Volume 96  ·  Issue 48  ·  2016

With the aging of China's population, the number of osteoporosis patients is increasing, which is extremely harmful to the health of the elderly. Osteoporosis is a systemic and metabolic skeletal system disease characterized by low bone mass and destruction of bone microstructure, resulting in increased bone fragility, decreased bone strength and increased fracture risk. It can be divided into primary osteoporosis and secondary osteoporosis. Osteoporotic vertebral compression fracture (OVCF) usually refers to a disease in which the bone density and bone mass of the vertebral body of the spine decrease due to primary osteoporosis, and the bone strength decreases, resulting in compression fracture of the vertebral body with minor trauma or even without obvious trauma, mainly chest/low back pain, with or without lower limb neurological symptoms as clinical manifestations. OVCF causes fractured vertebral body height loss, resulting in kyphosis and intractable back pain. Kyphosis significantly decreases the pulmonary function of patients, leading to pneumonia and chronic obstructive pulmonary disease, gastrointestinal dysfunction, and seriously affecting the quality of life of patients. Due to pain, bed rest, and reduced activity, the patient's bone mass is further lost, and the continuous bone mass loss coupled with the forward movement of the body's center of gravity caused by kyphosis, the probability of re-fracture is also greatly increased^[1], thus falling into a vicious circle where many patients eventually die due to complications. The 4-year mortality rate of OVCF conservative treatment has been reported to be as high as 50%^[2,3]。 Therefore, the early intervention and standardized diagnosis and treatment of osteoporosis and OVCF have been paid more and more attention by the whole society.

Academician Fan Daiming discussed the theory of integrative medicine in his article: "Integrated medicine is to organically integrate the most advanced knowledge theory in various fields of medicine and the most effective practical experience in various clinical specialties, and modify and adjust it according to the reality of society, environment and psychology, so as to make it a new medical system that is more consistent and suitable for human health and disease treatment."^[1,2,3,4]。 The author believes that the "holistic discipline of cosmetic medicine in contemporary China", which has emerged since the middle and late 1980s, is a new medical discipline with holistic characteristics that a group of scholars in contemporary China consciously apply the holistic thinking method, follow the integration path, and through a series of theoretical studies, reintegrate the practical experience of related specialties in various fields of medicine, which is helpful to enhance the beauty of human life vitality^[5,6,7,8,9]。

To explore the diagnostic value of progesterone in 21-hydroxylase deficiency (21-OHD).

One hundred and ninety-three patients (female: 127, male: 66) with 21-OHD were recruited at Peking Union Medical College Hospital between January and December 2015. At the same time, 253 patients (female: 162, male: 91) with other disease were included as control, and their sex hormone and 17-OHP were measured simultaneously. The correlation between 17-alpha-hydroxyprogesterone (17-OHP) and progesterone was analyzed and the probability of progesterone as the diagnostic biomarker of 21-OHD was determined.

There was obvious positive correlation between progesterone and 17-OHP levels in subjects with different age and gender, and the correlation coefficient was from 0.775 to 0.878 (all P<0.001). Receiver operating characteristic curve (ROC) analysis showed that the area under curve was from 0.930 to 1.000 (allP<0.001) when using progesterone as the diagnostic biomarker.

Obvious positive correlation exists between progesterone and 17-OHP in patients with 21-OHD. The measurement of progesterone can be an assistant method for the diagnosis of 21-OHD.

To analyze the expression of soluble programmed death ligand 1 (sPD-L1) in the serum of patients with advanced epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma and to explore its clinical implications.

Seventy-two patients with EGFR mutated advanced lung adenocarcinoma (EGFR mutation group) were included from the Department of Respiratory Diseases in The Second Affiliated Hospital of Soochow University from May 2015 to July 2016. Thirty-one patients with advanced EGFR wild type (WT) lung adenocarcinoma [EGFR WT group, diagnosed via mini specimens from bronchoscopy or transthoracic needle aspiration biopsy (TNAB), matching in sex, age and tumor stage with EGFR mutation group] were also enrolled as controls. The sPD-L1 protein expression in serum was determined by enzyme-linked immunosorbent assay (ELISA) kit. According to the clinical response of two-month EGFR-tyrosine kinase inhibitor (TKI) treatment, all patients were divided into two groups: 36 cases in disease progression groups (PD group) and 36 cases in disease control group (DC group). The sPD-L1 level in peripheral blood between the two groups was analyzed. In EGFR mutation group, the relationship of serum sPD-L1 with TNM staging was analyzed. At the same time, the value of serum sPD-L1 and cancer embryo antigen (CEA) in clinical evaluation of advanced EGFR mutated lung adenocarcinoma was evaluated by analyzing the receiver operating characteristic (ROC) curve.

A lower level of sPD-L1 level in EGFR mutation group [0.75(0.15-2.78) μg/L] was found compared with the control group [1.56(0.85-3.29) μg/L] ( P<0.001). The expression of sPD-L1 in PD group was significantly higher than that in DC group [1.175(0.62-2.78) μg/L vs 0.625(0.15-2.27) μg/L,P<0.001]. High expression of sPD-L1 in the serum of patients with advanced EGFR mutated lung adenocarcinoma was closely correlated to lymph node metastasis and distant metastasis (χ²=10.985, 4.662; both P<0.05). The area under ROC curve of serum sPD-L1 and CEA was 0.893 (95%CI: 0.830-0.956) and 0.745(95%CI: 0.652-0.839) respectively. Youden index was the maximum when the cutoff value of sPD-L1 was set to 0.815 μg/L, and the sensitivity and specificity were 77.8% and 91.4%, respectively.

After EGFR-TKI treatment, the level of sPD-L1 in the serum of patients with advanced EGFR mutated lung adenocarcinoma is lower, which suggests that sPD-L1 expression may depend on the regulation of EGFR signaling pathway. The level of sPD-L1 can reflect the clinical response of EGFR mutated lung adenocarcinoma to EGFR-TKI.

To summarize the initial experiences of applying sacral neuromodulation (SNM) for refractory interstitial cystitis/pelvic pain syndrome (IC/PPS).

From January 2013 to August 2016, 26 patients with refractory IC/PPS (including 5 males and 21 females) treated with SNM were recruited in Beijing Chaoyang Hospital and Hebei Yanda Hospital in this retrospective study. The data before operation, after implantation of stage Ⅰ tined lead, and during short-term follow-up after implantation of stage Ⅱ implanted pulse generator (IPG) were compared in order to observe the improvement of relevant symptoms, and to summarize the effectiveness and safety of SNM for IC/PPS.

All the 26 patients received stage Ⅰ tined lead implantation under local anesthesia, of whom 7 patients finally had the tined lead removed under local anesthesia because of poor testing effects. And 19 patients chose embedding of IPG at the end of stageⅠ, with the conversion rate from stage Ⅰto stage Ⅱ being 73.1%. The mean follow-up time after stage Ⅱ was 12.1 months. The data at the end of follow-up compared with those before treatment were: voiding frequency in 24 hours 24.3±9.6 vs 13.5±5.7, nocturia 4.6±2.2 vs 2.7±1.5, average voiding amount (109.4 ±45.3)vs(172.6±61.6) ml, O′leary-sant scale score 26.0±3.1 vs 17.0±3.8, quality of life (QOL) score 5.7±0.4 vs 3.3±1.3, sex rating 5.4±1.4 vs 2.9±1.6, and Numeric Pain Intensity Scale 8.4±1.7 vs 3.9±1.2 (all P<0.05). During the follow-up period for the 19 patients, 11 showed symptoms relieve without recurrence, 5 patients had slightly symptoms recurrence and 3 patients had severe recurrence of pelvic pain and frequent urination. About 42.1%(8/19) patients received reprogramming, the average reprogramming rate being 1.73/person. And 84.2% (16/19) patients had symptoms improvement greater than 50% after stage Ⅱ IPG implantation.

SNM is an effective, safe and minimally invasive procedure for refractory IC/PPS. IC/PPS is a good indication for SNM with a high conversion rate from stage Ⅰ to stage Ⅱ. Patients should be followed up regularly after operation, and reprogramming should be arranged according to the degree of symptom improvement.

To analyze the clinical features and outcomes of congenital adrenal hyperplasia (CAH) with adenomatoid adrenal gland.

Nineteen patients clinically confirmed as CAH with adenomatoid adrenal gland, from 2008 to 2015 in Deparment of Endocrinology of Chinese PLA General Hospital, were retrospectively analyzed, and the outcomes of the treatment were followed up.

Seventy-six patients were clinically confirmed as CAH, from 2008 to 2015 in PLA hospital. Nineteen of them have accompanied with adenomatoid adrenal gland. Of the 19 confirmed cases, 7 were male, and 12 were female. The mean age was (33.3±14.8) years old. Nineteen confirmed cases were consisted of 10 cases of 21-hydroxylase deficiency (OHD), 6 cases of 17α-OHD, and 3 cases of 11β-OHD. Of the 19 cases, 5 cases presented with adrenal hyperplasia with left side adenomatoid solid lesion, 2 cases presented with adrenal hyperplasia with right side adenomatoid solid lesion, and 8 cases presented with double side adenomatoid solid lesion. The proportion of adrenal hyperplasia with unilateral cystic or calcified changes was 21.1%. Nine of the 19 patients underwent operation or fine needle biopsy. The pathology showed 7 adenomas (21-OHD/17α-OHD 5/2) and 2 myelolipomas (21-OHD/17α-OHD 1/1). Four patients were admitted into hospital because of the incidentaloma, while others because of the clinical symptoms. The average follow-up time was 31 months. CT images were rechecked among 7 patients. After the treatment, 1 patient′s tumor shrunk, 4 cases had no recurrence, 1 case′s tumor disappeared, and the other one case had no change. Symtoms of eleven followed-up patients relieved.

The image of adrenal of CAH with adenomatoid adrenal gland is various. It may occur in each type of CAH presented as unilateral or bilateral, adenoma or myelolipoma.

To study the safety and feasibility of using monopolar coagulation in sutureless laparoscopic partial nephrectomy (LPN).

From February 2015 to March 2016, sutureless LPN using monopolar coagulation was performed on 25 patients with renal tumors. Mean patient age was 50 years (range 31 to 68). Mean tumor size was 4.1 cm (range 1.2 to 10.1). Mean RENAL nephrometry score was 6.1 (range 4 to 12). The renal hilar vessels were clamped in 14 surgeries, whereas 11 surgeries were carried out without clamping. The tumors were resected by cold scissors and monopolar hook. The tumor beds were coagulated by monopolar hookrepeatedly in spray and fulgurate modes.N-butyl-2-cyanoarcrylat (NBCA) was used in 13 patients when bleeding was observed after coagulation.

Mean operative time was 129.6 mins (range 70 to 300). Mean warm ischemic timein clamped cases was 22.6 min (range 15 to 32). Mean estimated blood loss was 166 ml (range 10 to 800). Mean hospital stay was 16.2 days (range 7 to 36). Two patients received blood transfusions. One patient received open surgery and suturing repair after failure of selective arterial embolization for postoperative hemorrhage. Two patients had urine leakage without any intervention.

The technique using monopolar coagulation in sutureless LPN was safe and feasible. For exophytic and small tumors, the off-clamped technique could berecommended.

To investigate the effect and mechanism of intermedin (IMD)on the apoptosis of BMSCs induced by H₂O₂ and its mechanism.

BMSCs being cultured in vitro. After 30 min pretreatment with 10^-6mol/L IMD, cells were cultured in presence of 100 μmol/L H ₂O₂ for 2 hour, cell apoptosis was determined by flow cytometry; Apoptosis related protein expression was determined by Western blotting and immunofluorescence; Protein and phosphorylation of ERK1/2 was detected by Western blotting and observe the influence of IMD after pretreatment with inhibitor of ERK1/2.

IMD could increase phosphorylation of ERK1/2 pathway of BMSCs (P<0.01). Pretreatment of IMD could decrease BMSCs apoptosis induced by H₂O₂, and up regulation expression of Caspase-3 and Bax, down regulation expression of Bcl-2 (P<0.01), and the effect was abrogated by U0126.

IMD can activate ERK1/2 signaling pathway of BMSCs, and can regulate the expression of apoptosis related proteins. Furthermore, it can protect BMSCs from apoptosis induced by H₂O₂. Activation of ERK1/2 pathway was involved in the effect of IMD on apoptosis.

To investigate whether glabridin has a beneficial effect on lipopolysaccharide (LPS) induced acute respiratory distress syndrome (ARDS) in rats, and to explore the possible underlying mechanisms.

Thirty-two Wistar rats were randomly assigned into control group, model group (LPS group), glabridin group (GLA group), and ulinastatin group (UTI group), with 8 rats in each group. ARDS rat model was reproduced by intraperitoneal injection of LPS (10 mg/kg). The rats in the control group received an equal volume of normal saline at the same times. The rats in GLA group were gavaged by glabridin (30 mg/kg). The rats in UTI group were injected ulinastatin (20 000 U/kg). Animals were sacrificed 12 hours after LPS challenge. Plasma and lung tissue samples were collected. Histopathological evaluation, lung wet/dry (W/D)ratio, tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase(SOD)were analyzed. Immunohistochemical method was used to detect the protein expression of p38MAPK and ERK. Western blot method was used to detect the changes of p38 mitogen activated protein kinase (p-p38MAPK) and phosphorylated extracellular regulated protein kinases (pERK) protein expression in lung tissues.

In the control groups, lung tissue showed a normal structure and clear pulmonary alveoli under a light microscope. In the model group, ARDS characters such as extensive thickening of the alveolar wall, significant infiltration of inflammatory cells, demolished structure of pulmonary alveoli, and hemorrhage were found. In the GLA and UTI treatment group, these pathological changes in lung were markedly alleviated compare with LPS-induced ARDS group. Compared with control groups, lung W/D ratio, TNF-α and IL-18 in plasma, and lung MDA, NO levels in lung homogenates of the LPS group were increased significantly, while the lung SOD levels of the LPS group were decreased. Compared with the LPS group, lung W/D ratio, TNF-α and IL-18 in plasma , and lung MDA, NO levels in lung homogenates of the GLA group and UTI group were decreased significantly, while the lung SOD levels of the GLA and ulinastatin groups were increased [TNF-α(μg/L): 51.7±10.3 vs 105.7±30.5, IL-18(μg/L): 37.9±13.9 vs 49.2±14.5, MDA (nmol/mgprot): 2.87±0.62 vs 3.81±0.42, NO(μmol/L): 18.96±0.79 vs 28.58±2.51, SOD(U/mgprot): 115.5±15.2 vs 75.9±14.0, allP<0.05]. Immunohistochemistry showed that the positive expressions of p38MAPK and ERK in cytoplasm and nucleus of the glabridin and ulinastatin treatment group were significantly lower than those of the model group. Western blot showed that compared with the control group, the p-p38MAPK and pERK protein expression in LPS group were significantly increased. And the glabridin and ulinastatin inhibited the protein expressions compared with model group.

Traditional Chinese medicine glabridin significantly ameliorated the lung injury induced by LPS in rats via reducing inflammation which caused by the inhibition of p38MAPK and ERK signaling pathway and antioxidant effect.

To investigate the effect of different doses of recombinant parathyroid hormone (PTH) (1-34) on osteolysis in a murine calvarial model.

In total, 48 adult male C57BL/J6 mice were randomly divided into four groups: the sham group, the vehicle group, the low dose-, and high dose PTH group (n=12 each group). Mice in the PTH groups were treated with local injection of recombinant PTH at 30 or 60 μg·kg ^-1·d^-1, intermittent injection 3 times per week for two weeks. Mice in the sham and vehicle groups received local injection of saline daily. Two weeks after surgery, calvarial tissue and peripheral blood were harvested for further analysis. Osteolysis was assessed by micro-computed tomography. The mRNA and protein expression of osteoprotegerin (OPG) and receptor activator for nuclear factor-κB Ligand (RANKL) of calvarial tissue and peripheral blood were tested by real-time PCR and ELISA, respectively.

Compared with the vehicle group, PTH treatment significantly inhibited the severity of osteolysis and improved the bone volume. Real time-PCR and ELISA showed that PTH significantly increased the mRNA and protein expression of OPG and reduced the RANKL/OPG ratio.

These findings suggest that local application of PTH could effectively inhibit wear-particle-induced-osteolysis in a murine calvarial model.

To study the prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) and its relationship with traffic accidents in the professional drivers.

Questionnaires of OSAHS were sent to 950 professional drivers who had annual physical examination at the Central Hospital of Jiading District in Shanghai from October 2014 to September 2015. Those with moderate to severe snoring and/or Epworth Sleepiness Scale (ESS)≥9 performed the home sleep testing. All drivers were divided into OSAHS and non-OSAHS according to the survey and monitoring. The following parameters were compared such as driving ages, neck circumference, body mass index (BMI), average night sleep time, ESS, hypertension, diabetes, hypertrophy of tonsil and the incidence of traffic accidents. The risk factors of traffic accidents were analyzed by multivariate Logistic regression.

Totally 826 responses were eligible, including 578 (70.0%) with self-reported snoring. There was measurement failure involving 3 of 233 the home sleep testing due to sensor off, 823 subjects were included in the study. The prevalence of OSAHS was 13.5% (111/823). The mild, moderate and severe OSAHS were 47, 38 and 26 cases respectively. There were 712 drives without OSAHS. The neck circumference[(39.8±3.8) vs (39.0±3.0) cm]and BMI[(26.7±4.2) vs (24.4±3.8) kg/m²]were significantly higher in the drivers suffering from OSAHS (all P<0.05). The percentage of ESS≥ 9 (57.7% vs 12.6%), hypertension (27.9% vs 5.9%), diabetes (4.5% vs 1.1%), hypertrophy of tonsil (7.2% vs 2.3%) were higher in the drivers with OSAHS (allP<0.05). There were no significant difference in driving ages and average night sleep time between two groups (allP>0.05). The overall incidence of traffic accidents was 5.8% (48/823) in a year. The percentage was respectively 17.1% (19/111) in OSAHS and 4.1% (29/712) in non-OSAHS (P<0.001). Multiple logistic regression analysis showed that sleepiness (OR=30.578, 95%CI: 10.699-87.394; P<0.001), OSAHS (OR=14.062, 95%CI: 4.791-41.269; P<0.001) and vehicle years (OR=2.345, 95%CI: 1.183-4.646; P<0.05)were the risk factors, while the average night sleep time (OR=0.037, 95%CI: 0.014-0.098; P<0.001) was the protective factor.

Professional drivers have higher prevalence of OSAHS, which contributes to the increased risk of traffic accidents.

A 28-year-old female was admitted to Peking Union Medical College Hospital on June 30, 2016 due to recurrent head, face and limbs numbness and convulsions for 21 years. Twenty-one years ago, the patient began to have intermittent numbness on the top of the head without obvious trigger, which then involved the face, tongue, hands and lower limbs. Then, the face and hands twitched, manifesting as twitching of eyelids and mouth corners, and the hands appeared as "midwife-like hands", which lasted 5~6 minutes and could be relieved by itself. The shortest attack cycle was about 2 weeks, and the longest was unknown. Nine years ago, when the patient's symptoms recurred, he went to the local hospital to check the blood potassium of 2.6 mmol/L. The blood pressure was normal, and no abnormalities were found on head CT. The symptoms were relieved after oral and intravenous potassium supplementation, and no further diagnosis and treatment was made. After that, there was occasional numbness in the head, face and limbs, no further convulsions, and no regular electrolyte review. In August 2015, the patient's blood potassium was 2.5 mmol/L during the prenatal examination at about 8 weeks of pregnancy, and the blood magnesium decreased (the specifics are unknown). At that time, the patient had no discomfort and no intervention. At about 20 weeks of pregnancy, there was threatened premature delivery. The blood potassium was 1.9 mmol/L and the urine potassium was 76 mmol at 24 hours. At that time, there was numbness in the head, face and limbs, but there was no convulsion. After oral treatment with 6 tablets of magnesium potassium aspartate/d (each tablet contained 0.14 g of magnesium aspartate, equivalent to 11.8 mg of magnesium ions; 0.158 g of anhydrous magnesium potassium aspartate, equivalent to 36.2 mg of potassium ions) and 4.5 g/d of potassium chloride, the blood potassium could rise to 3.0~3.5 mmol/L. In the second and third trimester of pregnancy, fasting blood glucose was found to be 6~7 mmol/L (details unknown), and the highest blood pressure was 160/90 mmHg (1 mmHg =0.133 kPa). The diagnosis of "gestational diabetes and pregnancy-induced hypertension" was performed. Intrauterine induction of labor was performed due to fetal death at 35 weeks of pregnancy, and then there was no regular potassium supplementation treatment and regular follow-up. Weight loss of about 5 kg in the last 3 months. Past history: Polycystic ovary syndrome was diagnosed in an external hospital, the specificity is unknown. Blood glucose and blood pressure were normal before pregnancy and after delivery to hospital admission. Personal history is not special. Menarche 14 years old, menstrual days 7 days, menstrual cycle 1 to 6 months, last menstruation 15 June 2016, G₁P₀。 Family history: There is no family history of similar diseases and hereditary diseases.

A 14-year-old male was admitted to the hospital on February 2, 2016 due to "the discovery of a mass in the right calf for 8 months, facial nodules for 3 weeks and chest pain for 2 days". In June 2015, the patient discovered a dark red patch on the skin on the inner side of his right calf (Figure 1), about 1.0 cm in diameter, not higher than the skin surface, does not fade when pressed, and has no redness, swelling, heat, pain, ulceration or fluctuating feeling. The posterior plaque gradually increased and became nodular, higher than the skin surface, with dark red and uneven color, without redness, swelling, heat, pain and ulcer. On January 10, 2016, a blue-purple nodule on the left side of the upper lip appeared, 1 cm in diameter, higher than the skin surface, and did not fade when pressed. The posterior nodules gradually spread to the face and chest and back (Figure 2), 0.5-3.0 cm in diameter, with the same character as labial nodules. Forehead skin biopsy was taken from the dermatology department of our hospital. Pathology: mild hyperkeratosis of the epidermis, atrophy and thinning of the spinous layer, and no lymphocytes migrated into the epidermis. The lymphocytes around the dermal blood vessels and appendages were diffuse, flaky and massive infiltration; Immunohistochemistry: CD3 negative (–), CD4 positive (+), CD8 (–), CD20 (–), CD79a (–). On February 2, 2016, there was no obvious trigger for sudden severe pain in sternum and ribs, which was a sense of pressure, which could be aggravated when holding breath and deep breathing. There was no fever, cough, palpitations, chest tightness, sweating, abdominal pain, diarrhea, dizziness, headache, nausea, vomiting, and convulsions. Blood routine in our hospital outpatient and emergency department: white blood cells 30.71×10⁹/L, red blood cells 4.89×10¹²/L, hemoglobin 150 g/L, platelets 124×10⁹/L. Blood smear: 26% of blasts. Blood coagulation, liver and kidney function were normal. Thoracic, abdominal and pelvic enhanced CT: multiple enlarged lymph nodes in bilateral neck, axilla and right diaphragmatic angle area; Hepatosplenomegaly; Multiple enlarged lymph nodes in the mesenteric area, retroperitoneal, pelvic cavity and bilateral groin. Bone marrow puncture, bone marrow smear (Figure 3): Bone marrow hyperplasia is active, and the whole film is mainly prolymphocytes, accounting for 88.5%; The cells vary in size, mainly large; Peroxidase (POX) staining (–), glycogen staining positive rate: 27%, bead-like; Acute lymphoblastic leukemia type L2 (ALL-L2). The outpatient clinic is "ALL-L2" income in our hospital. Since the onset of the disease, the spirit, appetite and sleep are good, the second stool is as usual, and the weight has not changed significantly. Past history, personal history: Nothing special. Family history: The mother suffered from hepatic hemangioma, which has been operated on, and the father and first sister are in good health. Grandmother died of ovarian cancer.

The proband female, 29 years old, Dong nationality, came to the Department of Eugenics Genetics of Guizhou Maternal and Child Health Hospital in November 2015 because she was 16 weeks pregnant and had deafness in both families of her husband and wife. The complaint is that I have no symptoms of deafness and no other systemic diseases. His parents have no symptoms of deafness, and there are patients with deafness in his family. The onset age ranges from 1 to 40 years old. There is no diagnosis and treatment. The specific medication is unknown, and there are no other organ and system diseases. The husband of the proband, 35 years old, Han nationality, has gradually declined in hearing in the past three years, has no other organ system diseases, has no diagnosis and treatment, and his parents have no symptoms of deafness. There are deaf patients in his family, who develop the disease at the age of 1 to 20, has no diagnosis and treatment, and the medication is unknown. Our hospital conducted a genetic test of deafness on the couple, and found that both spouses were 1555A>G mutant in mitochondrial mtDNA 12S rRNA gene. Prenatal diagnosis was recommended, but the two refused to do it.

A 41-year-old male was admitted to the Department of Hematology, Kaifeng Central Hospital, Henan Province on January 6, 2014 due to "elevated white blood cells found in physical examination for 1 d". Physical examination after admission: body temperature 36.5℃, pulse 88 beats/min, breathing 22 beats/min, blood pressure 120/80 mmHg (1 mmHg =0.133 kPa), normal development, no facial edema, no pale palpebral conjunctiva, clear mind, general spirit, no yellowing stains and bleeding spots on the skin and mucous membranes of the whole body, no swelling of superficial lymph nodes, no cyanosis of the lips, no tenderness in the sternum, clear breathing sounds in both lungs, no dry and wet rales, heart rate 88 beats/min, harmonic heart rhythm, no palpation of the liver under the costs, mild swelling of the spleen, 2 cm below the left rib, soft texture, no tenderness, no percussion pain in the kidney area, and no edema in both lower limbs. Auxiliary examination: Blood routine on January 6, 2014 showed: white blood cells 45.12×10⁹/L, hemoglobin 122 g/L, platelets 534×10⁹/L, peripheral blood smear showed: progranulocytes 0.02, mesomyelocytes 0.05, metamyelocytes 0.04, neutral rod nuclear cells 0.16, neutral lobulated nuclear cells 0.43, lymphocytes 0.13, monocytes 0.01, eosinophils 0.06, basophils 0.10. Neutrophil alkalase integral staining: 1% positive, 1 point integral. Bone marrow image: The proliferation of nucleated cells in bone marrow was obviously active, with a granule-red ratio of 15.4:1, abnormal granulocyte proliferation accounting for 92.5%, and primitive granulocytes 1.5%. The proliferation of granulocytes in mesomyelocyte and below stages was the main one, among which the proportion of eosinophils and basophils increased significantly, accounting for 7.5% and 9.0%, respectively, and the morphology was roughly normal. Bone marrow biopsy (Wuhan Kangshengda Medical Laboratory): bone marrow tissue was submitted for examination, and the hematopoietic tissue volume was>80%, showing extremely active bone marrow hyperplasia; Granulocyte precursor cells are visible, with abnormal localization (abnormal localization of precursor cells); Erythroid hyperplasia is low, megakaryocytes 5~8/HPF, with a single round nucleus; Lymphocytes and plasma cells are visible; Eosinophils are scattered and easily visible; Focal hyperplasia of fibroblasts. Immunotyping: Gate analysis was set on the CD45/SSC dot plot. Abnormal cell populations could be seen in the original cell distribution area, accounting for about 6.7% of nuclear cells, expressing HLA-DR, CD13, CD33, CD38, CD117, some cells expressing CD34, and a few cells expressing CD7. Considering the possibility of chronic myeloid leukemia (CML). Karyotyping: 46 XY, t (9; 22) (q34; q11) [20]. Fusion gene (Wuhan Kangshengda Medical Laboratory) BCR-ABL210/ABL =0.86. Final diagnosis: CML chronic phase, low-risk group with Sokal score.

A 46-year-old female was admitted to the hospital mainly for episodic left limb lifting and weakness, with memory loss for 50 d. On January 28, 2016, the patient had episodic left limb lifting and weakness without obvious trigger. Each attack lasted for 2 to 3 s, and it could be relieved after the attack. Falls could occur during the attack while walking. Unconscious loss, no limb twitching, fecal incontinence, tongue bite; There is no obvious aura before the attack, and the attack occurs several times a day. The patient went to a local hospital, considered "epilepsy and encephalitis", and was treated with oxcarbazepine, oxiracetam and gangliosides. During hospitalization, the obvious cognitive decline was mainly manifested as near-memory loss and computing power. On February 29, 2016, the frequency of episodic symptoms in the left limb increased compared with before, reaching dozens of times a day, which affected sleep at night. On March 17, 2016, he went to the Department of Neurology, Xuanwu Hospital, Capital Medical University. Auxiliary examination: Hematological examination: There were no obvious abnormalities in blood, urine and stool routine, and the biochemical, coagulation and antinuclear antibody profiles were normal. Serum sodium 128 mmol/L, cerebrospinal fluid biochemistry normal, cerebrospinal fluid routine: white blood cell count 3×10⁶/L, blood and cerebrospinal fluid Hu, Ri and Yo antibodies were negative, and no bacteria, cryptococcus and acid-fast bacilli were found in cerebrospinal fluid smear. Cerebrospinal fluid TORCH8 items were normal, and cerebrospinal fluid oligoclonal band was negative. Both blood and cerebrospinal fluid LGI-1 antibody were positive. CT scan of the head showed no abnormal changes in the shape and density of the brain parenchyma. FDG-PET showed that the uptake of radioactivity in the right caudate nucleus and putamen was significantly increased, and the increase rate was 95% compared with the contralateral nucleus. Radioactivity uptake in the medial right temporal lobe was significantly increased, with an increase rate of 32% compared with the contralateral (Figure 1)。 Cranial MRI (plain scan + hippocampus + DWI): T₁Patchy hyperintensity was observed in the upper right basal ganglia area, and the medial right temporal lobe was slightly full, T₂/FLAIR signal is slightly higher (Figure 2)。 EEG: No epileptiform abnormal discharge was observed. Neuropsychological examination: MMSE: 23. Treatment and short-term prognosis: The patient was given clonazepam and sodium valproate anti-epileptic therapy, methylprednisolone 1 g pulse therapy for 5 days, and gamma globulin 0.4 g/kg modulated immunotherapy. Follow-up after 1 month: Memory improved significantly compared with before, and facial-brachial muscle tone (FBDS) -like symptoms disappeared.

Warfarin is mainly used for long-term anticoagulant therapy, but its therapeutic window is relatively narrow, so it needs regular and frequent monitoring and dose adjustment to maintain the efficacy and safety of warfarin therapy^[1,2]。 Long-term anticoagulation therapy with warfarin has always been a thorny problem in clinical practice. Under the traditional anticoagulation management mode, anticoagulant patients, especially those in remote areas, consume a lot of time, manpower and financial resources, have low quality of life and low anticoagulation compliance. It is difficult to maintain the international normalized ratio (INR) of anticoagulant patients at a relatively stable ideal level, which is a difficult problem in clinical application. The efficacy and safety of warfarin are closely related to its anticoagulant effect and vary widely from individual to individual, so it is necessary to closely monitor to prevent overdose or underdose. The traditional anticoagulation management mode is that anticoagulant patients regularly and frequently go to medical institutions to draw blood to detect prothrombin time, and then doctors give anticoagulation recommendations according to INR results. Manpower, financial resources, time consumption, hemorrhage, embolism and other complications are a heavy burden for patients receiving oral warfarin anticoagulation^[3]。 Finding suitable anticoagulation management mode has been a hot topic at home and abroad. This paper will introduce the anticoagulation management mode at home and abroad.

As one of the most common cancers in the world, lung cancer kills nearly 1.6 million people worldwide every year^[1]。 Among men, nearly 17% of cancer patients are lung cancer, ranking first among all types of cancer^[2]。 In China, lung cancer ranks first among new malignancies among all new cancer cases^[3]。

In recent years, a landmark change in the treatment of non-small cell lung cancer (NSCLC) is the treatment of EGFR-tyrosine kinase inhibitor (TKI) in advanced patients with positive epidermal growth factor receptor (EGFR) gene mutations. Among them, exon 19 in-frame deletion and exon 21 point mutation (L858R) are called classical mutations, accounting for 45% and 50% of EGFR mutations, respectively. Its independent risk factors include Asian, female, non-smoking and adenocarcinoma, which are effective for reversible EGFR-TKI treatment^[1]。 Other EGFR mutations, such as the 18-exon G719 point mutation (e.g., G719A, G719C, G719S) and the 21-exon L861Q mutation. Clinical studies have shown an objective response rate (ORR) of 36.8% for G719X single mutation and 50% for G719X pooled mutation for the first generation EGFR-TKI^[2]。 L861Q is partially effective for the first generation EGFR-TKI, but its sensitivity is lower than that of L858R mutation, and the second generation EGFR-TKI can effectively inhibit L861Q mutation^[3]。

fecalmicrobiota transplantation (FMT), as an important strategy for reconstitution of intestinal flora, can effectively treat recurrent Clostridium difficile infection (Clostridium difficileinfection, CDI), has also been used for exploratory treatment of a variety of other diseases associated with intestinal flora. The methodology, indications and related policies and regulations of FMT clinical application have been the focus of research in recent years. This article in 2013^[1]、2014^[2]On the basis of the continuous review of the progress of FMT in 2015, through Chinese and foreign databases such as PubMed, Wanfang, CNKI, and the reports of important conferences such as Digestive Diseases Week (DDW) in 2016, this paper comprehensively reviews the domestic and foreign progress in this field from 2015 to 2016, and looks forward to its future development trend.

senile degenerative heart valvular disease (SDHVD), also known as senile calcified heart valvular disease, or senile calcified heart syndrome. It refers to the degeneration and fibrosis of the connective tissue around the heart valve with age, and the deposition of calcium salts on the basis of lipid deposition, resulting in valve stenosis and/or insufficiency. The main clinical manifestations are calcified aortic stenosis or mitral annulus calcification (MAC). With the progress of aging in China, the prevalence of SDHVD is increasing^[1]It has become an important cause of sudden syncope, arrhythmia, heart failure and sudden death in the elderly^[2]。 MAC is one of the main manifestations of SDHVD, which often leads to mitral regurgitation and arrhythmia, and directly affects the prognosis of cardiac surgery. This article reviews the epidemiology, clinical characteristics, pathogenesis, diagnosis and treatment of MAC.