randomly assign patients with depression to a cognitive improvement group,a depression improvement group,and a placebo group.The cognitive improvement group took 1388 mg of docosahexaenoic acid(DHA)and 692 mg of eicosapentaenoic acid(EPA)every day and the depression improvement group took 1248 mg of EPA and 832 mg of DHA every day.The placebo group took the same dose of soybean oil for 12 weeks,during which psychiatric medication was maintained.The 24-item Hamilton depression scale(HAMD-24)was used to evaluate depressive symptoms,and the standardized MATRICS consensus cognitive battery(MCCB)was used to evaluate cognitive function after 6 weeks and 12 weeks,respectively.Results The study recruited a total of 46 patients with depression including 22 in the cognitive improvement group,12 in the depression improvement group,and 12 in the placebo group.After 6 weeks of treatment,the HAMD-24 scores were significantly lower in the depression improvement group(19.00±10.70)and cognitive improvement group(16.58±9.39)than in the placebo group(31.10±10.03)(P<0.01).After 12 weeks of treatment,HAMD-24 scores were significantly lower in the depression improvement group(13.58±8.43)than in the placebo group(28.10±15.04)(P=0.02).No significant interaction effect was found on the cognitive assessment scores in any dimension after 6 weeks and 12 weeks of treatment(P>0.05).The incidence rate of adverse events in the depression improvement group was 16.7%(2/12),and no adverse events were reported in the other two groups.There was no significant difference in the incidence of adverse events among the three groups(P=0.13).Conclusion Treatment with ω-3PUFA for 6 weeks can improve the depressive symptoms of patients with depression.The formula with a higher ratio of EPA exhibits higher effectiveness while the two groups of ω-3PUFA formulas with different ratios do not improve cognitive function.

Objective To explore the clinical efficacy and safety of modified PPH combined with partial internal anal sphincterotomy in the treatment of circular mixed hemorrhoids.Methods Patients with annular mixed hemorrhoids were divided into two groups by a completely randomized controlled method.54 patients in the experimental group were treated with modified PPH combined with partial internal anal sphincterotomy,while 51 patients in the control group were treated with conventional PPH.The postoperative indicators,perioperative and long-term complication rates of the two groups were compared,and the clinical efficacy and safety were observed.Results The operation time in the experimental group was(48.35±4.37)minutes,which was higher than that in the control group(36.42 ±6.21)minutes(P＜0.05).The incidence of postoperative anastomotic stenosis in the experimental group was 1.9％,lower than 15.6％ in the control group(P＜0.05).Anal pain,urinary retention,first defecation time,long-term anal distention,the experimental group was significantly better than the control group,the difference was statistically significant(P＜0.05);The hospitalization time in the experimental group(4.8±0.62)days was not significantly different from that in the control group(5.1±0.54)days(P＞0.05).The amount of intraoperative bleeding and anastomotic bleeding in the experimental group[(17.28±2.22)ml,3.7％]were not significantly different from those in the control group[(16.75± 2.13)ml,3.9％](P＞0.05).Conclusion Compared with conventional PPH,the modified PPH combined with partial internal anal sphincterotomy slightly increases the operation time,but does not increase the risk of anastomotic bleeding,the incidence of rectal fistula,the amount of surgical bleeding,and the length of hospital stay.It can significantly improve postoperative anal pain,urinary retention,long-term distention symptoms,shorten the time of first defecation,ease the difficulty of defecation,and significantly reduce postoperative anastomotic stenosis,The long-term efficacy and safety are good.

Objective To observe the effect of prevention and treatment of gastrointestinal failure and coagu-lation function in severe acute pancreatitis(SAP)with single Rhubarb.Methods 68 caese with SAP were randomly divided into control group(n =34)and treatment group(n =34)by random number table.Both two groups were given routine western medicine,but in the treatment group the patients were additionally administered with single Rhubarb orally or nasal feeding.The time of first defecation,abdominal pain disappeared,bloating disappeared,upper abdomi-nal tenderness disappeared,serum amylase recovery,correction degree of coagulation function and average hospitaliza-tion days of the two groups were compared.Results The time of first defecation in the treatment group was (46.0 ± 18.0)h,which was (73.0 ±23.0)h in the control group,there was significant difference between the two groups(t =2.43,P <0.05).The time of abdominal pain disappeared[(4.3 ±1.2)d],bloating disappeared[(5.2 ±1.6)d], upper abdominal tenderness disappeared[(5.0 ±1.7)d],serum amylase recovery[(6.2 ±1.3)d]of the treatment group were significantly shorter than those of the control group[(5.6 ±1.7)d,(6.7 ±2.3)d,(6.4 ±2.1)d,(8.9 ± 1.6)d](t =2.36,2.17,2.60,2.48,all P <0.05).The average hospitalization days of the treatment group[(24.5 ± 12.3)d]was significantly shorter than the control group[(30.6 ±12.9)d](t =2.65,P <0.05).5 days after treat-ment,in the treatment group,the partially activated thromboplastin time(APTT)[(30.39 ±4.98)s]and prothrombin time(PT)[(12.65 ±1.32)s]were significantly shorter than the control group[(37.25 ±6.27)s,(14.87 ±1.68)s] (t =2.54,2.43,all P <0.05).The platelet count(PLT)and the fibrinogen(FIB)in treatment group were (186.30 ± 59.82)×109 /L and (3.89 ±1.17)g/L repectively,those in control group were (131.80 ±48.57)×109 /L and (5.29 ±1.33)g/L repectively,the differences were statistically significant between the two groups(t =2.16,2.83,all P <0.05).Conclusion The routine western medicine and additionally administered with single Rhubarb can effec-tively prevent and treat gastrointestinal failure,significantly improve coagulation function in SAP.

Aim To study the influence of Sodium fer-ulate ( SF) on bone metabolism in glucocorticoid–in-duced osteoporosis rats. Methods Thirty cases of fe-male Wistar Rats(3-month-old) were divided into con-trol group, model group and SF group ( low-dose group, middle-dose group, high-dose group ) by ran-domized block design. Double fluorochrome labeling with calcein was performed before necropsy. The left tibia was taken for bone histomorphometry. Results In static parameters, the proximal tibia cancellous bone trabecular thickness, trabecular quantity and area ratio were significantly reduced in model group compared with control group;while compared with model group, those were increased in middle and high-dose SF group. Trabecular separation degree was increased in model group compared with control group, while it was decreased in middle and high-dose SF group compared with model group. In dynamic parameters, the calcula-tion parameters of cancellous bone mark perimeter rate and the bone formation rate were increased in model group compared with control group, in middle and high-dose SF group the bone formation rate was in-creased compared with model group. In bone cells, os-teoclast number per mm, osteoblast number per mm, percent osteoblast surface perimeter and percent osteo-clast surface perimeter were increased in model group compared with control group. In growth-plate, the thickness of growth-plate was increased in model group compared with control group. In bone cells and growth-plate there was no statistical significance between treat-ment group and model group. Conclusion This study demonstrates that SF can increase bone mass and im-prove bone structure,which may be related to the im-provement of bone formation. SF is effective for GIOP in rats.

Objective To investigate the clinicopathologic features of intractable epilepsy related encephalitis.Methods The clinical and pathologic findings of 15 cases of intractable epilepsy after functional neurosurgical treatment were reviewed and analyzed retrospectively.Results All patients,including four male and 11 female,had medically intractable epilepsy.The mean age of onset for seizure was 5.3 years (1-15 years) and the disease duration was 4.7 years (0.5-15 years).A definite past history was identified in 11 patients,including viral encephalitis in nine patients,anoxia in utero and head trauma in one patient respectively.The extent and sites of involvement were different,including single cerebral hemisphere diffusely in five cases,multiple lobes in seven cases,and single lobe in three cases.Temporal lobe was involved in 13 cases,frontal lobe in eight,parietal lobe in eight,occipital lobe in seven,and insular lobe in four.Microscopically,all cases were characterized by perivascular inflammatory cells infiltration in the subarachnoid space.The focal cerebral cortex showed obvious atrophy with various degrees of the neuronal loss and glial proliferation,eventually leading to glial scar formation.In addition,microglia nodules,lymphatic cuff and neuronophagia were also observed.Seven cases of focal cortical dysplasia were identified among the 11 cases with adequate perilesional cerebral cortex.Hippocampus sclerosis was found in two cases.Intranuclear inclusions were seen in six cases,and these were immunopositive of cytomegaloviruslate antigen,and three cases also showed muhinucleated giant cells and calcifications.Conclusion Encephalitis is one of the common causes of refractory epilepsy,and may result in refractory epilepsy as a sequel.

Objective To analyze the clinical observation and incidences of complications of therapeutic post-endoscopic retrograde cholangiopancreatography (ERCP).Methods The clinical information of 1 482 cases of therapeutic ERCP was analyzed retrospectively.Results Among them,468 cases had nasal biliary drainage,532 cases had pancreatic or bile duct stent after endoscopic procedure and the other 482 case hadn't.For the drainage group, there were 396 cases of biliary stone,36 cases of simple dilatation of common bile duct,8 cases of biliary cyst,6 cases of strictured papilla,18 cases of inflammatory stricture of common bile duct,2 cases of sclerosing cholangitis and 2 cases of autoimmune pancreatitis.For the pancreatic or bile duct stent group,there were 483 cases of malignant bili-ary obstruction,13 cases of biliary stone,28 cases of pancreatic duct stone,3 cases of sclerosing cholangitis and 5 cases of inflammatory stricture of common bile duct.And there were 385 cases of biliary stone,36 cases of simple dilatation of common bile duct,38 cases of inflammatory stricture of common bile duct,11 cases of strictured papilla, 9 cases of pancreatic duct stone and 3 cases of biliary cyst for un -drainage group.The incidences of acute pancreati-tis and acute cholangitis (4.4%,2.6%)were higher in un -drainage group than the nasal biliary drainage group (1.5%,0.6%,P <0.05)or the stent group(1.7%,0.8%,P <0.05).The incidences of duodenum or biliary tract perforation and upper gastrointestinal hemorrhage(0.2%,1.2%)were not significantly different compared with the nasal biliary drainage group(0.2%,0.6%,P >0.05)and the stent group(0.4%,0.8%,P >0.05).The incidences of 4 kinds of complications were not significantly different between the nasal biliary drainage group and the stent group.Conclusion Endoscopic nasal biliary drainage or stent can prevent and treat some of therapeutic ERCP com-plications effectively.