ObjectiveTo investigate the etiology and clinical features of intrahepatic cholestasis and the diagnostic value of whole exome sequencing （WES） through a retrospective analysis of the medical history， pathological results， and gene sequencing data of 62 patients with unexplained intrahepatic cholestasis. MethodsA retrospective analysis was performed for the clinical data of 480 patients who underwent WES due to unexplained liver function abnormalities in Nanjing Second Hospital from January 2017 to December 2023， among whom 62 patients with unexplained intrahepatic cholestasis were selected based on laboratory data， and a confirmed diagnosis was made based on imaging data， pathological findings， and gene sequencing data. The patients with unexplained intrahepatic cholestasis were analyzed in terms of demographic features， clinical manifestation， etiology spectrum， and genetic profile. ResultsA total of 62 patients with unexplained intrahepatic cholestasis were included， among whom there were 35 male patients and 27 female patients， with a median age of 42 （7 — ‍77） years. WES was used to make a definite diagnosis in 21 patients （33.87%）， among whom the patients with familial intrahepatic cholestasis accounted for the highest proportion of 52.38% （11/21）； genetic metabolic disorders were excluded by WES in 34 patients， with drug-induced liver injury and sepsis-associated liver injury accounting for the highest proportion of 55.88% （19/34）， followed by primary biliary cholangitis and primary sclerosing cholangitis accounting for 20.59% （7/34） and intrahepatic bile duct stones accounting for 17.65% （6/34）， while the patients with a lack of confirmed diagnosis accounted for 11.29% （7/62）. A total of 21 novel mutation sites which were not reported in previous articles were identified in this study. ConclusionGenetic metabolic disorders constitute a significant proportion of unexplained intrahepatic cholestasis， and WES plays a crucial role in the diagnosis of unexplained intrahepatic cholestasis.

ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. MethodsFrom July 19 to December 31， 2024， a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide， including their awareness and practice based on 18 questions regarding testing and referral， diagnosis and treatment， and follow-up. ResultsAmong all respondents， only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B， with an overall awareness rate of 22.0%. Only 20% ‍—‍ ‍40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy， while 80% ‍—‍ ‍100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year， 3 years， and 5 years were 67.5% 57.5% and 47.5%，respectively， showing a trend of gradual reduction， which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians， insufficient awareness of the disease among patients， and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection， diagnosis， treatment， and management” for patients with chronic hepatitis B in healthcare institutions， in order to promote the implementation of the guidelines.

Biochemical liver function tests are important methods to determine liver function in clinical practice， but abnormal liver biochemical parameters are not completely equivalent to liver damage. Some genetic and immune factors can also cause abnormal liver biochemical parameters， but with good prognosis in most cases. This article summarizes the causes of some benign abnormal liver biochemical parameters， so as to help clinicians to broaden their thinking of diagnosis and treatment， take into account genetic and immune factors， and avoid misdiagnosis and mistreatment.

Objective To investigate the expression of histone deacetylase(HDAC)isoforms in the frontal lobe,hippo-campus and liver of offspring rats delivered by rats with maternal immune activation and their correlation with the efficiency of prepulse inhibition(PPI％).Methods Ten pregnant Sprague-Dawley rats were randomly divided into the model group(n=5)and control group(n=5).The rats in the model group were injected with 10 mg·kg-1 polyinosinic-polycytidylic acid(Poly I:C)via the caudal vein on the 9th day of pregnancy,while rats in the control group were given the same volume of sterile physiological saline.After 3 h,blood was collected from the caudal vein,and the levels of interleukin(IL)-1 β,IL-6 and tumor necrosis factor-α(TNF-α)in the plasma of pregnant rats were detected by enzyme-linked immunosorbent assay to evaluate the immune activation status.The pregnant rats in the two groups were fed until natural delivery,the offspring rats were weaned on the 21st day after birth,and the male offspring rats were fed continuously.A prepulse inhibition test was performed at puberty(the 40th day after birth)to evaluate the spatial recognition memory and sensory gating function of the offspring rats.The expression levels of the HDAC gene family in the hippocampus,frontal lobe and liver of offspring rats were detected by real-time fluorescence quantitative polymerase chain reaction.Results The plasma IL-6,IL-1 β and TNF-α levels in the model group were significantly higher than those in the control group(P＜0.05).When the prepulse stimulation was 75 dB,the PPI％of the offspring rats at puberty in the model group was significantly lower than that in the control group(P＜0.05).When the prepulse stimulation was 80 and 85 dB,there was no significant difference in PPI％between the model group and the control group(P＞0.05).In the frontal lobe,the expression levels of HDAC3,HDAC4,HDAC8,HDAC9,HDAC10 and Sirt mRNA in the offspring rats in the model group were significantly lower than those in the control group(P＜0.05),while the expression level of HDAC5 mRNA was significantly higher than that in the control group(P＜0.05);there were no significant differences in the expression levels of HDAC1,HDAC2,HDAC6,HDAC7 and HDAC11 mRNA between the model group and the control group(P＞0.05).In the hippocampus,the offspring rats in the model group had significantly lower expression levels of HDAC1,HDAC8 and HDAC10 mRNA and significantly higher expression levels of HDAC2 and HDAC5 mRNA than those in the control group(P＜0.05);there were no significant differences in the expression levels of HDAC3,HDAC4,HDAC6,HDAC7,HDAC9,HDAC11 and Sirt mRNA between the model group and control group(P＞0.05).In the liver tissue,the expression levels of HDAC6 and HDAC10 mRNA of the offspring rats in the model group were significantly lower than those in the control group(P＜0.05);there were no significant differences in the expression levels of HDAC1,HDAC2,HDAC3,HDAC4,HDAC5,HDAC7,HDAC8,HDAC9,HDAC11 and Sirt mRNA between the model group and the control group(P＞0.05).The expression level of HDAC2 mRNA in the hippocampus of offspring rats in the two groups was negatively correlated with PPI％at 75 dB(r=-0.965,P＜0.05),the expression levels of HDAC10 and Sirt mRNA in frontal lobe tissues were positively correlated with PPI％at 75dB(r=0.946,0.925;P＜0.05).Conclusion Pregnancy Poly I:C infection has significant effects on the expression of HDAC family proteins in offspring rats,and which is related to the impairment of early sensory gating,this may provide new ideas for the research in pathogenesis and drug treatment of schizophrenia.

Objective:To investigate the iodine nutrition level and thyroid function status of pregnant women in Hubei Province.Methods:According to the requirements of "the National Iodine Deficiency Disorders Monitoring Program (2016 Edition)", in 2020, using a cross-sectional survey method, two mountainous counties and two plain areas in Hubei Province were divided into five districts: east, west, south, north, and central. One township (street) was selected from each district, and 20 pregnant women were selected from each township (street) as survey subjects. Urine iodine content and thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb)] were tested. Abnormal thyroid function rate and antibody positive rate were analyzed, and correlation analysis of thyroid function indicators was conducted (Spearman method). Results:A total of 321 pregnant women were included, including 43, 114, and 164 in early, middle, and late pregnancy, respectively; The median urinary iodine was 164.80 μg/L. The median serum FT 3, FT 4, TSH, TPOAb, TgAb levels were 4.10, 12.83 pmol/L, 1.85 mU/L, 15.84 and 13.35 U/ml, respectively. There were statistically significant differences in FT 3, FT 4, and TSH levels among different trimesters ( P < 0.05). According to Spearman's correlation analysis, FT 3 in early stage of pregnancy was negatively correlated with TSH and TPOAb levels ( r = - 0.46, - 0.33, P < 0.05), while TSH was positively correlated with TPOAb level ( r = 0.33, P = 0.032); there was a positive correlation between FT 4 and TgAb levels in middle stage of pregnancy ( r = 0.21, P = 0.032); there was a negative correlation between FT 3 and TPOAb levels in late stage of pregnancy ( r = - 0.19, P = 0.017); FT 3 and FT 4, TPOAb and TgAb levels were positively correlated throughout pregnancy ( P < 0.05). There was no correlation between urinary iodine content and thyroid function indicators ( P > 0.05). The total abnormal rate of thyroid function was 7.79% (25/321), with 16.28% (7/43), 5.26% (6/114), and 7.32% (12/164) in early, middle, and late pregnancy, respectively. There was no statistically significant difference in the abnormal rate of thyroid function among different pregnancy periods (χ 2 = 4.83, P = 0.097). The detection rates of hypothyroxinemia, hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism were 4.36% (14/321), 0.31% (1/321), 2.49% (8/321), 0.31% (1/321), and 0.31% (1/321), respectively. The positive detection rate of autospecific antibodies was 10.28% (33/321), with a TPOAb positive detection rate of 9.97% (32/321) and a TgAb positive detection rate of 5.30% (17/321). Conclusions:The iodine nutrition level of pregnant women in Hubei Province is at a suitable level, and the rates of abnormal thyroid function and thyroid autospecific antibody positive are relatively low. It is necessary to continuously monitor the iodine nutrition and thyroid function indexes of pregnant women, strengthen health education on the hazards of iodine deficiency during pregnancy, and minimize the harm to maternal and infant health caused by iodine deficiency.

Objective:To investigate the precipitating and aggravating factors in patients with fibromyalgia (FMS) compared to patients with rheumatoid arthritis (RA).Methods:This study was conducted from January 2015 to November 2021, using a cross-sectional survey research method, based on references to develop a patient-reported "onset and exacerbation triggers questionnaire", and surveyed patients with FMS and RA at the same time, and counted the types and proportions of onset and exacerbation triggers in the two groups of patients and used the chi-square test to make comparisons between the groups.Results:A total of 415 patients with FMS and 200 patients with RA participated the survey. 146 patients with FMS (35.2%) and 38 patients with RA (19.0%) reported morbidity triggers. Experiencing physical injury (71, 17.1%), wind-cold/cold-dampness (30 patients, 7.2%), mental stress (26, 6.2%), and exercise fatigue (10 patients, 2.4%) were the common morbidity triggers for FMS. More FMS patients reported to have experienced physical injuries and mental stress before the onset of the disease compared to RA patients [8.2%(17/200), χ2=5.41, P=0.020; 1.5%(3/200), χ2=6.82, P=0.009]. Exacerbation triggers were reported by 319 patients with FMS (76.9%) and 137 patients with RA (68.5%), in the order of weather changes (219 patients, 52.7%), physical labor (192 patients, 46.2%), mood swings (147 patients, 35.4%), sleep deprivation (145 patients, 34.9%), and mental stress (130 patients, 31.3%). The proportion of FMS patients with symptom exacerbation due to physical labor [46.2%(192/415)], mood swings[35.4%(147/415)], sleep deprivation[34.9%(145/415)], mental stress[31.3%(130/415)], and infection [9.3%(39/415)] was significantly higher than that of RA patients [35.0%(70/200), χ2=7.00, P=0.008; 19.5%(39/200), χ2=16.22, P<0.001; 13.5%(27/200), χ2=30.79, P<0.001; 17.5%(35/200), χ2=13.14, P<0.001; 3.0%(6/200), χ2=8.15, P=0.004). Conclusion:More than a third of FMS patients reported precipitating factors, and nearly four fifths FMS patients reported at least one aggravating trigger. FMS patients are likely to be more sensitive to environmental changes and perceived stress than RA patients.

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.

ObjectiveThis study aims to examine the effect of Rhei Radix et Rhizoma-Coptidis Rhizoma on reducing insulin resistance in db/db mice by regulating the adenylate activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1）/key molecule of autophagy， benzyl chloride 1 （Beclin1） pathway and elucidate the underlying mechanism. MethodSixty 6-week-old male db/db mice were studied. They were randomly divided into the model group， metformin group （0.26 g·kg^-1）， and low-， middle-， and high-dose groups （2.25， 4.5， 9 g·kg^-1） of Rhei Radix et Rhizoma-Coptidis Rhizoma. A blank group of db/m mice of the same age was set， with 12 mice in each group. After eight weeks of continuous intragastric administration， the blank group and model group received distilled water intragastrically once a day. The survival status of the mice was observed， and fasting blood glucose （FBG） was measured using a Roche blood glucose device. Fasting serum insulin （FINS） was measured using an enzyme-linked immunosorbent assay， and the insulin resistance index （HOMA-IR） was calculated. Hematoxylin-eosin （HE） staining was performed to observe the pathological changes in the liver of the mice. The protein expression levels of AMPK， Beclin1， autophagy associated protein 5 （Atg5）， and p62 in liver tissue were determined by using Western blot. The protein expression levels of autophagy associated protein 1 light chain 3B （LC3B） and ULK1 in liver tissue were determined using immunofluorescence. Real-time fluorescence quantitative PCR （Real-time PCR） was used to measure mRNA expression levels of AMPK， Beclin1， Atg5， ULK1， and p62. ResultCompared with the blank group， the model group exhibited a significant increase in body mass （P<0.01）. Additionally， the levels of FBG， FINS， and HOMA-IR significantly changed （P<0.01）. The structure of liver cells was disordered. The protein expression levels of AMPK， Beclin1， and Atg5 in liver tissue were significantly decreased （P<0.01）， while the expression level of p62 protein was significantly increased （P<0.01）. The expression levels of mRNA and proteins were consistent. Compared with the model group， the body mass of the metformin group and high and medium-dose groups of Rhei Radix et Rhizoma-Coptidis Rhizoma was significantly decreased （P<0.05）. FBG， FINS， and HOMA-IR were significantly decreased （P<0.05，P<0.01）. After treatment， the liver structure damage in each group was alleviated to varying degrees. The protein expressions of AMPK， Beclin1， Atg5， LC3B， and ULK1 were increased （P<0.05，P<0.01）， while the protein expression of p62 was decreased （P<0.01）. The expression levels of mRNA and proteins were generally consistent. ConclusionThe combination of Rhei Radix et Rhizoma-Coptidis Rhizoma can effectively improve liver insulin resistance， regulate the AMPK autophagy signaling pathway， alleviate insulin resistance in db/db mice， and effectively prevent the occurrence and development of type 2 diabetes.

BACKGROUND:After the treatment of femoral shaft fracture with the intramedullary nail,the third fracture open reduction indications are controversial.Some scholars believe that limited open reduction can achieve anatomical reduction,conducive to fracture healing;but some scholars believe that no open reduction of the third fracture still has a high fracture healing rate. OBJECTIVE:To investigate the effect of the circumference and displacement of the third fragment on fracture healing after intramedullary nailing of femoral shaft fractures with the third fragment. METHODS:A retrospective cohort study was conducted to analyze the clinical data of 142 patients suffered a femoral shaft fracture with a third fragment admitted to the Affiliated Lianyungang Hospital of Xuzhou Medical University from February 2016 to December 2021.The fracture were classified into three types according to the circumference of the third fracture with reference to the diaphyseal circumference at the fracture site:type 1 in 71 cases,type 2 in 52 cases,and type 3 in 19 cases.Referring to the diaphyseal diameter,the fractures were classified into three degrees according to the degree of the third fragment displacement:degree I in 95 cases,degree II in 31 cases,and degree III in 16 cases.All patients were treated with femoral interlocking intramedullary nails,and no intervention was performed for the displaced third fragment during the operation.Postoperative follow-up was performed to compare the fracture healing rate,healing time,and the modified Radiographic Union Scale for Tibia at month 9 after surgery in each group.The effect of third fracture fragment circumference and degree of displacement on fracture healing was assessed. RESULTS AND CONCLUSION:(1)All 142 patients were followed up for at least 12 months,with a mean of(14.7±4.1)months,and the overall healing rate was 73.4%.(2)When the third fragment was displaced by degree I,the healing rate,healing time,and modified Radiographic Union Scale for Tibia score at month 9 were not statistically significant among the three sub-groups of circumference classification.(3)When the third fragments were displaced by degree II or III,the healing rate and healing time were not statistically significant among the three subgroups of circumference classification;the modified Radiographic Union Scale for Tibia score at month 9 in the type 1 group was higher than that in the type 2 and 3 groups(P = 0.017).(4)Logistic regression analysis showed that a greater third fragment displacement and circumference were associated with lower fracture healing rates(P<0.05).(5)These findings indicate that in the treatment of femoral shaft fractures with third fragment by intramedullary nails,when the fracture fragment is displaced to degree I,the circumference size has little effect on fracture healing,and no intervention is required during surgery.When the third fragment is displaced to degree II or III and the circumference of which is type 1,a higher modified Radiographic Union Scale for Tibia score can still be obtained with no intervention of the third fragment.However,when the circumference is of type 2 or type 3,it significantly affects the fracture healing.Consequently,intraoperative intervention to reduce the distance of displacement of the fragment is required to lower the incidence of nonunion.The displacement of the third fracture fragments has a greater impact on fracture healing than their circumference.

Objective:To investigate the relationship between the expressions of checkpoint with forkhead-associated and ring finger(CHFR)and metastasis-associated protein 1(MACC1)and the sensitivity of patients with rectal cancer for neoadjuvant concurrent chemoradiotherapy(nCRT).Methods:The medical documents of 166 patients with rectal cancer admitted to First Hospital of Qinhuangdao from March 2017 to February 2022 were collected.All patients only received nCRT before surgery,and the radiotherapy adopted three-dimensional conformal intensity modulated radiotherapy,and chemotherapy adopted Capeox scheme.All patients successfully completed total mesorectal excision after 4-6 weeks of nCRT treatment.Immunohistochemical SP staining method was used to detect the protein expressions of CHFR and MACC1 in rectal cancer and its adjacent tissues.According to the tumor regressive grading(TRG)standard of the Joint Committee on Cancer Staging in the United States,75 patients who were grade 0-2 as TRG after nCRT were included in the nCRT insensitive group,and 91 patients who were grade 3-4 as TRG were included in the nCRT sensitive group.The expression levels of CHFR and MACC1 proteins in cancer tissues before and after treatment between the two groups were compared.And then,the relationship between clinically pathological characteristics of patients and nCRT sensitivity was analyzed,and the influencing factors of nCRT sensitivity were analyzed.The receiver operating characteristic(ROC)curves of them were drawn,and area under curve(AUC)values were calculated,and the predictive values of CHFR and MACC1 for the sensitivity of patients with rectal cancer to nCRT were further analyzed.Results:The CHFR positive expression rate in rectal cancer tissue was significantly lower than that in adjacent tissues of rectal cancer,and the MACC1 positive expression rate in rectal cancer tissue was significantly higher than that in adjacent tissues of rectal cancer(x2=81.373,87.150,P＜0.05),respectively.After 166 patients completed the nCRT treatment,there were 6 cases of TRG grade 0,8 cases of TRG grade 1,61 cases of TRG grade 2,59 cases of TRG grade 3 and 32 cases of TRG grade 4.The sensitivity rate of nCRT was 54.82%(91/166).The CHFR positive expression rate in the nCRT sensitive group was significantly higher than that in the nCRT insensitive group,and the MACC1 positive expression rate in the nCRT sensitive group was significantly lower than that in the nCRT insensitive group(x2=4.613,37.509,P＜0.05).The proportions of T4 stage and N+stage in the nCRT sensitive group were higher than those in the nCRT insensitive group,and the differences were statistically significant(x2=54.432,28.912,P＜0.05),respectively.The expressions of CHFR and MACC1 were respectively independent risk factor affected the sensitivity of patients with rectal cancer to nCRT[OR=2.456(95% CI:1.294-4.563),OR=3.281(95% CI:1.472-6.479),P＜0.05].The sensitivity and specificity of the combined detection of CHFR and MACC1 were respectively 65.89% and 69.46% in predicting the nCRT sensitivity for rectal cancer.The predictive value of the combined detection was higher than that of single CHFR detection and single MACC1 detection(AUC values of them were respectively 0.713,0.564,0.589,P＜0.05),respectively.Conclusion:CHFR and MACC1 are related to the sensitivity of patients with rectal cancer to nCRT,which means patients with high expression of CHFR and low expression of MACC1 are more sensitive to nCRT.Therefore,both of them may be indicators that predict the sensitivity of patients with rectal cancer to nCRT.